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Einarsdottir, Elisabet. "Mapping genetic diseases in northern Sweden." Doctoral thesis, Umeå universitet, Medicinsk biovetenskap, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-499.
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The population of northern Sweden has previously been shown to be well suited for the mapping of monogenic diseases. In this thesis we have tested the hypothesis that this population could also be used for efficient identification of risk genes for common diseases. In Paper I we have hypothesised that despite the admixture of Swedish, Finnish and Sami, the northern Swedish population consists of sub-populations geographically restricted by the main river valleys running through the region. This geographic isolation, in combination with founder effects and genetic drift, could represent a unique resource for genetic studies. On the other hand, it also underlines the importance of accounting for this e.g. in genetic association studies. To test this hypothesis, we studied the patterns of marriage within and between river valley regions and compared allelic frequencies of genetic markers between these regions. The tendency to find a spouse and live in the river valley where one was born is strong, and allelic frequencies of genetic markers vary significantly between adjacent regions. These data support our hypothesis that the river valleys are home to distinct sub-populations and that this is likely to affect mapping of genetic diseases in these populations. In Paper II, we tested the applicability of the population in mapping HSAN V, a monogenic disease. This disease was identified in only three consanguineous individuals suffering from a severe loss of deep pain perception and an impaired perception of heat. A genome-wide scan combined with sequencing of candidate genes resulted in the identification of a causative point mutation in the nerve growth factor beta (NGFB) gene. In Paper III, a large family with multiple members affected by familial forms of type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis (AITD) was studied. This syndrome was mapped to the IDDM12 region on 2q33, giving positive lodscores when conditioning on HLA haplotype. The linkage to HLA and to the IDDM12 region thus confirmed previous reports of linkage and/or association of T1DM and AITD to these loci and provided evidence that the same genetic factors may be mediating these diseases. This also supported the feasibility of mapping complex diseases in northern Sweden by the use of familial forms of these diseases. In Paper IV, we applied the same approach to study type 2 diabetes mellitus (T2DM). A non-parametric genome-wide scan was carried out on a family material from northern Sweden, and linkage was found to the calpain-10 locus, a previously described T2DM-susceptibility gene on 2q37. Together, these findings demonstrate that selecting for familial forms of even complex diseases, and choosing families from the same geographical region can efficiently reduce the genetic heterogeneity of the disease and facilitate the identification of risk genes for the disease.
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Einarsdóttir, Elísabet. "Mapping genetic diseases in northern Sweden." Umeå : Department of Medical Biosciences, Umeå University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-499.
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Guo, Youling, and 郭友玲. "Genetic and genomic mapping of common diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B50533861.
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Genome-wide mapping of susceptibility genes was conducted in two complex disorders of hypertension and epilepsy, allowing the dissection of the genetic architecture of these common diseases and related quantitative traits. The study performed comprehensive genetic analyses in a genome-wide scale, using different structure of data – sib-pairs and case-control samples.
To identify genes influencing hypertension and blood pressure, a combined linkage and association study was conducted using over half a million SNPs genotyped in 328 siblings. Regions of significant linkage were identified for blood pressure traits on chromosomes 2q22.3 and 5p13.2, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P < 7 10-5) for hypertension. One candidate gene, PDC, was replicated in the family-based association tests.
A two-stage genome-wide association study (GWAS) was performed in a total of 1,087 cases and 3,444 controls, to identify common susceptibility variants of epilepsy in Chinese. The combined analysis identified two association signals in CAMSAP1L1, rs2292096 [G] (P=1.0×10-8, OR =0.63) and rs6660197 [T] (P=9.9×10-7, OR=0.69), which are highly correlated, achieving genome-wide significance. One SNP (rs9390754, P = 1.7 × 10-5) in GRIK2 was refined as a previously-implicated association. In addition to SNPs, the assessment of CNVs in GWAS was performed, which could provide valuable clues to discover genes contributing to the heritability of epilepsy. A genome-wide scan for epilepsy through the use of DNA pooling also provides an alternative approach to reducing the substantial cost and thus increase efficiency in large-scale genetic association studies.
The genome-wide mapping studies in families and unrelated individuals are complementary and together offer a comprehensive catalog of common variations and structural variants implicated for both quantitative and qualitative traits.published_or_final_version
Psychiatry
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Doctor of Philosophy
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O'Connell, Jeffrey R. "Algorithms for linkage analysis, error detection and haplotyping in pedigrees." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325622.
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Prokunina, Ludmila. "Strategies for Identification of Susceptibility Genes in Complex Autoimmune Diseases." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4138.
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Standing, A. S. I. "Genetic mapping for the discovery of novel genes causing autoinflammatory diseases." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1417187/.
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The autoinflammatory syndromes are an emerging group of diseases, some with defined genetic cause, characterised by seemingly unprovoked inflammation which derives from a disruption of innate immunity. Novel as yet undefined syndromes are increasingly recognised in consanguineous families who may have normal parents and both affected and unaffected offspring. This type of family is ideal for genetic mapping as both copies of the (presumed recessive) disease causing alleles are likely to have originated in a recent shared common ancestor, and may be linked with markers which will be homozygous in the affected children. In this thesis affected and unaffected offspring and parents in three first-cousin Pakistani families were genotyped with Illumina 610 SNP arrays. This data was used for homozygosity mapping and parametric multipoint linkage analysis. For the first family, a 5Mb region was identified from this mapping. Candidate genes were chosen by members of an expert panel and the exons of these genes were Sanger sequenced. DNA from the entire homozygous region linked to the disease locus (5Mb) was captured using a custom designed 385k array from Nimblegen and then resequenced using the Illumina Genome Analyser II, revealing over 50 coding change variants. These entered a filtering process involving: the selection of rare variants and screening of extended family members, ethnically matched controls and disease controls, and the exclusion of unlikely candidates. This ultimately identified two missense variants of interest in two genes in family A, a novel variant in MEFV the gene affected in Familial Mediterranean Fever, and a variant in TNF Receptor Associated Protein 1 gene TRAP1. The potential contribution of disrupting of the function of these genes to the pathogenesis was assessed using siRNA knockdown in HeLa and THP1 cells. Outcomes assessed include levels of reactive oxygen species (ROS), which are central to many inflammatory processes, and cytokine production. This suggested that TRAP1 may be involved through elevated ROS and TNFα secretion.
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Ramburan, Viresh Premraj. "Genetic mapping of adult plant stripe rust resistance in the wheat cultivar Kariega." Thesis, Stellenbosch : Stellenbosch University, 2003. http://hdl.handle.net/10019.1/53438.
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Thesis (PhD (Agric)) -- Stellenbosch University, 2003.ENGLISH ABSTRACT: Stripe (yellow) rust of wheat, caused by Puccinia striiformis f.sp. tritici, was first detected as a single introduction into South Africa in 1996. Two additional pathotypes have since been identified. Control of the disease may be achieved by use of genetic adult plant resistance (APR) as is present in the local cultivar 'Kariega'. The aim of this project was to understand the genetic basis of the APR in 'Kariega' to facilitate breeding of new varieties with genetic resistance to stripe rust. A partial linkage map of a 'Kariega X Avocet S' doubled haploid population covering all 21 wheat chromosomes was generated using 208 DNA markers, viz, 62 SSR, 133 AFLP, 3 RGA and 10 SRAP markers, and 4 alternative loci. The different marker techniques detected varying polymorphism, viz, overall SSR: 46%, AFLP: 7%, SRAP: 6% and RGA: 9%, and the markers produced low levels of missing data (4%) and segregation distortion (5%). A significant feature of the linkage map was the low polymorphism found in the D genome, viz, 19% of all mapped DNA markers, 11% of all AFLP markers and 30% of the total genome map distance. A region exhibiting significant segregation distortion was mapped to chromosome 4A and a seedling resistance gene for stem rust (Puccinia graminis f.sp . tritici), Sr26, mapped to chromosome 6A close to three SSR markers. The leaf tip necrosis gene, Ltn, which was also segregating in the population, mapped to chromosome 7D. Protocols for SRAP and RGA were optimised, and SRAP marker use in wheat genetic linkage studies is reported for the first time. The linkage map was used together with growth chamber and replicated field disease scores for QTL mapping. Chromosomes showing statistically significant QTL effects were then targeted with supplementary SSR markers for higher resolution mapping. The quality of disease resistance phenotypic data was confirmed by correlation analysis between the different scorers for reaction type (0.799±0.023) and for transformed percentage leaf area infected (0.942±0.007). Major QTL were consistently identified on chromosome 7D (explaining some 25-48% of the variation) and on chromosome 2B (21-46%) using transformed percentage leaf area infected and transformed reaction type scores (early and final) with interval mapping and modified interval mapping techniques. Both chromosomal regions have previously been identified in other studies and the 7D QTL is thought likely to be the previously mapped APR gene Yr 18. Minor QTL were identified on chromosomes lA and 4A with the QTL on 4A being more prominent at the early field scoring for both score types. A QTL evidently originating from 'Avocet S' was detected under growth chamber conditions but was not detected in the field, suggesting genotype-environment interaction and highlighting the need for modifications of growth chamber conditions to better simulate conditions in the field. The genetic basis of the APR to stripe rust exhibited by 'Kariega' was established by mapping of QTL controlling this trait. The linkage map constructed will be a valuable resource for future genetic studies and provides a facility for mapping other polymorphic traits in the parents of this population with a considerable saving in costs.
AFRIKAANSE OPSOMMING: Streep of geelroes van koring word veroorsaak deur Puccinia striiformis f. sp tritici, en is die eerste keer in 1996 in Suid-Afrika na introduksie van 'n enkele patotipe waargeneem. Twee verdere patotipes is sedertdien in Suid-Afrika gei"dentifiseer. Beheer van die siekte word veral moontlik gemaak deur die gebruik van genetiese volwasseplantweerstand soos gei"dentifiseer in die plaaslike kultivar 'Kariega'. Die doel van hierdie studie was om die genetiese grondslag van die streeproesweerstand te ontrafel ten einde die teling van nuwe bestande kultivars moontlik te maak. 'n Verdubbelde haplo1ede populasie uit die kruising 'Kariega X Avocet S' is aangewend om 'n gedeeltelike koppelingskaart vir die volle stel van 21 koring chromosome saam te stel. Die kaart het uit 208 DNA merkers, nl., 62 SSR, 133 AFLP, 3 RGA, 10 SRAP merkers en 4 ander lokusse bestaan. Totale polimorfisme wat deur die verskillende merkersisteme opgespoor is, was as volg: SSR: 46%, RGA: 9%, AFLP: 7% en SRAP: 6%. Die mate van ontbrekende data was gering (4%) asook die mate van segregasie distorsie (5%) van 'n enkele geval wat op chromosoom 4A gekarteer is. 'n Prominente kenmerk van die koppelingskaart is die relatiewe gebrek aan polimorfiese merkers op die D-genoom, nl., slegs 19% van alle DNA merkers en 11% van alle AFLP merkers wat slegs 30% van die totale genoom kaartafstand bestaan het. Die stamroes (Puccinia graminis f. sp. tritici) saailingweerstandsgeen, Sr26, karteer op chromosoom 6A naby drie SSR merkers. Die geen vir blaartipnekrose, Ltn, karteer op chromosoom 7D. Protokolle vir SRAP en RGA merkers is ge-optimiseer en gebruik van SRAP merkers in koppelings-analise word vir die eerste keer in koring gerapporteer. Die koppelingskaart is in kombinasie met groeikamerdata en gerepliseerde veldproefdata gebruik om die gene (QTL) vir volwasseplant streeproesweerstand te karteer. Chromosome met statisties betekenisvolle QTL is met aanvullende SSR merkers geteiken om die resolusie van kartering verder te verhoog. Die kwaliteit van fenotipiese data, soos in die proewe aangeteken, is bevestig deur korrelasies te bereken tussen lesings geneem deur onafhanklike plantpataloe (0.799 ± 0.023 vir reaksietipe en 0.942 ± 0.007 vir getransformeerde persentasie blaaroppervlakte besmet). Hoofeffek QTL vir die twee maatstawwe van weerstand is deur middel van die metodes van interval QTL kartering en gemodifiseerde interval QTL kartering konsekwent op chromosome 7D (25-48% van variasie verklaar) en 2B (21-46% van variasie verklaar) ge"identifiseer. In vorige studies is aangetoon dat beide chromosome 7D en 2B QTL vir volwasseplant streeproesweerstand dra. Die 7D QTL is waarskynlik die weerstandsgeen, Yr 18. QTL met klein effekte op weerstand is op chromosome lA en 4A ge"identifiseer. Die effek van laasgenoemde geen was meer prominent in die velddata in die vroee datum van weerstandsbeoordeling. Een QTL, afkomstig van 'Avocet S', is slegs onder groeikamertoestande identifiseerbaar. Dit dui op moontlike genotipe-omgewing wisselwerking en beklemtoon die noodsaaklikheid om aanpassings te maak in groeikamertoestande vir beter simulasie van veldproeftoestande. Die genetiese grondslag van volwasseplantweerstand teen streeproes in die kultivar 'Kariega' is deur QTL kartering bepaal. Die 'Kariega X Avocet S' koppelingskaart kan as 'n waardevolle basis dien vir toekomstige genetiese ontledings van ander polimorfiese kenmerke in die populasie.
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Bell, Martyn V. "A physical analysis of the fragile X (FRAXA) region in man." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302861.
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Schramm, Heather Elizabeth. "Development of mapping by admixture linkage disequilibrium for understanding human complex genetic diseases /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
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Bierman, Anandi. "Mapping and survey sequencing of Dn resistance genes in Triticum aestivum L." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96912.
