Academic literature on the topic 'Genome screen; Candidate gene studies'
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Journal articles on the topic "Genome screen; Candidate gene studies"
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Heward, Joanne, and Stephen C. L. Gough. "Genetic Susceptibility to the Development of Autoimmune Disease." Clinical Science 93, no. 6 (December 1, 1997): 479–91. http://dx.doi.org/10.1042/cs0930479.
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1. Autoimmune diseases are common conditions which appear to develop in genetically susceptible individuals, with expression of disease being modified by permissive and protective environments. Familial clustering and data from twin studies provided the impetus for the search for putative loci. Both the candidate gene approach in population-based case-control studies and entire genome screening in families have helped identify susceptibility genes in a number of autoimmune diseases. 2. After the first genome screen in type 1 (insulin-dependent) diabetes mellitus it seems likely that most autoimmune diseases are polygenic with no single gene being either necessary or sufficient for disease development. Of the organ-specific autoimmune diseases, genome screens have now been completed in insulin-dependent diabetes mellitus and multiple sclerosis. Furthermore, the clustering of autoimmune diseases within the same individuals suggests that the same genes may be involved in the different diseases. This is supported by data showing that both HLA (human leucocyte antigen) and CTLA-4 (cytotoxic T-lymphocyte-associated-4) appear to be involved in the development of insulin-dependent diabetes mellitus and Graves' disease. 3. Genome screens have also been completed in some of the non-organ-specific autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease and psoriasis. Many candidate genes have also been investigated although these are predominantly in population-based case-control studies. 4. Substantial progress has been made in recent years towards the identification of susceptibility loci in autoimmune diseases. The inconsistencies seen between case-control studies may largely be due to genetic mismatching between cases and controls in small datasets. Family-based association studies are being increasingly used to confirm genetic linkages and help with fine mapping strategies. It will, however, require a combination of biology and genetics, as has been necessary with the major histocompatibility complex in insulin-dependent diabetes mellitus, to identify primary aetiological mutations.
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Bischof, Jocelyn M., and Rachel Wevrick. "Genome-wide analysis of gene transcription in the hypothalamus." Physiological Genomics 22, no. 2 (July 14, 2005): 191–96. http://dx.doi.org/10.1152/physiolgenomics.00071.2005.
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As the genomic regions containing loci predisposing to obesity-related traits are mapped in human population screens and mouse genetic studies, identification of susceptibility genes will increasingly be facilitated by bioinformatic methods. We hypothesized that candidate genes can be prioritized by their expression levels in tissues of central importance in obesity. Our objective was to develop a combined bioinformatics and molecular paradigm to identify novel genes as candidates for murine or human obesity genetic modifiers based on their differential expression patterns in the hypothalamus compared with other murine tissues. We used bioinformatics tools to search publicly available gene expression databases using criteria designed to identify novel genes differentially expressed in the hypothalamus. We used RNA methods to determine their expression sites and levels of expression in the hypothalamus of the murine brain. We identified the chromosomal location of the novel genes in mice and in humans and compared these locations with those of genetic loci predisposing to obesity-related traits. We developed a search strategy that correctly identified a set of genes known to be important in hypothalamic function as well as a candidate gene for Prader-Willi syndrome that was not previously identified as differentially expressed in the hypothalamus. Using this same strategy, we identified and characterized a set of 11 genes not previously known to be differentially expressed in the murine hypothalamus. Our results demonstrate the feasibility of combined bioinformatics and molecular approaches to the identification of genes that are candidates for obesity-related disorders in humans and mice.
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Kim, Stuart K., Condor Nguyen, Andrew L. Avins, and Geoffrey D. Abrams. "Three genes associated with anterior and posterior cruciate ligament injury." Bone & Joint Open 2, no. 6 (June 1, 2021): 414–21. http://dx.doi.org/10.1302/2633-1462.26.bjo-2021-0040.r1.
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Aims The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Methods Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. Results There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Conclusion Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414–421.
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Mescheriakova, Julia Y., Annemieke JMH Verkerk, Najaf Amin, André G. Uitterlinden, Cornelia M. van Duijn, and Rogier Q. Hintzen. "Linkage analysis and whole exome sequencing identify a novel candidate gene in a Dutch multiple sclerosis family." Multiple Sclerosis Journal 25, no. 7 (June 6, 2018): 909–17. http://dx.doi.org/10.1177/1352458518777202.