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Thesis (PhD)--Stellenbosch University, 2015ENGLISH ABSTRACT : Diuraphis noxia Kurdjumov (Russian Wheat Aphid; RWA) is a pest of wheat and barley that has spread from its home range in the fertile crescent to most wheat producing countries except Australia. Since its first introduction to South Africa and the USA in the late 20th century, breeding programs for wheat phenotypes resistant to the aphid were put in place. Conventional breeding practices rely on phenotypic screening to verify traits carried by offspring and genetic tools such as marker assisted selection (MAS) have greatly aided this process in speed and accuracy. The size and complexity of the wheat genome, its allopolyploid nature and repetitive elements have, however, posed a challenge to studies on the genetics of this cereal crop. Many studies have focused on chromosome 3B which is the largest of the wheat chromosomes and easily separated from the redundant genomic background by techniques such as flow cytometry. The similarity in size of the remaining chromosomes however, limits the application of flow cytometry to their isolation. Databases such as Grain-Genes (http://wheat.pw.usda.gov/GG2/index.shtml) house marker data from various mapping studies for all wheat chromosomes and in 2014 the International Wheat Genome Sequencing Consortium (IWGSC) completed the draft genome sequence of wheat categorized by chromosome. Sources of resistance (Dn resistance genes) against RWA are located on chromosome 7D. but despite the marker and sequence data available currently, mapping studies specific for the Dn resistance genes are few. Additionally, sequence data available is derived from cultivars susceptible to RWA and is not comprehensively annotated and assembled in many cases. In this study, we demonstrate a novel, combined approach to isolate and characterize the Dn resistance genes through the use of a genetic map constructed from Amplified Fragment Length Polymorphism (AFLP), Expressed Sequence Tag (EST) and microsatellite markers and a physical map constructed from Next Generation Sequencing (NGS) data of ditelosomic chromosomes (7DS and 7DL) isolated by microdissection on the PALM microbeam system. A 122.8 cM genetic map was produced from 38 polymorphic AFLP markers and two ESTs with the microsatellite Xgwm111 as anchor to related genetic maps. Through comparison to maps available on GrainGenes the location of the Dn1 resistance gene was narrowed down to a deletion bin (7DS5-0.36-0.62) on the short arm of chromosome 7D with an AFLP marker (E-ACT/M-CTG_0270.84) mapping closely at 3.5 cM and two ESTs mapping at 15.3 cM and 15.9 cM from Dn1. Isolation of individual chromosome arms 7DS and 7DL using the PALM Microbeam system allowed sequencing of the chromosome without the redundancy of the remainder of the hexaploid genome. Through isolating the chromosome arms in this way, a >80-fold reduction in genome size was achieved as well as a major reduction in repetitive elements. Analysis of the sequencing data confirmed that 7DL is the physically shorter arm of the chromosome though it contains the majority of protein coding sequences.
AFRIKAANSE OPSOMMING : Diuraphis noxia Kurdjumov (Russiese koring-luis; RWA) is « pes wat op koring en gars voorkom. Die pes het vanaf sy tuiste in die midde Ooste na meeste koringproduserende lande behalwe Australië versprei. Sedert die eerste bekendstelling van RWA in Suid Afrika en die VSA in die vroeë 20ste eeu is teelprogramme ten gunste van koring lyne met weerstand teen RWA begin. Tradisionele teelprogramme maak op fisieise observasie van die fenotipe staat om te verifieer of plante in die nageslag die gewenste eienskap dra. Genetiese metodes soos merkerondersteunde seleksie (MAS) versnel hierdie selekteringsproses grootliks. Die grootte en kompleksiteit van die koring genoom asook die polyploïde en herhalende natuur daarvan is « groot hindernis vir genetiese studies van hierdie graangewas. Baie studies het op chromosoom 3B gefokus wat die grootste van die koring chromosome is en dus maklik vanaf die res van die oorbodige genomiese agtergond deur tegnieke soos vloeisitometrie geskei word. Die ooreenkoms in grootte tussen die res van die chromosome bemoeilik die toepassing van vloeisitometrie om hulle te isoleer. Databasisse soos GrainGenes (http://wheat.pw.usda.gov/GG2/index.shtml) bevat merker data vanaf verskeie karterings-studies vir al die chromosome en in 2014 het die "International Wheat Genome Sequencing Consortium"(IWGSC) die voorlopige basispaarvolgorde van die koring genoom bekendgestel, gekategoriseer volgens chromosoom. Weerstandsbronne (Dn weerstandsgene) teen RWA kom meestal op chromosoom 7D voor. Ten spyte van merker en basispaarvolgorde data tans beskikbaar is karterings-studies spesifiek tot die Dn gene skaars en basispaarvolgorde data is vanaf kultivars afkomstig wat nie weerstandbiedend teen RWA is nie en waarvan die annotasie en samestelling baie keer nie goed is nie. In hierdie studie demonstreer ons « nuwe, gekombineerde aanslag om die Dn weerstandsgene te isoleer en karakteriseer deur van « genetiese kaart opgestel met "Amplified Fragment Length Polymorphism"(AFLP), "Expressed Sequence Tag"(EST) en mikrosatelliet merkers asook « fisiese kaart saamgestel deur die volgende-generasiebasispaarvolgordebepaling van ditelosomiese chromosome (7DS en 7DL) geïsoleer deur mikrodisseksie met die "PALM Microbeam"sisteem gebruik te maak. « Genetiese kaart van 122.8 cM was met 38 polimorfiese AFLP merkers en twee EST merkers geskep. Die mikrosatelliet, Xgwm111, is ook ingesluit en het as anker vir verwante genetiese-kaarte gedien. Deur vergelyking met genetiese-kaarte op GrainGenes is die posisie van die Dn1 weerstandsgeen vernou na « delesie bin (7DS5-0.36-0.62) op die kort arm van chromosoom 7D met « AFLP merker (EACT/ M-CTG_0270.84) wat ongeveer 3.5 cM vanaf die geen karteer. Die twee EST merkers is 15.3 cM en 15.9 cM vanaf die geen gekarteer. Isolering van die individuele chromosoom arms, 7DS en 7DL, deur van die "PALM Microbeam"sisteem gebruik te maak het basispaarvolgordebepaling van die chromosoom toegelaat sonder die oortolligheid van die res van die hexaploïde genoom. Deur die chromosoom so te isoleer is « >80-maal verkleining in genoom grootte bereik insluitend « groot reduksie in herhalende elemente. Analise van die data vanaf basispaarvolgordebepaling het bevestig dat chromosoom 7D die fisiese kleiner chromosoom is maar dat dit die meerderheid van proteïn koderende basispaarvolgordes bevat.
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Phipps, Maude Elvira. "The physical mapping of chromosome 3p25-26 : a region involved in Von Hippel-Lindau disease and chromosome 3p deletion syndrome." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336776.
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Shrestha, Roshi. "A physiological and genetic mapping study of tolerance to root-knot nematode in rice." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=24807.
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Graham, Jinko. "Disequilibrium fine-mapping of a rare allele via coalescent models of gene ancestry /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/9568.
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Qianren, Jin. "Search for susceptibility loci and candidate genes for breast cancer /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-030-3/.
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Sharma, Sapna. "Genetics of Wheat Domestication and Septoria Nodorum Blotch Susceptibility in Wheat." Thesis, North Dakota State University, 2019. https://hdl.handle.net/10365/29767.
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T. aestivum ssp. spelta Iranian type has long been thought to potentially be the direct non-free threshing hexaploid progenitor. I evaluated a RIL population derived from a cross between CS and Iranian spelta accession P503 to identify loci suppressing free-threshabilty in P503. Identification of QTL associated with threshability in region known to harbor the Tg2A gene, and an inactive tg2D allele supported the hypothesis of Iranian spelta being derived from a more recent hybridization between free-threshing hexaploid and emmer wheat. Parastagonospora nodorum is an important fungal pathogen and secretes necrotrophic effectors that evoke cell death. In this research, a DH population segregating for Snn5 was used to saturate Snn5 region of chromosome 4B with molecular markers. The physical distance between Snn5 flanking markers was narrowed to 1.38 Mb with genetic distance of 2.8 cM. The markers developed in this study will provide a strong foundation for map-based cloning of Snn5.
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Van, Zyl Sonet. "Inheritance and genetic mapping of Xiphinema index resistance derived from Vitis arizonica." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71823.
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Thesis (PhD(Agric))--Stellenbosch University, 2012.ENGLISH ABSTRACT: Grapevines are one of the most important and diverse crops in the world, but tend to be susceptible for numerous pests and diseases. The dagger nematode, Xiphinema index (X. index) is a well-known soil-borne pest of grapevine and vector of grapevine fanleaf virus. Several Vitis species showed resistance to this pest. Breeding efforts have been underway for several decades to create resistant rootstocks. However, conventional breeding efforts are time consuming due to grapevines being a perennial crop, its heterozygosity, as well as its long growth cycle. Breeding new grapevine varieties are also expensive and work intensive. The development of marker-assisted selection introduced a way to overcome some of the abovementioned problems. The aim of this study was to broaden the genetic evaluation and breeding efforts for improved X. index resistance in grapevine rootstocks. In 2007 several crosses were made in the University of California, Davis vineyards. The background for all these crosses consisted of V. arizonica. These V. arizonica plants are part of a collection obtained by H.P. Olmo during the 1960’s. In recent studies it was established that X. index resistance is controlled by a single dominant gene. The 0701 (R8916-07 (Wichita Refuge x b40-14) x R8916-32), 0704 (161-49C x b40-14) and 0705 (161-49C x R8916-22) populations were created to confirm the homozygous nature of b40-14, a V. arizonica accession. In addition, several V. arizonica species were screened to confirm their resistance or susceptibility towards X. index feeding. The 0705 population was also used to create a genetic map for X. index resistance. In this study a new and improved screening method was developed to inoculate vines under greenhouse conditions. This screening method proved to be quicker and less damaging on the nematodes than traditional systems. Control varieties were used and O39-16, a commercial rootstock showed no damage, even with high nematode pressure, whereas V. rupestris Saint George had severe root damage and decline after eight weeks of exposure. A range of V. arizonica accessions was tested for their resistance to X. index feeding. Of the 18 genotypes tested, half showed resistance and the rest were susceptible. It is possible that these genotypes are not pure V. arizonica genotypes. Genotypes with V. arizonica in the background were also tested. Wichita Refuge was used as a susceptible female parent and the progeny were expected to be heterozygous resistant. Some of the progeny allowed low levels of feeding damage, which may have been the result of the more effective inoculation method described above. The 0701 population confirmed the hypothesized model of 3:1 (Resistance (R):Susceptible (S)) segregation although 13 of the genotypes showed significantly higher gall numbers than the susceptible female parent. The possibility of transgressive segregation exists, but needs to be confirmed. All progeny from the 0704 population should be heterozygous resistant, but a 1:1 (R:S) segregation pattern was observed. The 0705 population was created as a mapping population to study X. index resistance. This population was also tested in the greenhouse for its X. index resistance and was expected to segregate 1:1 (R:S). The X2 analysis did not fully support this model. A genetic map covering all 19 linkage groups, and positioning 175 polymorphic SSR markers was created for the 164 progeny in the 0705 population. MapQTL analysis revealed a major QTL on linkage group 9 and two minor QTL’s on groups 13 and 19. The major QTL placed between markers VMC1c10 and CTG1032918 with a LOD score of 33.4 explaining 70.5% of the phenotypic variance for X. index. This QTL is the second major QTL discovered for X. index resistance. With the discovery of a second major QTL, the two types of resistance can be pyramided. Work is underway to saturate the area around the major QTL on linkage group 9 and to move towards physical mapping of X. index resistance. The b40-14 V. arizonica accession is also known for its resistance to Pierce’s disease and the possibility of simultaneous expression of two types of resistance is created. The 0705 population can also be used to evaluate phenotypical characteristics in the field to determine if useful rootstocks can be selected. Taken together, the results obtained in this study provide improved methods and highly characterized plant populations to support the efforts in obtaining improved X. index resistance in grapevine rootstocks.
AFRIKAANSE OPSOMMING: Wingerde is van die belangrikste en mees diverse gewasse op aarde, maar hulle neig om vir ‘n verskeidenheid plae en siektes vatbaar te wees. Die dolk-aalwurm, Xiphinema index (X. index), is ‘n bekende grondgedraagde plaag van wingerd en ‘n vektor vir wingerd- netelblaarvirus. Verskeie Vitis-spesies toon weerstand teen hierdie plaag. Daar word reeds vir dekades pogings aangewend om weerstandbiedende onderstokke te kweek. Konvensionele kweekpogings is egter tydrowend omdat wingerd ‘n meerjarige gewas is, op grond van die heterosigositeit van die gewas, sowel as die lang groeisiklus. Dit is ook duur en arbeidsintensief om nuwe wingerdvariëteite te kweek. Die ontwikkeling van merkerondersteunde seleksie het dus ‘n metode verskaf om sommige van bogenoemde probleme te oorkom. Die doelwit van hierdie studie was om die genetiese evaluerings- en kweekpogings vir verbeterde X. index-weerstand in wingerd-onderstokke te verbreed. In 2007 is verskeie kruisings in die wingerde by die Universiteit van Kalifornië, Davis gemaak. Die agtergrond vir al hierdie kruisings het bestaan uit V. arizonica. Hierdie V. arizonica-plante vorm deel van ‘n versameling wat in die 1960’s deur H.P. Olmo verkry is. In onlangse studies is daar bepaal dat X. index-weerstand deur ‘n enkele dominante geen beheer word. Die 0701 (R8916-07 (Wichita Refuge x b40-14) x R8916-32), 0704 (161-49C x b40-14) en 0705 (161-49C x R8916-22) bevolkings is geskep om die homosigotiese geaardheid van b40-14, ’n V. arizonicaafstammeling, te bevestig. Daarbenewens is verskeie V. arizonica-spesies gesif om hulle weerstand teen of vatbaarheid vir X. index voeding te bevestig. Die 0705 bevolking is ook gebruik om ‘n genetiese kaart vir X. indexweerstand te skep. In hierdie studie is ‘n nuwe en verbeterde siftingsmetode ontwikkel om wingerdstokke onder glashuistoestande te inokuleer. Daar is gewys dat hierdie siftingsmetode vinniger en minder skadelik vir die aalwurms as tradisionele metodes is. Beheervariëteite is gebruik en O39-16, ‘n kommersiële onderstok, het geen skade getoon nie, selfs met hoë aalwurmdruk, terwyl V. rupestris Saint George ernstige wortelskade en agteruitgang na agt weke se blootstelling getoon het. ‘n Verskeidenheid V. arizonica-afstammelinge is vir hulle weerstand teen X. index-voeding getoets. Van die 18 genotipes wat getoets is, het die helfte weerstand getoon en die res was vatbaar. Dit is moontlik dat hierdie genotipes nie suiwer V. arizonica-genotipes was nie. Genotipes met V. arizonica in hulle agtergrond is ook getoets. Wichita Refuge is as ‘n vatbare vroulike ouer gebruik en die verwagting was dat die nageslag heterosigoties weerstandbiedend sou wees. Sommige van die nageslag het lae vlakke van voedingskade toegelaat, wat moontlik die gevolg was van die meer doeltreffende inokulasiemetode wat hierbo beskryf word. Die 0701 bevolking het die veronderstelde model van 3:1 (Weerstandbiedend (W):Vatbaar (V)) segregasie bevestig, hoewel 13 van die genotipe noemenswaardig hoër galgetalle as die vatbare vroulike ouer getoon het. Die moontlikheid van transgressiewe segregasie bestaan, maar dit moet nog bevestig word. Alle nageslag van die 0704 bevolking behoort heterosigoties weerstandbiedend te wees, maar ‘n 1:1 (W:V) segregasiepatroon is waargeneem. Die 0705 bevolking is as ‘n karteringsbevolking geskep om X. index-weerstand te bestudeer. Hierdie bevolking is ook in die glashuis vir sy X. index-weerstand getoets en daar is verwag dat dit 1:1 (W:V) sou segregeer. Die X2 analise het nie hierdie model ten volle ondersteun nie. ‘n Genetiese padkaart wat al 19 skakelingsgroepe en die posisies van 175 polimorfiese SSR merkers toon, is vir die 164 afstammelinge in die 0705 bevolking geskep. MapQTL analise het ‘n groot kwantitatiewe eienskap lokus (QTL) op skakelingsgroep 9 en twee kleiner QTL’e op groepe 13 en 19 onthul. Die groot QTL is tussen merkers VMC1c10 en CTG1032918 met ‘n LOD telling van 33.4 geplaas en het 70.5% van die fenotipiese variansie van X. index verklaar. Hierdie QTL is die tweede groot QTL wat vir X. index-weerstand ontdek is. Met die ontdekking van ‘n tweede groot QTL, kan die twee soorte weerstand gepiramideer word. Werk word reeds onderneem om die area rondom die groot QTL op skakelingsgroep 9 te versadig en om na die fisiese kartering van X. index-weerstand te beweeg. Die b40-14 V. arizonica-afstammeling is ook bekend vir sy weerstand teen Pierce se siekte en die moontlikheid word geskep vir die gelyktydige uitdrukking van twee soorte weerstand. Die 0705 bevolking kan ook gebruik word om die fenotipiese kenmerke in die veld te evalueer om te bepaal of bruikbare onderstokke geselekteer kan word. In kombinasie behoort die resultate wat in hierdie studie verkry is, verbeterde metodes en hoogs gekarakteriseerde plantbevolkings te lewer wat die pogings sal ondersteun om verbeterde X. index-weerstand in wingerdonderstokke te verkry.
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Veereshlingam, Harita. "Characterization of Infection Arrest Mutants of Medicago Truncatula and Genetic Mapping of Their Respective Genes." Thesis, University of North Texas, 2005. https://digital.library.unt.edu/ark:/67531/metadc5567/.
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In response to compatible rhizobia, leguminous plants develop unique plant organs, root nodules, in which rhizobia fix nitrogen into ammonia. During nodule invasion, the rhizobia gain access to newly divided cells, the nodule primordia, in the root inner cortex through plant-derived cellulose tubes called infection threads. Infection threads begin in curled root hairs and bring rhizobia into the root crossing several cell layers in the process. Ultimately the rhizobia are deposited within nodule primordium cells through a process resembling endocytosis. Plant host mechanisms underlying the formation and regulation of the invasion process are not understood. To identify and clone plant genes required for nodule invasion, recent efforts have focused on Medicago truncatula. In a collaborative effort the nodulation defect in the lin (lumpy infections) mutant was characterized. From an EMS-mutagenized population of M. truncatula, two non-allelic mutants nip (numerous infections with polyphenolics) and sli (sluggish infections) were identified with defects in nodule invasion. Infection threads were found to proliferate abnormally in the nip mutant nodules with only very rare deposition of rhizobia within plant host cells. nip nodules were found to accumulate polyphenolic compounds, indicative of a host defense response. Interestingly, nip was also found to have defective lateral root elongation suggesting that NIP has a role in both nodule and lateral root development. NIP was found to map at the upper arm of chromosome 1. In sli, infection threads were observed to bring rhizobia from infection threads to newly divided nodule primordium cells in the roots inner cortex. Polyphenolic accumulation in sli nodule/bumps was found. Lateral roots in sli were found to be clustered at the top of the root, indicating that sli like nip may be defective in lateral root development.
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Adeyanju, Adedayo. "Genetic study of resistance to charcoal rot and Fusarium stalk rot diseases of sorghum." Diss., Kansas State University, 2014. http://hdl.handle.net/2097/17559.
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Doctor of PhilosophyDepartment of Agronomy
Tesfaye Tesso
Fusarium stalk rot and charcoal rot caused by Fusarium thapsinum and Macrophomina phaseolina respectively are devastating global diseases in sorghum that lead to severe quality and yield loss each year. In this study, three sets of interrelated experiments were conducted that will potentially lead to the development of resistance based control option to these diseases. The first experiment was aimed at identifying sources of resistance to infection by M. phaseolina and F. thapsinum in a diverse panel of 300 sorghum genotypes. The genotypes were evaluated in three environments following artificial inoculation. Out of a total of 300 genotypes evaluated, 95 genotypes were found to have resistance to M. phaseolina and 77 to F. thapsinum of which 53 genotypes were resistant to both pathogens. In the second experiment, a set of 79,132 single nucleotide polymorphisms (SNPs) markers were used in an association study to identify genomic regions underlying stalk rot resistance using a multi-locus mixed model association mapping approach. We identified 14 loci associated with stalk rot and a set of candidate genes that appear to be involved in connected functions controlling plant defense response to stalk rot resistance. The associated SNPs accounted for 19-30% of phenotypic variation observed within and across environments. An analysis of associated allele frequencies within the major sorghum subpopulations revealed enrichment for resistant alleles in the durra and caudatum subpopulations compared with other subpopulations. The findings suggest a complicated molecular mechanism of resistance to stalk rots. The objective of the third experiment was to determine the functional relationship between stay-green trait, leaf dhurrin and soluble sugar levels and resistance to stalk rot diseases. Fourteen genotypic groups derived from a Tx642 × Tx7000 RIL population carrying combinations of stay-green quantitative trait loci were evaluated under three environments in four replications. The stg QTL had variable effects on stalk rot disease. Genotypes carrying stg1, stg3, stg1,3 and stg1,2,3,4 expressed good levels of resistance to M. phaseolina but the combination of stg1 and stg3 was required to express the same level of resistance to F. thapsinum. Other stg QTL blocks such as stg2 and stg4 did not have any impact on stalk rot resistance caused by both pathogens. There were no significant correlations between leaf dhurrin, soluble sugar concentration, and resistance to any of the pathogens.
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Hollis-Moffatt, Jade Elissa, and n/a. "Fine mapping and characterisation of an autoimmune diabetes locus, insulin dependent diabetes 21, (Idd21) on mouse chromosome-18." University of Otago. Department of Biochemistry, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070130.151657.
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Autoimmune disease is comprised of a wide variety of disorders characterised by a loss of self-tolerance towards a target organ or systemic region leading to its eventual destruction. Type 1 diabetes (T1D), autoimmune thyroid disease (AITD) and inflammatory bowel disease (IBD) are debilitating organ-specific disorders. These disorders arise from a combination of genetic factors and environmental triggers. A greater level of basic understanding of these disorders is required to delay and/or prevent their effects. Numerous autoimmune susceptibility loci have been implicated in the development of these disorders, but only a few causative genes have been identified. The aim of this project was to use comparative mapping between the human and mouse genomes to provide a greater understanding of the human autoimmune susceptibility locus, IDDM6, shown to be involved in a number of autoimmune disease conditions.
Hall et al., (2003) previously demonstrated that the mouse autoimmune diabetes locus, Idd21, on distal mouse chr18 contains orthology to human IDDM6, IDDM10, IDDM18 and rat Iddm3. As part of this project the Idd21 locus was fine mapped using the congenic mapping technique. Beginning with the consomic mouse strain, NOD.ABHChr18 (90Mb of Biozzi/ABH-derived diabetes-resistant chr18 introgressed onto a non-obese diabetic (NOD) genetic background), 13 NOD.ABHIdd21 congenic mouse strains were established. The diabetes incidences of these congenic mouse strains were statistically compared stepwise along mouse chr18 and Idd21 was fine mapped to at least four independent autoimmune diabetes loci. Idd21.1 and Idd21.2 were located on distal mouse chr18 in regions orthologous to human IDDM6 and rat Iddm3 and Idd21.3a/b and Idd21.4 were located on proximal mouse chr18 in regions orthologous to human IDDM18 and IDDM10 respectively. Candidate genes of notable interest include Map3k8, Spink5, Cd14, Dcc, Smad4 and 7, Miz1, Nfatc1 and Cd226.
Idd21.1 was further fine mapped. Beginning with the NOD.ABHD18Mit8-D18Mit214[(75-85.1Mb)] (Idd21.1) congenic strain (containing at least 10.1Mb of distal chr18 Biozzi/ABH diabetes-resistant DNA introgressed onto a NOD genetic background), seven subcongenic mouse strains were created. The diabetes incidence of these subcongenic mouse strains were statistically compared stepwise along mouse chr18 and Idd21.1 was fine mapped to at least three independent autoimmune diabetes loci; Idd21.11 (72.6-76.1Mb), Idd21.12a/b (75-76.1Mb and 80.6-81.4Mb) and Idd21.13 (84.8-85.1Mb). Candidate genes of interest in these regions include Dcc, Smad4 and 7, Miz1, Nfatc1, and Cd226.
Functional characterisation of the Idd21.1 locus was performed by adoptively transferring splenocytes from female NOD or NOD.ABHIdd21.1 mice into cohorts of severe combined immune deficient (scid) female mice, NOD/LtSz.Prkdc[scid] and NOD/LtSz.Prkdc[scid].ABHIdd21.1. There were two notable findings from this work. Firstly, NOD.ABHIdd21.1 splenocytes are not as effective as NOD at transferring diabetes to either NOD/LtSz.Prkdc[scid] (P = 0.0004) or NOD/LtSz.Prkdc[scid].ABHIdd21.1 (P = 0.0178), suggesting that Idd21.1 acquired immune cells are not as diabetogenic as NOD. Secondly, NOD/LtSz.Prkdc[scid].ABHIdd21.1 mice are more resistant to autoimmune attack than NOD/LtSz.Prkdc[scid] when injected with either NOD (P = 0.0015) or NOD.ABHIdd21.1 splenocytes (P = 0.0014), suggesting that Idd21.1 either acts by altering the intrinsic resistance of beta-cells to autoimmune attack or due to changes in the innate immune system.
Other NOD-based models of autoimmune disease, spontaneous and experimental autoimmune thyroiditis and spontaneous colitis, were also investigated to determine whether Idd21.1 is a common autoimmune disease locus. When bred onto the NOD.Cg-H2[h4] (thyroiditis model) genetic background Idd21.1 was demonstrated to increase the development of thyroiditis and reduce the incidence of insulitis in spontaneous (untreated) but not experimental (NaI-induced) NOD.Cg-H2[h4] mice. When bred onto the NOD.Cg-Il10[tm1Cgn] (colitis) genetic background Idd21.1 was demonstrated to inhibit the development of rectal prolapse in breeding female NOD.Cg-Il10[tm1Cgn] mice.
Data from this thesis demonstrate that the IDDM6 orthologous region in mouse, Idd21.1, contains several loci that influence autoimmune diabetes, thyroiditis and colitis in NOD-based mouse models. These findings are consistent with previous knowledge that IDDM6 is a common autoimmune susceptibility locus.
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Aryamanesh, Nader. "Chickpea improvement through genetic analysis and quantitative trait locus (QTL) mapping of ascochyta blight resistence using wild Cicer species /." Connect to this title, 2007. http://theses.library.uwa.edu.au/adt-WU2008.0072.
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Fry, Andrew E. "Genome mapping of malaria resistance genes : the host ligands of PfEMP1." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:df1ffe4b-ba67-4fc6-9024-b278b887d4f9.
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Erythrocytes infected by mature forms of the Plasmodium falciparum parasite adhere to other components of the vascular space, a behavior considered critical to the pathogenesis of severe malaria. Adhesion is mediated by the P. falciparum erythrocyte membrane protein 1 (PfEMP1), a highly variant antigen expressed by the parasite and subject to switching during the course of an infection. The host ligands of PfEMP1 include CD36, ICAM-1 and the ABO antigens. By employing a series of population- and family-based association studies from multiple African populations, we examined whether variation in the genes underlying these molecules affects susceptibility to severe malaria. Our results suggest that a common frameshift mutation in the ABO glycosyltransferase, responsible for blood group O, is associated with protection from severe malarial phenotypes (P=2x10⁻⁷), particularly severe malarial anaemia. However, we found no significant disease associations with variation in either the ICAM1 or CD36 genes. We focused on two particular functional polymorphisms, the missense ICAM-1Kilifi and the CD36 nonsense mutation T1264G. We genotyped both markers in around 10,000 individuals, but neither demonstrated an association with severe malarial phenotypes. Malaria has been a profound selection pressure shaping human genetic diversity. The last decade has seen the development of several haplotype-based methods to detect signatures of recent positive evolutionary selection. These techniques are potentially invaluable tools in our hunt for genetic variants that protect from life threatening malaria. We used simulations and empirical data from the International HapMap Project to demonstrate the validity of searching for long regions of haplotype homozygosity, as an approach to finding alleles undergoing selective sweeps. We analysed genetic data from a range of populations, particularly those utilized by HapMap, to investigate whether our candidate genes were associated with signals of recent positive selection. We characterized the distribution of a selection event associated with the CD36 1264G allele, focused in Central-West Africa, and demonstrated a novel signal of low population differentiation at the ABO gene, suggestive of longstanding balancing selection. Our work confirms that variation in the host ligands of PfEMP1 modulates severe malaria susceptibility, and highlights the value of using signals of selection, along with functional experiments and genetic association studies, to dissect the biology of severe malaria.
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Galagedara, Nelomie Nayanathara. "Identification of Quantitative Trait Loci for Resistance to Tan Spot in Durum Wheat." Thesis, North Dakota State University, 2018. https://hdl.handle.net/10365/28765.