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Background: Multiple sclerosis (MS) is a complex disease resulting from the joint effect of many genes. It has been speculated that rare variants might explain part of the missing heritability of MS. Objective: To identify rare coding genetic variants by analyzing a large MS pedigree with 11 affected individuals in several generations. Methods: Genome-wide linkage screen and whole exome sequencing (WES) were performed to identify novel coding variants in the shared region(s) and in the known 110 MS risk loci. The candidate variants were then assessed in 591 MS patients and 3169 controls. Results: Suggestive evidence for linkage was obtained to 7q11.22-q11.23. In WES data, a rare missense variant p.R183C in FKBP6 was identified that segregated with the disease in this family. The minor allele frequency was higher in an independent cohort of MS patients than in healthy controls (1.27% vs 0.95%), but not significant (odds ratio (OR) = 1.33 (95% confidence interval (CI): 0.8–2.4), p = 0.31). Conclusion: The rare missense variant in FKBP6 was identified in a large Dutch MS family segregating with the disease. This association to MS was not found in an independent MS cohort. Overall, genome-wide studies in larger cohorts are needed to adequately investigate the role of rare variants in MS risk.
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Samuel, Nardin, and Ivan Radovanovic. "Genetic basis of intracranial aneurysm formation and rupture: clinical implications in the postgenomic era." Neurosurgical Focus 47, no. 1 (July 2019): E10. http://dx.doi.org/10.3171/2019.4.focus19204.
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OBJECTIVEDespite the prevalence and impact of intracranial aneurysms (IAs), the molecular basis of their pathogenesis remains largely unknown. Moreover, there is a dearth of clinically validated biomarkers to efficiently screen patients with IAs and prognosticate risk for rupture. The aim of this study was to survey the literature to systematically identify the spectrum of genetic aberrations that have been identified in IA formation and risk of rupture.METHODSA literature search was performed using the Medical Subject Headings (MeSH) system of databases including PubMed, EMBASE, and Google Scholar. Relevant studies that reported on genetic analyses of IAs, rupture risk, and long-term outcomes were included in the qualitative analysis.RESULTSA total of 114 studies were reviewed and 65 were included in the qualitative synthesis. There are several well-established mendelian syndromes that confer risk to IAs, with variable frequency. Linkage analyses, genome-wide association studies, candidate gene studies, and exome sequencing identify several recurrent polymorphic variants at candidate loci, and genes associated with the risk of aneurysm formation and rupture, including ANRIL (CDKN2B-AS1, 9p21), ARGHEF17 (11q13), ELN (7q11), SERPINA3 (14q32), and SOX17 (8q11). In addition, polymorphisms in eNOS/NOS3 (7q36) may serve as predictive markers for outcomes following intracranial aneurysm rupture. Genetic aberrations identified to date converge on posited molecular mechanisms involved in vascular remodeling, with strong implications for an associated immune-mediated inflammatory response.CONCLUSIONSComprehensive studies of IA formation and rupture have identified candidate risk variants and loci; however, further genome-wide analyses are needed to identify high-confidence genetic aberrations. The literature supports a role for several risk loci in aneurysm formation and rupture with putative candidate genes. A thorough understanding of the genetic basis governing risk of IA development and the resultant aneurysmal subarachnoid hemorrhage may aid in screening, clinical management, and risk stratification of these patients, and it may also enable identification of putative mechanisms for future drug development.
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Jensen, Lea Møller, Barbara Ann Halkier, and Meike Burow. "How to discover a metabolic pathway? An update on gene identification in aliphatic glucosinolate biosynthesis, regulation and transport." Biological Chemistry 395, no. 5 (May 1, 2014): 529–43. http://dx.doi.org/10.1515/hsz-2013-0286.
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Abstract Identification of enzymes, regulators and transporters involved in different metabolic processes is the foundation to understand how organisms function. There are, however, many difficulties in identifying candidate genes as well as in proving their in vivo roles. In this review, we describe different approaches utilized in Arabidopsis thaliana to identify gene candidates and experiments required to prove the function of a given candidate. For example, we use the production of methionine-derived aliphatic glucosinolates that represent major defence compounds in A. thaliana. Nearly all biosynthetic genes, as well as the first sets of regulators and transporters, have been identified. An array of approaches, i.e. classical mapping, quantitative trait loci (QTL) mapping, eQTL mapping, co-expression, genome wide association studies (GWAS), mutant screens and phylogenetic analyses, has been exploited to increase the number of identified genes. Here we summarize the lessons learned from the different approaches used over the years with the aim to help designing and combining new approaches in the future.