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Tan spot, caused by Pyrenophora tritici-repentis (Ptr), is a major foliar disease on wheat. The pathosystem involves three pairs of necrotrophic effector (NE) and host sensitivity (S) gene interactions, namely Ptr ToxA-Tsn1, Ptr ToxB-Tsc2 and Ptr ToxC-Tsc1. Additionally, genetic factors conferring race-nonspecific resistance have been identified. The objectives of this study were to map tan spot resistance QTL and investigate the role of NE-S interactions in disease in durum using association and bi-parental mapping. Evaluation of a worldwide collection of durum accessions allowed identifying highly resistant nineteen lines to multiple Ptr races. Association mapping revealed genomic regions on chromosomes 1A, 2B and 3B significantly associated with resistance to tan spot, which likely correspond to Tsc1, Tsc2 and racenonspecific resistance. Using a bi-parental population derived from Ben and PI 41025, we found that ToxA-Tsn1 interaction plays no significant role in disease, instead a major race-nonspecific QTL on chromosome 5A was identified.
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Aryamanesh, Nader. "Chickpea improvement through genetic analysis and quantitative trait locus (QTL) mapping of ascochyta blight resistence using wild Cicer species." University of Western Australia. School of Plant Biology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0072.
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[Truncated abstract] The genetics of ascochyta blight resistance was studied in five 5 x 5 half-diallel cross sets involving seven genotypes of chickpea (ICC 3996, Almaz, Lasseter, Kaniva, 24B-Isoline, IG 9337 and Kimberley Large), three accessions of Cicer reticulatum (ILWC 118, ILWC 139 and ILWC 184) and one accession of C. echinospermum (ILWC 181) under field conditions. Both F1 and F2 generations were used in the diallel analysis. Almaz, ICC 3996 and ILWC 118 were the most resistant genotypes. Estimates of genetic parameters, following Hayman's method, showed significant additive and dominant gene actions. The analysis also revealed the involvement of both major and minor genes. Susceptibility was dominant over resistance to ascochyta blight. The recessive alleles were concentrated in the two resistant chickpea parents ICC 3996 and Almaz, and one C. reticulatum genotype ILWC 118. High narrow-sense heritability (ranging from 82 to 86% for F1 generations, and 43 to 63% for F2 generations) indicates that additive gene effects were more important than non-additive gene effects in the inheritance of the trait and greater genetic gain by breeding resistant chickpea cultivars using carefully selected parental genotypes. Current simple leaf varieties are often susceptible to ascochyta blight disease whereas varieties of other leaf types range from resistant to susceptible. The inheritance of ascochyta blight resistance and different leaf types and their correlation were investigated in intraspecific progeny derived from crosses among two resistant genotypes with normal leaf type (ICC 3996 and Almaz), one susceptible simple leaf type (Kimberley Large) and one susceptible multipinnate leaf type (24 B-Isoline). ... An interspecific F2 mapping population derived from a cross between chickpea accession ICC 3996 (resistant to ascochyta blight, early flowering, and semi-erect plant growth habit) and C. reticulatum accession ILWC 184 (susceptible to ascochyta blight, ii late flowering, and prostrate plant growth habit) was used for constructing a genetic linkage map. F2 plants were cloned through stem cuttings taken at pre-flowering stage, treated with plant growth regulator powder (0.5 mg/g indole butyric acid (IBA) and 0.5 mg/g naphthalene acetic acid (NAA)) and grown in a sand + potting mix substrate. Clones were screened for ascochyta blight resistance in controlled environment conditions using a 19 scale. Three quantitative trait loci (QTLs) were found for ascochyta blight resistance in this population. Two linked QTLs, located on linkage group (LG) 4, explained 21.1% and 4.9% of the phenotypic variation. The other QTL, located on LG3, explained 22.7% of the phenotypic variation for ascochyta blight resistance. These QTLs explained almost 49% of the variation for ascochyta blight resistance. LG3 had two major QTLs for days to flowering (explaining 90.2% of phenotypic variation) and a major single QTL for plant growth habit (explaining 95.2% of phenotypic variation). There was a negative correlation between ascochyta blight resistance and days to flowering, and a positive correlation between days to flowering and plant growth habit. The flanking markers for ascochyta blight resistance or other morphological characters can be used in marker-assisted selections to facilitate breeding programs.
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Melville, Scott Andrew Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Disease gene mapping in border collie dogs." Awarded by:University of New South Wales. School of Biotechnology and Biomolecular Sciences, 2006. http://handle.unsw.edu.au/1959.4/25511.
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Pedigree dog breeds are genetically isolated and inbred populations with characteristics specific to each breed. Some breeds carry genetic diseases which affect the health of the animals, but may also serve as a valuable model to identify genes involved in human disease. In the Border Collie breed in Australia, the identification of two disease genes would enable breeders to DNA test their animals and prevent future cases. Over 530 samples were collected to identify the genes responsible for these diseases through linkage mapping and candidate gene approaches. Collie Eye Anomaly (CEA) defines a group of symptoms that cause the incorrect development of different regions within the eye, and may also result in the detachment of the retina. The presence of the disease in different breeds of collies suggests that the disease originated before the differentiation of the collie breeds. The CEA gene was mapped to a region of CFA37, but the disease gene was identified by another research group. Neuronal Ceroid Lipofuscinosis (NCL) is a fatal neurodegenerative disorder that affects Border Collie dogs from approximately 16 months of age. The disease is inherited in an autosomal recessive manner and affected animals display a range of physiological and behavioural symptoms that include loss of muscular control, nervousness and sometimes aggression. Due to the debilitating nature of the disease, dogs rarely survive beyond 28 months of age. Microsatellite markers were used to exclude the Border Collie NCL gene from the region of the English Setter NCL gene (homolog of human NCL gene CLN8). Further work mapped the disease gene to CFA22, in a region containing the homolog for CLN5, one of the identified human disease genes for NCL. Subsequent sequencing of canine CLN5 revealed a nonsense mutation (c.619C>T, Q206X) that co-segregated with NCL in Border Collie pedigrees. This truncation mutation resulted in a protein product of similar size to some mutations identified in human CLN5 and therefore the Border Collie may make a good model for future NCL studies. With DNA testing now available, breeders of Border Collies can now ensure that no animal will die of NCL.
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Fernandez, Pedro. "A candidate and novel gene search to identify the PFHBII-causative gene." Thesis, Stellenbosch : Stellenbosch University, 2004. http://hdl.handle.net/10019.1/36913.
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Thesis (PhD)--Stellenbosch University, 2004.Bibliography
ENGLISH ABSTRACT: Heart failure due to cardiomyopathy or cardiac conduction disease is a major cause of mortality and morbidity in both developed and developing countries. Although defined as separate clinical entities, inherited forms of cardiomyopathies and cardiac conduction disorders have been identified that present with overlapping clinical features and/or have common molecular aetiologies. The objective of the present study was to identify the molecular cause of progressive familial heart block type II (PFHBII), an inherited cardiac conduction disorder that segregates in a South African Caucasian Afrikaner family (Brink and Torrington, 1977). The availability of family data tracing the segregation of PFHBII meant that linkage analysis could be employed to identify the chromosomal location of the disease-causative gene. Human Genome Project (HGP) databases have provided additional resources to facilitate the identification of positional candidate genes. Clinical examinations were performed on individuals of the PFHBII-affected family, and, where available, clinical records of subjects examined in a previous study by Brink and Torrington (1977) were re-assessed. Retrospective data suggested redefining the classification of PFHBII. Subsequently, linkage analysis was used to test described dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and cardiac conduction-causative loci on chromosomes 1, 2, 3, 6, 7, 9, 11, 14, 15 and 19 for their involvement in the development of PFHBII. Once a locus was mapped, bioinformatics tools were applied to identify and prioritise positional candidate genes for mutation screening. The retrospective and prospective clinical study redefined PFHBII as a cardiac conduction and DCM-associated disorder and simultaneously allowed more family members to be traced. Fortuitously, candidate loci linkage analysis mapped the PFHBII locus to chromosome 1q32, to a region that overlapped a previously described DCM-associated disorder (CMD1D), by the generation of a maximum pairwise lod score of 3.13 at D1S3753 (theta [θ]=0.0) and a maximum multipoint lod score of 3.7 between D1S3753 and D1S414. However, genetic fine mapping and haplotype analysis placed the PFHBII-causative locus distal to the CMD1D locus, within a 3.9 centimorgan (cM) interval on chromosome 1q32.2-q32.3, telomeric of D1S70 and centromeric of D1S505. Bioinformatics analyses prioritised seven candidate genes for mutation analysis, namely, a gene encoding a potassium channel (KCNH1), an extracellular matrix protein (LAMB3), a protein phosphatase (PPP2R5A), an adapter protein that interacts with a cytoskeletal protein (T3JAM), a putative acyltransferase (KIAA0205) and two genes encoding proteins possibly involved in energy homeostasis (RAMP and VWS59). The PFHBII-causative mutation was not identified, although single sequence variations were identified in four of the seven candidate genes that were screened. Although the molecular aetiology was not established, the present study defined the underlying involvement of DCM in the pathogenesis of PFHBII. The new clinical classification of PFHBII has been published (Fernandez et al., 2004) and should lead to tracing more affected individuals in South Africa or elsewhere. The identification of a novel disease-causative locus may point toward the future identification of a new DCM-associated aetiology, which, in turn, might provide insights towards understanding the associated molecular pathophysiologies of heart failure.
AFRIKAANSE OPSOMMING: Hartversaking as gevolg van kardiomiopatie of kardiale geleidingsiekte is ‘n hoof-oorsaak van mortaliteit and morbiditeit in beide ontwikkelde en ontwikkelende lande. Alhoewel gedefinieer as verskillende kliniese entiteite is oorerflike vorms van kardiomiopatie en kardiale geleidingsstoornisse geïdentifiseer met oorvleuelende kliniese eienskappe en/of molukulêre oorsake. Die doelwit van hierdie studie was om die molukulêre oorsaak van progressiewe familiële hartblok tipe II (PFHBII), ‘n oorerflike kardiale geleidingsstoornis, wat in ‘n Suid-Afrikaanse Kaukasiër familie segregeer (Brink en Torrington, 1977), te identifiseer. Die beskikbaarheid van familie data, beteken dat koppelingsanalise gebruik kan word om die chromosomale posisie van die siekte-veroorsakende geen te identifiseer. Menslike Genoom Projek (MGP) databanke het addisionele hulpbronne beskikbaar gestel om die identifikasie van posisionele kandidaat gene te vergemaklik. Kliniese ondersoeke is uitgevoer op PFHBII-geaffekteerde familielede, en waar beskikbaar is kliniese rekords van persone, wat in ‘n vorige studie deur Brink en Torrington (1977) geassesseer was, herontleed. Retrospektiewe data-analise het die kliniese herdefinisie van PFHBII voorgestel. Daarna is koppelingsanalise gebruik om dilateerde kardiomiopatie (DKM), hipertrofiese kardiomiopatie (HKM) en kardiale geleidingssiekte-veroorsakende loki op chromosoom 1, 2, 3, 6, 7, 9, 11, 14, 15 en 19 te ondersoek vir hul moontlike bydrae tot die ontwikkeling van PFHBII. Toe die lokus gekarteer was, is bioinformatiese ondersoeke gebruik om posisionele kandidaat gene te identifiseer en prioritiseer vir mutasie analise. Die retrospektiewe en prospektiewe kliniese ondersoek het PFHBII herdefinieer as ‘n geleidingsstoornis en DKM-verbonde siekte, en terselfde tyd het dit gelei tot die opsporing van nog familielede. Toevallig het kandidaat loki-analise die PFHBII lokus op chromosoom 1q32 gekarteer, na ‘n gebied wat met ‘n voorheen-beskyfde DKM-verbonde stoornis (CMD1D) oorvleuel, met die opwekking van ‘n makisimum paargewyse lod-getal van 3.13 by D1S3753 (theta [θ] = 0.0) en ‘n maksimum multipunt lod-getal van 3.7 tussen D1S3753 en D1S414. Genetiese fynkartering en haplotipe-analise het die PFHBII-veroorsakende lokus afwaards van die CMD1D lokus geplaas, in ‘n 3.9 centimorgan (cM) gebied op chromosoom 1q32.2-q32.3, telomeries van D1S70 en sentromeries van D1S505. Bioinformatiese analise het daarnatoe gelei dat sewe kandidaat gene vir mutasie analise geprioritiseerd is, naamlik, gene wat onderskeidelik ‘n kalium kanaal (KCNH1), ‘n ekstrasellulêre matriksproteïen (LAMB3), ‘n proteïen fosfatase (PPP2R5A), ‘n aansluiter proteïen wat met ‘n sitoskilet proteïen bind (T3JAM), ‘n asieltansferase (KIAA0205) en twee gene moontlik betrokke in energie homeostase (RAMP en VWS59) enkodeer. Die PFHBII-veroorsakende geen is nie geïdentifiseer nie, alhoewel enkele volgorde-wisselings geïdentifiseer is in vier van die sewe geanaliseerde kandidaat gene. Alhowel die molekulêre oorsaak van die siekte nie vasgestel is nie, het die huidige studie die onderliggende betrokkenheid van DKM in die pathogenese van PFHBII gedefinieer. Die nuwe kliniese klassifikasie van PFHBII is gepubiliseer (Fernandez et al., 2004) en sal lei tot die identifisering van nog geaffekteerde persone in Suid Afrika of in ander lande. Die identifikasie van ‘n nuwe siekte-verbonde lokus mag lei tot die toekomstige identifikasie van ‘n nuwe DKM-verbonde genetiese oorsaak wat, opsig self, dalk insig kan gee in die molekulêre patofisiologie van hartversaking.
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Moody, Adrian John. "Mapping genetic resistance to infectious bursal disease." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326754.
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Good, David Andrew, and n/a. "Genetic Loci for Paget's Disease of Bone." Griffith University. School of Biomolecular and Biomedical Science, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040319.125358.