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Webster, Hollie, Gabriel Keeble, Bernard Dell, John Fosu-Nyarko, Y. Mukai, Paula Moolhuijzen, Matthew Bellgard, et al. "Genome-level identification of cell wall invertase genes in wheat for the study of drought tolerance." Functional Plant Biology 39, no. 7 (2012): 569. http://dx.doi.org/10.1071/fp12083.
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In wheat (Triticum aestivum L.) drought-induced pollen sterility is a major contributor to grain yield loss and is caused by the downregulation of the cell wall invertase gene IVR1. The IVR1 gene catalyses the irreversible hydrolysis of sucrose to glucose and fructose, the essential energy substrates which support pollen development. Downregulation of IVR1 in response to drought is isoform specific and shows variation in temporal and tissue-specific expression. IVR1 is now prompting interest as a candidate gene for molecular marker development to screen wheat germplasm for improved drought tolerance. The aim of this study was to define the family of IVR1 genes to enable: (1) individual isoforms to be assayed in gene expression studies; and (2) greater accuracy in IVR1 mapping to the wheat genetic map and drought tolerance QTL analysis. Using a cell wall invertase-specific motif as a probe, wheat genomics platforms were screened for the presence of unidentified IVR1 isoforms. Wheat genomics platforms screened included the IWGSC wheat survey sequence, the wheat D genome donor sequence from Aegilops tauschii Coss, and the CCG wheat chromosome 3B assembly: contig506. Chromosome-specific sequences homologous to the query motif were isolated and characterised. Sequence annotation results showed five previously unidentified IVR1 isoforms exist on multiple chromosome arms and on all three genomes (A, B and D): IVR1–3A, IVR1–4A, IVR1–5B, IVR1.2–3B and IVR1-5D. Including three previously characterised IVR1 isoforms (IVR1.1–1A, IVR1.2–1A and IVR1.1–3B), the total number of isoform gene family members is eight. The IVR1 isoforms contain two motifs common to cell wall invertase (NDPN and WECPDF) and a high degree of conservation in exon 4, suggesting conservation of functionality. Sequence divergence at a primary structure level in other regions of the gene was evident amongst the isoforms, which likely contributes to variation in gene regulation and expression in response to water deficit within this subfamily of IVR1 isoforms in wheat.
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Sheffer, Michal, Yiguo Hu, Ophir Shalem, Neville Sanjana, Eugen Dhimolea, Subhashis Sarkar, Megan A. Bariteau, et al. "Genome-Scale Crispr-Cas9 Knockout Studies Reveal Mutifactorial and Functionally Overlapping Mechanisms of Myeloma Cell Resistance to Proteasome Inhibition." Blood 124, no. 21 (December 6, 2014): 273. http://dx.doi.org/10.1182/blood.v124.21.273.273.
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Abstract Acquired or de novo resistance to established and investigational therapies represents a major clinical challenge for multiple myeloma (MM) and other neoplasias. Despite extensive efforts, clinically-validated molecular markers that predict for proteasome inhibitor (PSI) resistance in most MM patients remain elusive. This challenge is partly due to limited availability so far of molecular data on MM patients before the start of PSI treatment vs. immediately after resistance to it develops; this challenge may also reflect the heterogeneity of the complex molecular mechanisms regulating MM cell response to PSIs. We hypothesized that resistance to PSIs can be mediated by disruption of several functionally overlapping genes, and that the prevalence of any of these lesions may be too low to detect in datasets available thus far. To examine this latter hypothesis, we performed a genome-wide screen for genes whose loss confers to MM cells resistance against bortezomib, through the use of the CRISPR (clustered regularly interspaced short palindromic repeats)–associated nuclease Cas9 system. Specifically RPMI-8226 MM cells were transduced with lentiviral construct for Cas9 nuclease, followed by lentiviral delivery of a genome-scale pooled library of 123,411 single-guide RNAs (sgRNAs), which selectively align to target sequences at the 5′ constitutive exons of 18,080 genes and direct the Cas9 nuclease to cause double-stranded cleavage and loss of function of the respective gene. From the pool of MM cells transduced with the sgRNA library and treated with bortezomib, treatment-resistant cells were processed for deep sequencing, to identify enriched sgRNAs and their corresponding genes. We identified that loss-of-function of 33 candidate genes is associated with bortezomib resistance. We observed a high level of consistency between independent sgRNAs targeting the same gene, as well as a high rate of hit confirmation across different biological replicates. Notably, this set of candidate bortezomib-resistance genes was distinct from the "hits" we identified through a parallel CRISPR screen