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Paget's disease of the bone is a skeletal disorder of unknown cause. This disease is characterised by excessive and abnormal bone remodelling brought about by increased bone resorption followed by disorganised bone formation. Increased bone turnover results in a disorganised mosaic of woven and lamellar bone at affected skeletal sites. This produces bone that is expanded in size, less compact, more vascular, and more susceptible to deformity or fracture than normal bone. Symptoms of Paget's disease may include bone pain, bone deformity, excessive warmth over bone from hypervascularity, secondary arthritis, and a variety of neurologic complications caused in most instances by compression of the neural tissues adjacent to pagetic bone. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. The identification of the molecular basis of Paget's disease is fundamental for an understanding of the cause of the disease, for identifying subjects at risk at a preclinical stage, and for the development of more effective preventive and therapeutic strategies for the management of the condition. With this in mind, the aim of this project is to identify genetic loci, in a large pedigree, that may harbour genes responsible for Paget's disease of bone. A large Australian family with evidence of Paget's disease was recruited for these studies (Chapter 3). This pedigree has characterised over 250 individuals, with 49 informative individuals affected with Paget's disease of bone, 31 of whom are available for genotypic analysis. The pattern of disease in these individuals is polystotic, with sites of involvement including the spine, pelvis, skull and femur. Although the affected individuals have a severe early-onset form of the disease, the clinical features of the pedigree suggest that the affected family members have Paget's disease and not familial expansile osteolysis (a disease with some similarities to Paget's disease), as our patients have extensive skull and axial skeletal involvement. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Due to the large size of this family and multiple affected members, this pedigree is a unique resource for the detection of the susceptibility gene in Paget's disease. The first susceptibility loci for Paget's disease of bone have been mapped by other investigators to chromosome 6p21 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees. Linkage analysis of the Australian pedigree in these studies was performed with markers at PDB1: these data showed significant exclusion of linkage, with LOD scores < - 2 in this region (Chapter 4). Linkage analysis of microsatellite markers from the PDB2 region excluded linkage with this region also, with a 30 cM exclusion region (LOD score < -2.0) centred on D18S42 (Chapter 4). This locus on chromosome 18q21.1-q22 contains a serine protease (serpin) cluster with similarities to chromosome 6p21. Linkage analysis of this region also failed to provide evidence of linkage to this locus (Chapter 4). These data are consistent with genetic heterogeneity of Paget's disease of bone. A gene essential for osteoclast formation encoding receptor activator of nuclear factor-kB (RANK), TNFRSF11A, has been previously mapped to the PDB2 region. Mutations in the TNFRSF11A gene have been identified segregating in pedigrees with Familial Expansile Osteolysis and early onset familial Paget's disease, however, linkage studies and mutation screening have excluded the involvement of RANK in the majority of Paget's disease patients. For the Australian pedigree, mutation screening at the TNFRSF11A locus revealed no mutations segregating with affected individuals with Paget's disease (Chapter 4). Based on these findings, our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree; this gene should be identifiable using a microsatellite genome-wide scan followed by positional cloning. A genome-wide scan of the Australian pedigree was carried out, followed by fine mapping and multipoint analysis in regions of interest (Chapter 5). The peak 2-point LOD scores from the genome-wide scan were LOD = 2.75 at D7S507 and LOD = 1.76 at D18S70. Two additional regions were also considered for fine mapping: chromosome 19p11-q13.1 with a LOD of 1.58 and chromosome 5q35-qter with a LOD of 1.57. Multipoint and haplotype analysis of markers flanking D7S507 did not support linkage to this region (Chapter 5). Similarly, fine mapping of chromosome 19p11-q13.1 failed to support linkage to this region (Chapter 5). Linkage analysis with additional markers in the region on chromosome 5q35-qter revealed a peak multipoint LOD score of 6.77 (Chapter 5). A distinct haplotype was shown to segregate with all members of the family, except the offspring of III-5 and III-6. Haplotype analysis of markers flanking D18S70 demonstrated a haplotype segregating with Paget's disease in a large sub-pedigree (descendants of III-3 and III-4) (Chapter 5). This sub-pedigree had a significantly lower age at diagnosis than the rest of the pedigree (51.2 + 8.5 vs. 64.2 + 9.7 years, p = 0.0012). Linkage analysis of this sub-pedigree demonstrated a peak two-point LOD score of 4.23 at marker D18S1390 (q = 0.00), and a peak multipoint LOD score of 4.71, at marker D18S70. An implication of these data is that 18q23 harbours a novel modifier gene for reducing the age of onset of Paget's disease of bone. A number of candidate Paget's genes have previously been identified on chromosome 18q23, including the nuclear factor of activated T cells (NFATc1), membrane-associated guanylated kinase (MAGUK) and a zinc finger protein. Candidate gene sequencing of these genes in these studies has failed to identify mutations segregating with affected family members in the sub-pedigree linked to chromosome 18q23 (Chapter 6). More recently, a mutation in the gene encoding the ubiquitin-binding protein sequestosome 1 (SQSTM/p62) has been shown to segregate with affected members of Paget's disease families of French-Canadian origin. In this study, a single base pair deletion (1215delC) was identified as segregating with the majority of affected members in the pedigree (Chapter 6). This deletion introduces a stop codon at amino acid position 392 which potentially results in early termination of the protein and loss of the ubiquitin binding domain. The three affected members of the family that do not share the affected haplotype do not carry a mutation in the coding region of SQSTM/p62. Screening of affected members from 10 further Paget's disease families identified the previously reported P392L mutation in 2 (20%) families. No SQSTM1/p62 coding mutations have been found in the remaining 8 families or in 113 aged matched controls. In conclusion, this project has identified genetic loci and mutations that segregate with individuals affected with Paget's disease. Further investigation of the functional significance of the genetic changes at these loci is expected to lead to a better understanding of the molecular basis of this disease.
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Magnusson, Veronica. "Genetic studies on Systemic Lupus Erythematosus : A fine mapping and candidate gene approach." Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2869.
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Linkage in the 2q37 region was evaluated using microsatellite markers in multi-case families from Sweden, Iceland and Norway. Both the two-point and the multipoint linkage analysis show highly significant LOD scores (Z=4.51 and 6.03, respectively). Linkage disequilibrium mapping indicates that some association exists in this region. The PDCD1 gene was suggested as a candidate gene within the 2q37 locus due to its importance in immune regulation. Indeed, one haplotype, described by the presence of allele A of the PD1.3 SNP located within intron 4 of this gene, shows linkage to SLE in the Nordic families. The PD1.3A allele is also found to be strongly associated in familiar and sporadic cases of SLE in Europeans and Mexicans. Functional studies further support PD1.3A to be a susceptibility allele for SLE.
The 1q23 region, containing the genes for the low affinity Fcγ receptors, was fine mapped using single- and multi- case families of various origins. Genetic variants of those genes were analysed and association is found to both the risk alleles of FcγRIIA and FcγRIIIA in all families. In these families, a single haplotype carrying both risk alleles is predominantly transmitted to patients with SLE, suggesting a presence of linkage disequilibrium between those two genes. FcγRIIA and FcγRIIIA are also found to be associated to SLE and lupus nephritis in a case-control cohort from Sweden. In the same cohort, the PD1.3A allele shows strong association to lupus nephritis. We suggest that there may be an additive effect between FcγRIIA and PDCD1, since having the disease-associated genotypes at both loci gives an increased risk for developing lupus nephritis.
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disorder with a complex multifactorial aetiology. Genetic studies suggest that several genes are involved in disease pathogenesis and that extended genetic heterogeneity is present.
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Skipper, Lisa Marie. "Parkinson's disease susceptibility : genetic mapping in an isolated population." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446678/.
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Parkinson's disease (PD) is an aetiologically complex, progressive and debilitating neurodegenerative disorder that primarily affects the elderly population. It is characterised clinically by the presence of motor symptoms including resting tremor, bradykinesia and rigidity; pathologically by neuronal loss within mid brain regions and intraneuronal inclusions comprising numerous protein aggregates. Disease risk factors are both environmental and genetic. To date, at least 10 genetic loci are implicated and specific mutations have been identified in SNCA, PRKN, UCH-Ll, DJ-1 and PINKL Variability within the MAPT gene has also been associated with disease risk. Population isolates are a powerful tool for the dissection of genetically complex disorders, due to expected genetic homogeneity and linkage disequilibrium (LD) levels. This project has focused upon a population isolate from Trondheim, central Norway, in which most individuals with PD show no family history of disease. In the first study of the genetic factors involved in PD within the Norwegian population, we chose to investigate recessive (PARK2, PARK6 and PARK7) and susceptibility (MAPT and PARK 10) loci, which may manifest as sporadic disease. Analysis of PRKN (PARK2) suggested that this locus contributes to PD in the Norwegian population and that the high frequency of the A82E mutation in the Trondheim community is due to a founder effect. In addition, a novel proline insertion mutation was identified. Detailed examination of the MAPT H1 haplotype associated with parkinsonism, showed that 'H1' consists of a group of related but distinct haplotypes, one of which is preferentially associated with PD. The variability most associated with disease was shown to lie at the 5' end of MAPT, encompassing exons 1 to 4. Candidate gene analysis and novel multipoint LD mapping methods at PARK10 identified two genes, EPS15 and NRDl, which may also contribute to PD risk. Further molecular genetic analysis will contribute to the understanding of pathogenic mechanisms through the use of cellular and animal models, and ultimately the development of both palliative and preventative therapies.
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Groenewald, Johannes Zacharias. "Tagging and mapping of prominent structural genes on chromosome arm 7DL of common wheat." Thesis, Stellenbosch : Stellenbosch University, 2001. http://hdl.handle.net/10019.1/52474.
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Thesis (PhD (Agric)) -- Stellenbosch University, 2001.ENGLISH ABSTRACT: Chromosome arm 7DL of common wheat carries genes for agronomically important traits such as leaf rust, stem rust, Russian wheat aphid and eye spot resistance. Some of these genes occur on introgressed foreign chromatin, which restricts their utility in breeding. The 7DL genetic maps are poorly resolved, which seriously hampers attempts to manipulate the genes and introgressed regions in breeding. This dissertation represents an attempt to improve our knowledge of the relative map positions of three resistance genes that have significant potential for use in local breeding programmes. The leaf rust resistance gene, Lr19, is located on a Thinopyrum ponticum-derived translocation which occupies a large part of the terminal end of 7DL. The translocation also carries genes for less favourable traits such as yellow flour colour. Attempts have been made to reduce the size of the translocation through allosyndetic pairing induction; the primary aims being to remove deleterious genes and to minimise the amount of foreign chromatin associated with Lr19 so it can be recombined with other useful 7DL genes. Twenty-nine 'Indis'-derived Lr 19 deletion mutants were previously produced by gamma irradiation and a physical map was constructed. In this study, the set of mutant lines were further analysed using 144 Sse8387I/Msei and 32 EcoRI/Msel amplified fragment length polymorphism (AFLP) primer combinations. The previous physical map, which was based on five restriction fragment length polymorphism (RFLP) markers and five structural gene loci, was extended and now includes 95 novel AFLP markers (86 Sse8387I/Msei and 9EcoRI!Msel markers), of which seven map close to Lr 19. Most of the deletions could be ordered according to size and the improved map has already been used to characterise shortened recombinant forms of the Lr 19 translocation. An unsuccessful attempt was made to convert one of the seven markers closest to Lr 19 into a sequence-specific marker. However, an AFLP marker located distally from Lr 19 was successfully converted into a sequence-specific marker in collaboration with other researchers. An attempt was also made to map and tag the Russian wheat aphid (RWA) resistance gene, Dn5. A doubled haploid mapping population consisting of 94 lines was created and typed for Dn5, four microsatellite loci and the endopeptidase locus, Ep-Dl. The Dn5 locus mapped 25.4 cM and 28.6 cM distally from Xg.vm111 and Xg.vm437, respectively, but was not linked to Xgwm428, Xgwm3 7 or Ep-Dl. Tagging of Dn5 was attempted by screening twelve homozygous resistant and seven homozygous susceptible F2 lines from a cross between 'Chinese Spring' and 'PI 294994' with 70 Sse8387IIi\1sei AFLP primer combinations. Only two potentially useful polymorphisms (one in coupling and one in repulsion phase) were identified. Conversion of the coupling phase marker to a sequence-specific marker was not successful. The eyespot resistance gene, Pchl , was derived from Triticum ventricosum and is present in the wheat VPM-1. Close association between Pchl and the endopeptidase Ep-Dlb allele has been reported previously. Pchl/Ep-Dl was tagged by screening ten wheat genotypes (each homozygous for the confirmed presence or absence of Pchl and/or Ep-Dl b) with 36 Sse83 87I/ Msei AFLP primer combinations. Three AFLP markers were closely associated with Pchl I Ep-D 1, one of which was targeted for conversion into a sequence-specific marker. The sequence-specific marker contained a microsatellite core motif and was found to be useful for tagging Pchl!Ep-Dl. A genetic distance of 2 cM was calculated between the novel microsatellite marker and Ep-Dl. The microsatellite marker was also polymorphic for the Lr 19 translocation and it was possible to map it between the Wsp-Dl and Sr25 loci. In this dissertation, mapping and/or tagging of three important resistance genes were achieved. Due to the fact that all markers used in these studies were not polymorphic between all of the targeted regions, it was not possible to fully integrate the data obtained for the three regions.