on the same cell line for resistance to a different targeted therapy (namely the bromodomain inhibitor JQ1), supporting the ability of this approach to identify treatment-specific resistance genes. These candidate bortezomib-resistance genes have documented or presumed roles in the regulation of extrinsic and intrinsic apoptotic cascades, autophagy, Toll-like receptor and NF-kappaB signaling, aggresome function, heat shock protein expression, chromatin remodeling, nutrient sensing, and tumor suppressor gene networks. Importantly, information from several publically available molecular profiling datasets converge to support the putative clinical relevance of these genes. For instance, gene expression data from tumor cells of bortezomib-naive patients with advanced MM revealed several transcriptional signatures of these candidate genes (defined by low transcript levels for any of the genes in the signature) which correlated with shorter time to disease progression after treatment with bortezomib (p<0.01, log-rank test), but not dexamethasone (p>0.426). Congruent with these findings, the highly bortezomib-responsive clinical setting of newly-diagnosed MM is associated with low cumulative frequency of mutations of these bortezomib-resistance genes (e.g. cumulative mutation rate of 3.9%, 95% confidence interval [CI] 1.25-6.55%). Notably, in other malignancies that are typically PSI-resistant, a higher cumulative frequency of such lesions is observed (average of ~28%, range 0-76%, 95% CI 22.46-32.70%; 57 datasets from 20+ neoplasias examined). In summary, this first application of the CRISPR/Cas9-based technology in MM illustrates its power to interrogate gene function on a genome-wide scale. This approach identifies bortezomib-resistance genes that are associated with pathways linked with the regulation of proteasome inhibitor response. Results from molecularly-annotated clinical samples converge to support a possible role for these genes in bortezomib resistance. This experience supports the value of CRISPR/Cas9-based studies to dissect the molecular mechanisms of treatment resistance in MM and other hematologic neoplasias (* equal contribution of M.S. and Y.H.). Disclosures Shalem: Broad Institute: Patent application for CRISPR technology Patents & Royalties. Sanjana:Broad Institute: Patent application for CRISPR technology Patents & Royalties. Zhang:Broad Institute: Patent application for CRISPR technology Patents & Royalties. Mitsiades:Johnson & Johnson: Research Funding; Amgen: Research Funding; Celgene: Consultancy, Honoraria; Millennium Pharmaceuticals: Consultancy, Honoraria.
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DOU, BINGDE, BEIWEI HOU, HAIMING XU, XIANGYANG LOU, XIAOFEI CHI, JINBIN YANG, FANG WANG, ZHONGFU NI, and QIXIN SUN. "Efficient mapping of a female sterile gene in wheat (Triticum aestivum L.)." Genetics Research 91, no. 5 (October 2009): 337–43. http://dx.doi.org/10.1017/s0016672309990218.
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SummaryStudies on inheritance of fertility are of great importance in wheat breeding. Although substantial progress has been achieved in molecular characterization of male sterility and fertility restoration recently, little effort has been devoted to female sterility. To identify the gene(s) controlling female sterility in wheat efficiently, an investigation was conducted for the seed setting ratio using a set of F2 populations derived from the cross between a female sterile line XND126 and an elite cultivar Gaocheng 8901. Bulked segregation analysis (BSA) method and recessive class approach were adopted to screen for SSR markers potentially linked to female fertility gene loci in 2005. Out of 1080 SSRs in wheat genome, eight markers on chromosome 2D showed a clear difference between two disparate bulks and small recombination frequency values, suggesting a strong linkage signal to the sterility gene. Based on the candidate linked markers, partial linkage maps were constructed with Mapmaker 3.0 (EXP) instead of whole genome maps, and quantitative trait locus (QTL) mapping was implemented with software QTLNetwork 2.0. A major gene locus designated as taf1, was located on chromosome 2DS. The above result was confirmed by the analysis for 2007 data, and taf1 was identified on the same chromosome 2DS with a confidence interval of 2·4 cM, which could explain 44·99% of phenotypic variation. These results provided fundamental information for fine mapping studies and laid the groundwork for wheat fertility genetic studies.
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Slof-Op ‘t Landt, Margarita C. T., Eric F. van Furth, Ingrid Meulenbelt, P. Eline Slagboom, Meike Bartels, Dorret I. Boomsma, and Cynthia M. Bulik. "Eating Disorders: From Twin Studies to Candidate Genes and Beyond." Twin Research and Human Genetics 8, no. 5 (October 1, 2005): 467–82. http://dx.doi.org/10.1375/twin.8.5.467.
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AbstractSubstantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.