AFRIKAANSE OPSOMMING: Chromosoom arm 7DL van broodkoring dra gene vir agronomies-belangrike kenrnerke soos blaarroes, stamroes, Russiese koringluis en oogvlek weerstand. Sommige van hierdie gene kom voor in blokke spesie-verhaalde chromatien wat hul bruikbaarheid in teling beperk. Die genetiese kaarte van 7DL is swak ontwikkel en dit maak dit baie moeilik om hierdie gene en spesie-verhaalde streke tydens teling te manipuleer. Hierdie proefskrif verteenwoordig 'n paging om kennis van die relatiewe kaart liggings van drie weerstandsgene, met betekenisvolle potensiaal in plaaslike tee! programme, te verbreed. Die blaarroes weerstandsgeen, Lr 19, kom voor op 'n Thinopyrum ponticum-verhaalde translokasie wat 'n groot terminale gedeelte van 7DL beslaan. Die translokasie dra ook gene vir minder gewensde kenrnerke soos gee! meelkleur. Pogings is aangewend om die translokasie deur homoeoloe parings-induksie te verkort. Die doe! was om nadelige gene te verplaas en die hoeveelheid vreemde chromatien geassosieer met Lr 19 te minimiseer sodat dit met ander nuttige gene op 7DL gerekombineer kan word. Nege-en-twintig 'Indis'-verhaalde Lr 19 delesie mutante is vroeer met gamma bestraling geproduseer en gebruik om 'n fisiese kaart op te stel. Teenswoordig is die stel mutante verder ontleed met behulp van 144 Sse8387I!Msei en 32 EcoRII Msel amplifikasie-fragment-lengte-polimorfisme (AFLP) inleier kombinasies. Die bestaande fisiese kaart, wat gebaseer was op vyf restriksie-fragment-lengte-polimorfisme (RFLP) merkers en vyf strukturele geen loki, is uitgebrei en sluit nou 95 unieke AFLP merkers (86 Sse8387I/Msel en 9EcoRI/Msel merkers) in, waarvan sewe naby aan Lr19 karteer. Die meeste van die delesies kon op grond van hulle grootte gegroepeer word en die verbeterde fisiese kaart is alreeds gebruik om verkorte rekombinante vorms van die Lr 19 translokasie te karakteriseer. 'n Onsuksesvolle paging is aangewend om een van die sewe merkers naaste aan Lr 19 om te skakel na 'n volgorde-spesifieke merker. 'n AFLP merker wat distaal van Lr 19 karteer is egter wel suksesvol in samewerking met ander navorsers omgeskakel na 'n volgordespesifieke merker. 'n Paging is ook aangewend om die Russiese koringluis (RKL) weerstandsgeen, Dn5, te karteer en merkers gekoppel aan die geen te identifiseer. 'n Verdubbelde-haplo!ede karteringspopulasie van 94 lyne is geskep en getipeer vir Dn5, vier mikrosatelliet loki en die endopeptidase lokus, Ep-D1. Die Dn5 lokus karteer 25.4 cM en 28.6 cM distaal van Xgwml11 en Xgwm437, respektiewelik, maar was me gekoppel met Xgwm428, Xgwm37 of Ep-D1 me. Twaalf homosigoties weerstandbiedende en sewe homosigoties vatbare F2 lyne uit die kruising: 'Chinese Spring' I 'PI 294994' is met 70 Sse8387VMsel AFLP inleier kombinasies getoets in 'n poging om merkers vir Dn5 te identifiseer. Slegs twee moontlik bruikbare polimorfismes (een in koppelings- en een in repulsie fase ), is ge'identifiseer. Omskakeling van die koppelingsfase merker na 'n volgorde-spesifieke merker was onsuksesvol. Die oogvlek weerstandsgeen, Pch1, is uit Triticum ventricosum oorgedra en kom voor in die koringlyn, VPM-1. Noue koppeling van Pch1 en die endopeptidase alleel, Ep-D1 b, is vantevore gerapporteer. Merkers is vir P chl I Ep-D 1 gevind deur tien koring genoti pes ( elkeen homosigoties vir die bevestigde teenwoordigheid of afwesigheid van Pch1 en/of Ep-D1 b) te toets met 36 Sse83871/kfsel AFLP inleier kombinasies. Drie AFLP merkers is gevind wat nou koppel met Pchl!Ep-D1 , waarvan een gekies is vir omskakeling na 'n volgorde-spesifieke merker. Die volgorde-spesifieke merker het 'n mikrosatelliet kernmotief bevat en was nuttig as merker vir Pch1/Ep-D1. 'n Genetiese afstand van 2 cM is tussen die unieke mikrosatelliet merker en Ep-D1 bereken. Die mikrosatelliet merker was ook polimorfies vir die Lr 19 translokasie en dit is tussen die Wsp-D1 en Sr25 loki gekarteer. Kartering en/of identifikasie van merkers vir drie belangrike weerstandsgene was suksesvol in hierdie studie. Omdat al die merkers wat gebruik is, nie polimorf was tussen al die streke van belang nie, was dit nie moontlik om die data vir elk van die drie streke ten volle te integreer nie.
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Nordquist, Niklas. "Genetic Studies of Rheumatoid Arthritis using Animal Models." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5117-9/.
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Johanneson, Bo. "Genetic Mapping of Susceptibility Genes for Systemic Lupus Erythematosus." Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2950.
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Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unknown etiology. The aim of this thesis was to identify susceptibility regions through genetic mapping, using model-based linkage analysis on nuclear and extended SLE multicase families.
In the first paper we performed a genome scan on 19 genetically homogenous Icelandic and Swedish families. One region at 2q37 was identified with a significant linkage with contribution from both populations (Z=4.24). Five other regions 2q11, 4p13, 9p22, 9p13 and 9q13 showed suggestive linkage (Z>2.0).
In the second paper, 87 families from 10 different countries were analysed only for chromosome 1. One region at 1q31 showed significant linkage (Z=3.79) with contribution from families from all populations, including Mexicans and Europeans. Four other regions 1p36, 1p21, 1q23, and 1q25, showed levels of suggestive linkage. Linkage for most regions was highly dependent on what population was used, which indicated strong genetic heterogeneity in the genetic susceptibility for SLE.
In the two last papers, we used the positional candidate gene strategy, in order to investigate candidate genes in two regions linked to SLE. For the Bcl-2 gene (at 18q21) we could not detect any association with SLE using three different markers. However, when we investigated the tightly linked low-affinity family of FcγR genes (at 1q23), we could find association for two risk alleles in the FcγRIIA and FcγRIIIA genes. The risk alleles were transmitted to SLE patients on one specific haplotype and therefore are not independent risk alleles.
The results show that model-based linkage analysis is a strong approach in the search for susceptibility genes behind complex diseases like SLE.
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Craig, Nicola Jane. "Genetic and physical mapping of the rat agu locus." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341722.
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Heyns, I. C. "Mapping and restructuring of an Ae. kotschyi derived translocation segment in common wheat." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/5172.
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Thesis (PhD (Genetics))--University of Stellenbosch, 2010.Includes bibliography.
ENGLISH ABSTRACT: The wild relatives are an important source of new genes for the genetic improvement of wheat. At Stellenbosch University the leaf and stripe rust resistance genes Lr54 and Yr37 were transferred from Aegilops kotschyi to chromosome 2DL of wheat. In an attempt to reduce the size of the whole-arm translocation on which the resistance genes occur, homoeologous pairing was induced between the wheat and corresponding Ae. kotschyi chromatin. The purpose of this study was to: (i) Evaluate the testcross progeny thus obtained; identify translocation recombinants that retained Lr54/Yr37 and to characterize these using molecular markers (ii) Test for the presence of genes for photoperiod insensitivity (Ppd) and reduced height (Rht) believed to be associated with the translocation (iii) Develop a SCAR marker for the most useful recombinant that could be recovered. Ten putative translocation recombinants were identified following the screening of 159 hemizygous testcross F1 plants with three microsatellite markers specific for chromosome arm 2DL. The recombinants were then characterized with another five microsatellite markers. Using the eight microsatellite markers the recombinants were ordered in two size categories with recombinant #74 being the shortest and having retained only proximal alien chromatin on 2DL. In addition to microsatellite markers, RAPDs, RGAs, AFLPs and SCAR markers were genetically mapped to the translocation and further resolved the recombinants into three size categories. In an attempt to find suitable markers linked to the shortest recombinant (#74) a polymorphic 410 bp AFLP fragment produced with the enzyme/selective nucleotide combination EcoRI – AAC/MseI – CAT, was converted into a dominant SCAR marker. In addition three microsatellite markers that mapped to recombinant #74 provided a useful recessive molecular marker system to detect Lr54/Yr37. Evaluation of the 10 recombinants with four 2DS-specific microsatellite markers revealed a large deletion of this chromosome arm in recombinant #74. This deletion may affect plant phenotypic characteristics and a strategy to replace the deleted region in recombinant #74 is proposed. To test for the presence of a gene for photoperiod insensitivity on the translocation, translocation-carriers plus controls were subjected to long and short day treatments, and the effect on time to flowering was studied. However, no evidence was found for the presence of such a gene. A height experiment to test for the presence of an Rht gene on the translocation confirmed its presence. This gene (designated H) appeared to be different from Rht8 on chromosome 2DS and was mapped on 2DL. While H does not occur in a chromosome region that corresponds with the location of Rht8, it does not rule out the possibility that they could be orthologous loci. Plant height data obtained for recombinant #74 suggested that H was lost through recombination in this particular recombinant. A greenhouse experiment suggested that the full-length translocation increased 100 kernel mass but had a detrimental effect on overall plant yield. Since a much shorter recombinant (#74) has been obtained, this will also have to be evaluated for associated effects. Such an evaluation needs to be done under commercial growing conditions and should involve the comparison of near-isogenic bulks with and without recombinant chromosome #74. The stripe rust resistance gene (Yr37) was mapped by screening hemizygous TF2 progeny of the 10 recombinants with Puccinia striiformis pathotype 6E22A+. Recombinant #74 retained both Lr54 and Yr37 and the two genes therefore occur towards the centromere.
AFRIKAANSE OPSOMMING: Wilde verwante spesies is ‘n belangrike bron van nuwe gene vir die genetiese verbetering van koring. By die Universiteit van Stellenbosch is die blaar-roes en streep-roes weerstandsgene Lr54 en Yr37 vanaf Aegilops kotschyi na chromosoom 2DL van koring oorgedra. ‘n Poging is vervolgens aangewend om die vol-armtranslokasie waarop die weerstandsgene voorkom te verklein deur homoeoloë paring tussen die koring en ooreenstemmende Ae. kotschyi chromatien te induseer. Die doelstelling van hierdie studie was daarom as volg: (a) Evaluering van die verkreë toetskruis-nageslag asook die identifisering en karakterisering van translokasie rekombinante wat Lr54/Yr37 behou het. (b) Toetsing vir fotoperiode onsensitiwiteits- (Ppd) en verkorte plant-hoogte (Rht) gene wat moontlik op die translokasie kon voorkom. (c) Die ontwikkeling van ‘n volgorde-spesifieke polimerase kettingreaksie (PKR) vir die mees bruikbare rekombinant. Tien translokasie rekombinante is geïdentifiseer nadat 159 hemisigotiese toetskruis F1-plante met drie mikrosatelliet-merkers, spesifiek vir chromosoom-arm 2DL, ge-evalueer is. Die rekombinante is hierna met vyf verdere mikrosatellietmerkers getoets. Die data van die agt mikrosatelliet-loci het die rekombinante in twee grootte-kategorieë geplaas waarvan rekombinant #74 die kortste was met slegs die proksimale gedeelte van 2DL wat uit vreemde chromatien bestaan. Behalwe mikrosatellite-merkers is toevallig-geamplifiseerde polimorfiese DNS (RAPD), weerstandsgeen-analoog (RGA), geamplifiseerde volgordelengte polimorfisme (AFLP) en volgorde-gekarakteriseerde geamplifiseerde-streke (SCAR) merkers ook geneties op die translokasie gekarteer. Data van die addisionele merkers het dit moontlik gemaak om die rekombinante in drie grootte-kategorieë te skei. Pogings om ‘n merker vir die kortse rekombinant (#74) te vind, het gelei tot die omskakeling van ‘n 410 bp polimorfiese AFLP-fragment (geproduseer met die ensiem/selektiewenukleotied kombinasie EcoRI - AAC/MseI - CAT), na ‘n dominante, volgordespesifieke PKR-merker. Hierbenewens kan drie mikrosatelliet-merkers wat op rekombinant #74 karteer as resessiewe merkers vir die identifisering van Lr54/Yr37 gebruik word. Die evaluering van die 10 rekombinante met vier chromosoom 2DSspesifieke mikrosatelliet-merkers het ‘n groot delesie van chromosoom-arm 2DS in rekombinant #74 uitgewys. Die delesie mag plant fenotipiese kenmerke beïnvloed en daarom is ‘n strategie vir die vervanging daarvan in rekombinant #74 voorgestel. Ten einde te toets of ‘n geen vir fotoperiode-onsensitiwiteit op die translokaie voorkom is translokasie-draers en kontroles aan lang- en kortdag-behandelings onderwerp en is die effek hiervan op dae-tot-blom gemeet. Geen bewyse vir so ‘n geen kon gevind word nie. ‘n Hoogte-eksperiment om te toets vir die teenwoordigheid van ‘n Rht-geen op die translokasie, het bevestig dat so ‘n geen wel voorkom. Die geen (voorgestelde simbool H) is gekarteer op 2DL en verskil oënskynlik van Rht8 op chromosoom 2DS. Die verskillende chromosoom-ligging van H en Rht8 skakel egter nie die moontlikheid dat hulle ortoloë loci mag wees uit nie. Plant-hoogte data vir rekombinant #74 het daarop gedui dat H nie meer in hierdie rekombinant voorkom nie. Data van ‘n glashuis-eksperiment het daarop gedui dat die vollengte-translokasie 100-korrel-massa verhoog maar dat dit plant-opbrengs verlaag. Aangesien ‘n aansienlike korter rekombinant (#74) verkry is, sal dit ook vir gekoppelde effekte getoets moet word. So ‘n evaluering moet egter onder kommersiële toestande gedoen word met gebruik van naby isogeniese-lyne met en sonder rekombinante chromosoom #74. Die streep-roes weerstandgeen (Yr37) is gekarteer deur hemisigotiese TF2- nageslag van die 10 rekombinante te toets vir weerstand teen Puccinia striiformis patotipe 6E22A+. Rekombinant #74 het beide Lr54 en Yr37 behou en die twee gene karteer dus naby die sentromeer.
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Pound, Susan Elizabeth. "Genetic and physical mapping of autosomal dominant polycystic kidney disease." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/20118.
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A sample of 35 families with ADPKD from central Scotland, previously typed with two markers from the PKD1 region [3'HVR. However, there is one recombinant with CMM65 (D16S84), and one with 26-6 (D16S125), which localises PKD1 to between these markers. In order to obtain cloned DNA from this genetically defined region of interest, spanning approximately 750 kb of DNA, yeast artificial chromosomes (YACs) were isolated from available libraries.
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Maller, Julian Benjamin. "Fine scale mapping of genetic loci associated with human disease." Thesis, University of Oxford, 2013. https://ora.ox.ac.uk/objects/uuid:2e1dcc74-cccb-4253-961c-431e965bf204.
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Genome-wide association studies (GWAS) use custom SNP arrays that provide ef- fective genetic coverage, but do not detail the association of confirmed susceptibil- ity regions with as dense a marker map as possible. In this thesis I will describe a fine mapping study across 14 associated regions, in 8,000 samples from three dis- eases (Type 2 diabetes mellitus (T2D), coronary artery disease (CAD) and Graves Disease (GD)) and a control group, including over 5,500 successfully genotyped SNPs. We defined using Bayes theorem sets of SNPs (credible sets) that were 95% likely (posterior probability) to contain the causal disease variants. In three of the 14 regions TCF7L2 and CDKN2A/B in T2D and CTLA4 in GD, we found that much of the posterior probability after the fine mapping rested on a single SNP. In seven of the 14 regions (CDKN2A/B in CAD, CTLA4 in GD, and CDKAL1, FTO, HHEX, TCF7L2) and CDKN2A/B in T2D), including the three just mentioned, the credible sets are relatively small. For these regions, the fine mapping experi- ment has provided useful information, at least in excluding large numbers of SNPs from being causal. Almost none of the SNPs in our credible regions had obvious functions, illustrating our lack of knowledge of genome sequence in modulating gene expression and susceptibility to common disease. Based on this experiment, I outline and discuss the possibilities and challenges in identifying causal variants for complex traits through fine mapping of GWA signals. Further, I evaluate the possibility of using genotype imputation in the context of fine mapping, both as a method for fine mapping and as a way to increase efficiency in fine mapping studies.
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Heyns, I. C. "Mapping of chromosome arm 7DL of Triticum aestivum L." Thesis, Stellenbosch : University of Stellenbosch, 2005. http://hdl.handle.net/10019.1/1584.
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Thesis (MSc (Genetics))--University of Stellenbosch, 2005.The Russian wheat aphid, Diuraphis noxia (Mordvilko), is a serious insect pest of wheat and barley. It affects the quality and yield of grain by sucking plant sap from the newest growth whilst toxic substances are injected that destroy plant tissue. The Russian wheat aphid also acts as a vector of plant viruses. The cultivation of aphid resistant cultivars is the preferred control strategy and nine resistance genes, designated Dn1 to Dn9, have been identified. Another undesignated gene, Dnx, was found in the wheat accession PI220127. Mapping of the resistance genes relative to known markers will improve their use in breeding programs. The dominant RWA resistance gene, Dn5, was identified in the accession PI294994 and mapped to chromosome arm 7DL. However, recent reports have placed Dn5 on ...
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Stephens, Sarah H. "Fine mapping of the chromosome 15q13-14 schizophrenia linkage region /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.
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Thesis (Ph.D. in Human Medical Genetics) -- University of Colorado Denver, 2008.Typescript. Includes bibliographical references (leaves 112-128). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Lehmensiek, Anke. "Genetic mapping of gray leaf spot resistance genes in maize." Thesis, Stellenbosch : Stellenbosch University, 2000. http://hdl.handle.net/10019.1/51776.
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Thesis (PhD)--Stellenbosch University, 2000.ENGLISH ABSTRACT: Gray leaf spot (GLS) of maize, caused by the fungus Cercospora zeae-maydis, can reduce grain yields by up to 60% and it is now recognized as one of the most significant yield-limiting diseases of maize in many parts of the world. The most sustainable and long-term management strategy for GLS will rely heavily on the development of high-yielding, locally adapted GLS resistant hybrids. Molecular markers could be useful to plant breeders to indirectly select for genes affecting GLS resistance and to identify resistance genes without inoculation and at an early stage of plant development. Only two studies in the USA have examined quantitative trait loci (QTL) association with GLS resistance. The aim of this study was to map GLS resistance genes in a resistant Seed Co LTD, Zimbabwean inbred line. Molecular markers linked to the GLS resistance QTL were identified by using the amplified fragment length polymorphism (AFLP) technique together with bulked segregant analysis. Eleven polymorphic AFLP fragments were identified and converted to sequence-specific PCR (polymerase chain reaction) markers. Eight of the 11 converted AFLP markers were added to the maize marker database of the University of Stellenbosch. Five of the 8 converted AFLP markers were polymorphic between the resistant and the susceptible parent. They were amplified on the DNA of 230 plants of a segregating F2 population and linkage analysis was performed with MAPMAKER/EXP. Two linkage groups consisting of two markers each, with a linkage distance of 10.4 cM (LOD 22.83) and 8.2 cM (LOD 55.41) between the two markers, were identified. QTL mapping with MAPMAKER/QTL confirmed the presence of QTL in both linkage groups. Two publicly available recombinant inbred families (Burr et a/., 1988) were used to localize the converted AFLP markers on the genetic map of maize. The QTL, which were identified with the AFLP markers, were mapped to chromosomes 1 and 5. Another AFLP marker was mapped to chromosome 2 and a further to chromosome 3. To obtain more precise localizations of the QTL on chromosomes 1 and 5, sequence-tagged site markers and microsatellite markers were used. The markers were amplified on the DNA of the 230 plants of the F2 population and linkage analysis was performed with MAPMAKER/EXP. The order of the markers was in agreement with the UMC map of the Maize Genome Database. Interval mapping using MAPMAKERlQTL and composite interval mapping using QTL Cartographer were performed. The QTL on chromosome 1 had a LOD score of 21 and was localized in bin 1.05/06. A variance of 37% was explained by the QTL. Two peaks were visible for the QTL on chromosome 5, one was localized in bin 5.03/04 and the other in bin 5.05/06. Both peaks had a LOD score of 5 and 11% of the variance was explained by the QTL. To test the consistency of the detected QTL, the markers flanking each QTL were amplified on selected plants of two F2 populations planted in consecutive years and regression analysis was performed. Both the QTL on chromosome 1 and the QTL on chromosome 5 were detected in these populations. Furthermore, the presence of a QTL on chromosome 3 was confirmed with these populations. A variance of 8 -10% was explained by the QTL on chromosome 3. In this study, a major GLS resistance QTL was thus mapped on chromosomes 1 and two minor GLS resistance QTL were mapped on chromosomes 3 and 5 using a resistant Seed Co LTD, Zimbabwean inbred line. Markers were identified which could be used in a marker-assisted selection program to select for the GLS resistance QTL.
AFRIKAANSE OPSOMMING: Grys blaarvlek (GBV) van mielies, veroorsaak deur die swam Cercospora zeaemaydis, kan graanopbrengs met tot 60% verlaag en word beskou as een van die vernaamste opbrengs-beperkende siektes wêreldwyd. Die toepaslikste langtermyn stragtegie vir GBV beheer sal wees om plaaslike mieliebasters met hoë opbrengs en GBV weerstand te ontwikkel. Molekulêre merkers kan nuttig deur plantetelers gebruik word om weerstandsgene te selekteer. Seleksie is moontlik in die afwesigheid van inokolum en op 'n vroeë stadium van plant ontwikkeling. Slegs twee vorige studies (in die VSA) het kwantitatiewe-kenmerk-Iokusse (KKL), vir GBVweerstand ondersoek. Die doel van hierdie studie was om die GBV weerstandsgene in 'n weerstandbiedende ingeteelde lyn (Seed Co BPK, Zimbabwe) te karteer. Molekulêre merkers gekoppel aan die GBV weerstands KKL is geïdentifiseer deur gebruik te maak van die geamplifiseerde-fragmentlengte-polimorfisme- (AFLP-) tegniek en gebulkte-segregaat-analise. Elf polimorfiese merkers is geïdentifiseer en omgeskakel na volgorde-spesifieke PKR (polimerase kettingreaksie) merkers. Agt van die elf omgeskakelde AFLP-merkers is by die mieliemerker databasis van die Universiteit van Stellenbosch gevoeg. Vyf van die 8 omgeskakelde AFLP-merkers was polimorfies tussen die bestande en vatbare ouers. Hulle is geamplifiseer op die DNA van 230 plante van 'n segregerende F2-populasie en is gebruik in 'n koppelingstudie met MAPMAKER/EXP. Twee koppelingsgroepe, elk bestaande uit twee merkers, met onderskeidelik koppelingsafstande van 10.4 eM (LOD 22.83) en 8.2 eM (LOD 55.41) tussen die merkers, is geïdentifiseer. KKL-kartering het getoon dat KKL in albei koppelingsgroepe aanwesig is. Twee kommersieël beskikbare, rekombinant-ingeteelde families (Burr et aI., 1988) is gebruik om die omgeskakelde AFLP-merkers op die mielie genetiese kaart te plaas. Die KKL wat met die AFLP-merkers geïdentifiseer is, is gekarteer op chromosome 1 en 5. 'n Verdere AFLP-merker is op chromosoom 2 gekarteer en 'n ander op chromosoom 3. Ten einde die KKL op chromosome 1 en 5 meer akkuraat te karteer, is volgordege- etikeerde en mikrosatelliet merkers gebruik. Die merkers is geamplifiseer op die DNA van die 230 plante van die F2-populasie en koppelings-analises is uitgevoer. Die volgorde van die merkers was dieselfde as die van die UMC-kaart in die Mielie Genoom Databasis. Interval kartering met MAPMAKER/QTL en komposiet interval kartering met QTL Cartographer is uitgevoer. Die KKL op chromosoom 1 het 'n LOD-telling van 21 gehad en is in bin 1.05/06 geplaas. Die KKL was verantwoordelik vir 37% van die variansie. Twee pieke was onderskeibaar vir die KKL op chromosoom 5, een in bin 5.03/04 geleë en die ander in bin 5.05/06. Elke piek het 'n LOD-telling van 5 gehad en die twee KKL was verantwoordelik vir 11% van die variansie. Om die herhaalbaarheid van die effek van die KKL te toets is die merkers naaste aan elke KKL geamplifiseer op geselekteerde plante van twee F2-populasies wat in opeenvolgende jare geplant is. Regressie analise is op die data gedoen. Beide die KKL op chromosoom 1 en die KKL op chromosoom 5 kon in hierdie populasies geïdentifiseer word. Verder kon die aanwesigheid van 'n verdere KKL op chromosoom 3 in hierdie populasies bevestig word. Laasgenoemde KKL was verantwoordelik vir 8-10% van die totale variansie. In hierdie studie is daar dus 'n hoof GBV-weerstands KKL gekarteer op chromosoom 1 en twee kleiner GBV-weerstands KKL gekarteer op chromosome 3 en 5. Merkers is geïdentifiseer wat moontlik in merker-gebaseerdetelingsprogramme gebruik kan word om plante te selekteer wat die GBVweerstands KKL het.
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Abecasis, G. R. "Methods for fine mapping complex traits in human pedigrees." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365700.
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Djureinovic, Tatjana. "Investigation of genetic factors involved in colorectal cancer predisposition /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-864-9/.
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Dempton, Jennifer L. "Genetic intervention as a lifestyle approach an analysis of disease and treatment." Honors in the Major Thesis, University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/368.
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Purpose: The scientific knowledge of how genes affect disease expression and evolution can facilitate more effective environmental and drug therapy interventions delivered by health care professionals. The purpose of this paper is to a) describe the role of genetic science in healthcare; b) explore genotype determinants for environmental and pharmacological interventions; c) and analyze ethical dilemmas, barriers to access, and allocation of resources based on genotype. Methods: A review of literature was conducted from the disciplines of nursing, medicine, psychology, and sociology using the CINAHL, Ebsco Host, Medline, and PsychINFO databases. The search was limited to peer reviewed, full text article in English that dated from 1987 to 2011. Inclusion criteria were articles describing environmental, pharmacologic, and nutritional influence on genetic expression. Forty-five articles on genetic intervention were chosen for further review, in addition to five book publications which met inclusion criteria. Many of the sources retrieved were obtained from the biomedical sciences and published in the last decade, owing to more recent innovations in genetic discovery. Results: Disease and treatment must be approached according to genetic profiles for effectiveness and to increase health outcomes. Several variations were found regarding response to pharmaceuticals, as well as environmental exposures, based on genotype. Conclusions: Health care has been practiced using a "universal protocol" approach; however, as the literature reveals, each individual genotype must be taken into account to provide optimal care.B.S.N.
Bachelors
Nursing
Nursing
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Xiang, Fengqing. "Genetic studies of neurological disorders : Rett syndrome and HD-like familial prion disease /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4882-8/.
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Wessels, Willem Gerhardus. "Mapping genes for stem rust and Russian wheat aphid resistance in bread wheat (Triticum aestivum)." Thesis, Stellenbosch : Stellenbosch University, 1997. http://hdl.handle.net/10019.1/55580.
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Thesis ( MScAgric) -- Stellenbosch University, 1997.ENGLISH ABSTRACT: Stem rust is considered the most damaging of the wheat rusts causing yield losses of more than 50% in epidemic years. Similarly, Russian wheat aphids (RWA) can be regarded as one ofthe most devastating insect pests of wheat. Yield losses due to R W A primarily result from a reduction in plant resources (sucking plant sap). Secondary losses are incurred by viruses transmitted during feeding. Mapping disease and insect resistance genes that are effective against prevailing pathotypes and biotypes of South Africa will optimize their utilization in breeding programmes. The wheat line, 87M66-2-l, is homozygous for a single dominant stem rust resistance gene located on chromosome lD. This stem rust resistance gene has been derived from Triticum tauschii accession RL5289 and is here referred to as Srtau. The aim of this study was to determine the chromosome arm involved. Following the chromosome arm allocation of Srtau, its possible linkage with the genes Rg2, Lr 21 , Sr X and Sr 33 was studied. A telosomic analysis has shown that Srtau is located on chromosome arm 1 DS and is linked to the centromere with a recombination frequency of 21 ± 3 .40%. Glume blotch and a heavy mildew infection of segregating families planted in the field in 1996 made the linkage study between Lr 21 (leaf rust resistance) and Rg2 (glume colour) impossible. However, estimated linkages of 9 ± 1.9 map units between Sr33 (stem rust resistance) and Srtau, ± 6 map units between Sr X (stem rust resistance) and Sr 3 3 and ± 1 0 map units between Sr X and Srtau suggested that SrX, Sr33 and Srtau are closely linked on I DS. Taking existing map data into consideration, it seems that the most likely order of the genes is: centromere - Srtau - Sr 3 3 - Sr X. A single dominant R W A resistance gene, Dn5, was identified in the T aestivum accession 'SA 463' and is located on chromosome 7D. The aim ofthis study was to determine the chromosome arm involved. The possible linkage of Dn5 with the endopeptidase locus, Ep-D1 b. and chlorina mutant gene, cn-D1, was then studied. Endopeptidase zymograms of 'SA 463' revealed two unknown polymorphisms. F 2 monosomic analyses involving the chromosomes 7 A, 7B and 7D were performed in an attempt to identify the loci associated with these polymorphisms. Dn5 was mapped on chromosome arm 7DL. A recombination frequency of60 ± 4.53% between Dn5 and the centromere suggested the absence of linkage. Linkage between Ep-Dl and cn-Dl could not be calculated as a result of similar isoelectric points of the 7DL encoded endopeptidases of the parental material studied. Recombination frequencies of32 ± 4.97% between Dn5 and EpDl and 37 ± 6.30% between Dn5 and cn-Dl were, however, encountered. The two novel endopeptidase alleles encountered in 'SA 463' were designated as Ep-Dle and Ep-Ald. A RWA resistance gene was transferred from the rye accession ' Turkey 77' to wheat and in the process the RWA resistant wheat lines 91M37-7 and 91M37-51 were derived. No rye chromatin could be detected in these plants following C-banding. The aim of this study was to determine (i) on which chromosome the gene(s) is located, and (ii) whether the resistance can be the result of a small intercalary translocation of rye chromatin. A monosomic analysis of the RWA resistance gene in 91M37-51 has shown that a single dominant resistance gene occurs on chromosome 7D. The use of rye-specific dispersed probes did not reveal any polymorphisms between the negative controls and RW A resistant lines 91M3 7- 7 and 91M37-51 which would suggest that it is unlikely that the resistance was derived from rye.
AFRIKAANSE OPSOMMING: Stamroes word as die mees vemietigende graanroessiekte beskou en het in epidemiese jare oesverliese van meer as 50% tot gevolg. Russiese koringluise is eweneens een van die emstigste insekplae van koring. Russiese koringluise veroorsaak oesverliese deurdat dit plantsap uitsuig en die plant van voedingstowwe beroof. Dit tree egter ook as 'n virusvektor op en kan so indirekte oesverliese veroorsaak. Kartering van siekte- en insekweerstandsgene wat effektief is teen die Suid-Afrikaanse patotipes en biotipes, sal hulle gebruik in teelprogramme optimiseer. Die koringlyn, 87M66-2-l , is homosigoties vir 'n dominante stamroes-weerstandsgeen wat op chromosoom ID voorkom. Hierdie weerstandsgeen is uit die Triticum tauschii aanwins, RL5289, afkomstig en word hiema verwys as Srtau. Daar is gepoog om te bepaal op watter chromosoomarm Srtau voorkom, waama sy koppeling met betrekking tot die gene Rg2, Lr21 , SrX en Sr33 bepaal is. 'n Telosoomanalise het getoon dat Srtau op chromosoom-arm 1 DS voorkom en gekoppel is aan die sentromeer met 'n rekombinasie-frekwensie van 21 ± 3.40%. Segregerende populasies wat in 1996 in die land geplant is, is hewig deur aarvlek en poeieragtige meeldou besmet en dit het die moontlike bepaling van koppeling tussen Lr21 (blaarroesweerstand) en Rg2 (aarkaffie kleur) belemmer. Koppelingsafstande van 9 ± 1. 9 kaart-eenhede tussen Sr 33 (stamroesweerstand) en Srt au, ± 6 kaart -eenhede tussen Sr X ( stamroesweerstand) en Sr 3 3 en ± 1 0 kaart -eenhede tussen SrX en Srtau is geraam en toon dat SrX, Sr33 en Srtau nou gekoppel is. Die waarskynlikste volgorde van die gene op lDS is: sentromeer- Srtau- Sr33- SrX. 'n Enkele dominante Russiese koringluis-weerstandsgeen, Dn5, is in dieT aestivum aanwins 'SA 463 ' ge"identifiseer en kom op chromosoom 7D voor. Die studie het ten doel gehad om te bepaal op watter chromosoom-arm Dn5 voorkom, asook wat die koppeling van Dn5 met die endopeptidase lokus, Ep-Dl, en die chlorina mutante geen, cn-Dl , is. Endopeptidase simograrnme van 'SA 463' het twee onbekende polimorfismes getoon. Die gene wat kodeer vir hierdie twee polimorfismes is met behulp van F2 monosoom-analises wat die chromosome 7 A, 7B en 7D betrek, gei:dentifiseer. Dn5 is op chromosoom 7DL gekarteer. 'n Rekombinasie-frekwensie van 60 ± 4.53% is gevind vir die sentromeer en Dn5 en dui op die afwesigheid van koppeling. Koppeling tussen Ep-Dl en cn-Dl kon nie bepaal word nie omdat die endopeptidase bande geproduseer deur die ouerlike materiaal wat in die studie gebruik is, nie met sekerheid in die nageslag onderskei kon word nie. Rekombinasie-frekwensies van 32 ± 4.97% tussen Dn5 en Ep-Dl en 37 ± 6.30% tussen Dn5 en cn-Dl is egter bereken. Dit word voorgestel dat daar na die twee onbekende endopeptidase-allele wat in 'SA 463 ' voorkom, verwys word as Ep-Dle en Ep-Ald. 'n Russiese koringluis-weerstandsgeen is uit die rog-aanwins, 'Turkey 77', oorgedra na koring en in die proses is die Russies koringluis weerstandbiedende lyne, 91M37-7 en 91M37-51 , geproduseer. Geen rog-chromatien kon egter met behulp van C-bande in hierdie lyne waargeneem word nie. Die doel van die studie was om te bepaal (i) op watter chromosoom die geen(e) voorkom, en (ii), of die Russiese koringluis weerstandsgeen die gevolg kan wees van 'n klein interkalere translokasie van rog- chromatien. 'n Monosoom-analise van die Russiese koringluis-weerstandsgeen in 91M37-51 het getoon dat 'n enkele dominante weerstandsgeen op chromosoom 7D voorkom. Rog-spesifieke herhalende peilers het geen polimorfismes tussen negatiewe kontroles en die Russiese koringluis weerstandbiedende lyne 91M37-7 en 91M37-51 getoon nie. Dit is dus onwaarskynlik dat die weerstand in die lyne uit rog verhaal is.
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McCallion, Andrew Smyth. "Characterisation and genetic mapping of genes with potential relevance to neurodegenerative disease." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241836.
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Tamashiro-Duran, Jaqueline Hatsuko. "Alterações metabólicas cerebrais associadas aos fatores de risco cardiovascular: um estudo de tomografia por emissão de pósitron (PET)." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5142/tde-03012012-094605/.
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INTRODUÇÃO: Os fatores de risco cardiovascular (FRCV) afetam o fluxo sanguíneo cerebral, contribuindo possivelmente para o declínio cognitivo e a emergência da Doença de Alzheimer (DA), a forma mais comum de demência. A tomografia por emissão de pósitrons (positron emission tomography, PET) com fluordesoxiglucose F18 (18F-FDG) é largamente usada para demonstrar o padrão específico de metabolismo cerebral de glicose reduzido em sujeitos com DA e em indivíduos não-demenciados portadores do alelo e4 da apolipoproteína E (APOE e4), o maior fator de risco genético para DA. Entretanto, estudos de PET investigando o impacto dos FRCV no metabolismo cerebral são escassos. OBJETIVO: Examinar se níveis diferentes de FRCV estariam associados com reduções na taxa de metabolismo cerebral de glicose (TMCG), envolvendo as regiões cerebrais afetadas nos estágios iniciais da DA (pré-cúneo e giro do cíngulo posterior, neocórtex parieto-temporal lateral e região hipocampal). MÉTODOS: Nós avaliamos 59 indivíduos cognitivamente preservados (66-75 anos) subdivididos em três grupos de acordo com seu escore para Framingham Coronary Heart Disease Risk (FCHDR) (alto-risco, médio-risco e baixo-risco) para os exames de ressonância magnética (RM) e de PET-FDG. Dados de PET foram corrigidos para os efeitos de volume parcial a fim de evitar efeitos confundidores devido à atrofia cerebral regional. Nós realizamos uma análise de covariância global (ANCOVA) para investigar as reduções de TMCG em associação com os três grupos, comparações entre dois grupos para as diferenças de TMCG pelo teste-t, e índices de correlação linear voxel-a-voxel entre os valores de TMCG e escores FCHDR. Todas as análises incluíram a presença ou a ausência do APOE e4 como covariada confundidora de interesse. RESULTADOS: A investigação ANCOVA de diferenças de TMCG entre os três grupos mostraram significantes diferenças de TMCG somente no giro parahipocampal direito (p=0,032). Nas comparações entre dois grupos, reduções de TMCG significantes foram detectadas no grupo de altorisco comparado ao baixo-risco no pré-cúneo esquerdo (p=0,008) e o giro do cíngulo posterior esquerdo (p=0,007). Focos inesperados de reduções de TMCG no grupo baixo-risco comparado ao grupo alto-risco no giro parahipocampal foram detectados em ambos os hemisférios direito (p=0,001) e esquerdo (p=0,045). Havia também uma significante correlação linear positiva entre valores de TMCG e escores FCHDR no giro parahipocampal em ambos os lados direito (p=0,007) e esquerdo (p=0,025). CONCLUSÃO: Depois de controlar para a presença do APOE 4, nossos achados de hipofunção cerebral regional relacionado a FRCV mantiveram a significância estatística no pré-cúneo e no giro do cíngulo posterior, as duas regiões cerebrais onde comprometimentos funcionais são os mais consistentemente detectados nos estágios incipientes da DA. Isso sugere que os achados de hipometabolismo cerebral similares àqueles vistos nos sujeitos com DA podem ser vistos em associação com a gravidade de FRCV em amostras de indivíduos cognitivamente preservados. Uma possível explicação para o hipermetabolismo relativo no giro parahipocampal nos indivíduos com elevados FRCV seria um viés na seleção da amostra. É possível que nós tenhamos excluídos os sujeitos com os níveis mais graves de risco cardiovascular que teriam exibido os padrões de reduções de TMCG no giro parahipocampal, forçando a seleção de indivíduos que estão para o alto risco cardiovascular, mas que são capazes de exibir mecanismos compensatórios para manter o funcionamento metabólico adequado para as regiões temporolímbicas, as quais são vulneráveis às mudanças microvascularesINTRODUCTION: Cardiovascular risk factors (CVRF) are known to affect cerebral blood flow, possibly contributing to cognitive decline and to the emergence of Alzheimers disease (AD), the commonest form of dementia. Positron emission tomography (PET) with 18-fluoro-2-deoxyglucose (18FFDG) has been widely used to demonstrate specific patterns of reduced brain glucose metabolism in AD subjects and in non-demented individuals carriers of the apolipoprotein e4 allele (APOE e4), the major genetic risk factor for DA. However, PET studies investigating the impact of CVRF on cerebral metabolism have been scarce to date. OBJECTIVE: To examine whether different levels of CVRF would be associated with cerebral metabolic rate of glucose (CMRgl) reductions, involving brain regions affected in early stages of DA (precuneus and posterior cingulate gyrus, lateral temporalparietal neocortices and hippocampal region). METHODS: We assessed 59 cognitively preserved individuals (66-75 years), subdivided into three groups according to their Framingham Coronary Heart Disease Risk (FCHDR) score (high-risk, medium-risk, and low-risk), both with magnetic resonance imaging (MRI) and FDG-PET scans. PET data were corrected for partial volume effects to avoid confounding effects due to regional brain atrophy. We performed an overall analysis of covariance (ANCOVA) to investigate CMRgl reductions in association with the three groups, two-group comparisons of CMRgl differences by t-tests, and voxelwise linear correlation indices between CMRgl values and FCHDR scores. All analysis included the presence or absence of the APOE 4 allele as a confounding covariate of interest. RESULTS: The ANCOVA investigation of CMRgl differences across the three groups showed significant CMRgl differences only in the right parahippocampal gyrus (p=0.032). In the two-group comparisons, significant CMRgl reductions were detected in the high-risk group compared to the lowrisk group in the left precuneus (p=0.008); and the left posterior cingulate gyrus (p=0.007). Unexpected foci of CMRgl reductions in the low-risk compared to the high-risk group in the parahippocampal gyrus were detected, both on the right (p=0.001) and left (p=0.045) hemispheres. There was also a significant positive linear correlation between CMRgl values and FCHDR scores in the parahippocampal gyrus both for the right (p=0.007) and left (p=0.025) sides. CONCLUSION: After controlling for the presence of the APOE 4 allele, our findings of CVRF-related regional brain hypofunction retained statistical significance in the precuneus and posterior cingulate gyrus, the two brain regions where functional impairments are most consistently detected in incipient stages of AD. This suggests that findings of brain hypometabolism similar to those seen in AD subjects can be seen in association with the severity of CVRF in samples of cognitively preserved individuals. One possible explanation for the relative hypermetabolism in the parahippocampal gyrus in high CVRF individuals would be a bias in the sample selection. It is possible that we have excluded subjects with severest levels of cardiovascular risk who would have displayed patterns of reduced CMRgl in the parahippocampal gyrus, forcing the selection of individuals who are at high cardiovascular risk but are capable of displaying compensatory mechanisms to maintain adequate metabolic functioning in temporolimbic regions vulnerable to microvascular changes
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Stafford, Amanda Newland. "Physical mapping within human chromosome 11q12-q13 including the atopy locus." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239248.
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Alston, Jessica Shea. "Genetic and Functional Studies of Non-Coding Variants in Human Disease." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10515.
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Genome-wide association studies (GWAS) of common diseases have identified hundreds of genomic regions harboring disease-associated variants. Translating these findings into an improved understanding of human disease requires identifying the causal variants(s) and gene(s) in the implicated regions which, to date, has only been accomplished for a small number of associations. Several factors complicate the identification of mutations playing a causal role in disease. First, GWAS arrays survey only a subset of known variation. The true causal mutation may not have been directly assayed in the GWAS and may be an unknown, novel variant. Moreover, the regions identified by GWAS may contain several genes and many tightly linked variants with equivalent association signals, making it difficult to decipher causal variants from association data alone. Finally, in many cases the variants with strongest association signals map to non-coding regions that we do not yet know how to interpret and where it remains challenging to predict a variants likely phenotypic impact. Here, we present a framework for the genetic and functional study of intergenic regions identified through GWAS and describe application of this framework to chromosome 9p21: a non-coding region with associations to type 2 diabetes (T2D), myocardial infarction (MI), aneurysm, glaucoma, and multiple cancers. First, we compare methods for genetic fine-mapping of GWAS associations, including methods for creating a more comprehensive catalog of variants in implicated regions and methods for capturing these variants in case- control cohorts. Next, we describe an approach for using massively parallel reporter assays (MPRA) to systematically identify regulatory elements and variants across disease-associated regions. On chromosome 9p21, we fine-map the T2D and MI associations and identify, for each disease, a collection of common variants with equivalent association signals. Using MPRA, we identify hundreds of regulatory elements on chromosome 9p21 and multiple variants (including MI- and T2D-associated variants) with evidence for allelic effects on regulatory activity that can serve as a foundation for further study. More generally, the methods presented here have broad potential application to the many intergenic regions identified through GWAS and can help to uncover the mechanisms by which variants in these regions influence human disease.
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Dale, Mark. "Mapping and genetic analysis of the interleukin-1-receptor gene cluster in rheumatoid arthritis." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366156.
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Price, Sarah J. "The genetic and molecular characterization of the polycystic kidney disease-causing mouse gene BICC1." Huntington, WV : [Marshall University Libraries], 2004. http://www.marshall.edu/etd/descript.asp?ref=403.
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Thesis (Ph. D.)--Marshall University, 2004.Title from document title page. Document formatted into pages; contains p. viii, 210 p. Includes abstract. Includes bibliographical references (p. 179-204).