Dissertations / Theses on the topic "Genome screen; Candidate gene studies"
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Meisner, Sarah. "The genetics of susceptibility to leprosy." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298995.
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DuPree, Michael G. "A candidate gene study and a full genome screen for male homosexuality." Connect to this title online, 2002. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-209/index.html.
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Mountjoy, Edward John. "Genome-wide and candidate-gene association studies of visual and cognitive phenotypes and their inter-relationships." Thesis, University of Bristol, 2018. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.743031.
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Muiños, Gimeno Margarita. "Analysis of genetic variation in microrna-mediated regulation and the susceptibility to anxiety disorders." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7192.
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We have investigated genetic variation in microRNA-mediated regulation as a susceptibility factor for anxiety disorders following two different approaches. We first studied two isoforms of the candidate gene NTRK3 by re-sequencing its different 3'UTRs in patients with Panic (PD) and Obsessive Compulsive disorders (OCD) as well as controls. Two rare variants that altered microRNA-mediated regulation were identified in PD. Conversely, association of a common SNP with OCD hoarding subtype was found. Moreover, we have also studied a possible involvement of microRNAs in anxiety disorders. Consequently, we have analysed the genomic organisation and genetic variation of miRNA-containing regions to construct a panel of SNPs for association analysis. Case-control studies revealed several associations. However, it is worth remarking the associations of miR-22 and miR-488 with PD; two microRNAs for which functional assays and transcriptome analysis after microRNA overexpression showed significant repression of a subset of genes involved in physiological pathways linked to PD development.Hem investigat la variació genètica a la regulació mediada per microRNAs com a factors de susceptibilitat pels trastorns d'ansietat seguint dues aproximacions diferents. Primer vam estudiar dues isoformes del gen candidat NTRK3 mitjançant la reseqüenciació dels seus diferents 3'UTRs a pacients de pànic (TP), a pacients amb trastorn obsessiu compulsiu (TOC) i a controls. Dues variants rares que alteren la regulació mediada per microRNAs foren identificades per TP. D'altra banda, es trobà associació d'un SNP comú amb el subtipus acumulador de TOC. A més, també hem estudiat la possible implicació dels microRNAs als trastorns d'ansietat. Conseqüentment, hem analitzat l'organització genòmica i la variació genètica a regions que contenen microRNAs per construir un panell d'SNPs per fer anàlisis d'associació. Els estudis cas-control van revelar algunes associacions. Tanmateix, val la pena destacar les associacions del miR-22 i el miR-488 amb TP; dos microRNAs pels quals assajos funcionals i anàlisis de transcriptoma després de la seva sobreexpressió han mostrat una repressió significativa d'un grup de gens implicats en vies fisiològiques lligades al desenvolupament del TP.
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"Candidate gene study of predisposition to tuberculosis in the era of genome-wide association studies." 2011. http://library.cuhk.edu.hk/record=b5894758.
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Wang, Xingyan.Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 126-131).
Abstracts in English and Chinese.
ACKNOWLEDGEMENT --- p.I
ABBREVIATIONS --- p.II
ABSTRACT --- p.V
摘要 --- p.VIII
Chapter CHAPTER 1 --- INTRODUCTION --- p.1
Chapter 1.1 --- CLINICAL DISEASE CAUSED BY M.TB --- p.1
Chapter 1.1.1 --- Tuberculosis (TB) --- p.1
Chapter 1.1.2 --- Pathogen: Mycobacteria tuberculosis (M. TB) --- p.2
Chapter 1.2 --- HOST DEFENSE AGAINST M.TB --- p.4
Chapter 1.2.1 --- Overview --- p.4
Chapter 1.2.2 --- Specific pathways --- p.6
Chapter 1.3 --- GENETIC PREDISPOSITION OF HOST TO INFECTION --- p.12
Chapter CHAPTER 2 --- OVERVIEW AND AIM OF THIS PROJECT --- p.14
Chapter 2.1 --- GWAS REPLICATION --- p.14
Chapter 2.2 --- CANDIDATE GENES REVEALED IN GWAS OF OTHER GRANULOMATOUS INFLAMMATORY DISEASES (GLD) --- p.14
Chapter 2.3 --- CHROMOSOME 17 CHEMOKINE CLUSTER REGION --- p.15
Chapter CHAPTER 3 --- REPLICATION STUDY OF TB GWAS --- p.16
Chapter 3.1 --- INTRODUCTION --- p.16
Chapter 3.1.1 --- TB GWAS study --- p.16
Chapter 3.1.2 --- Aims of this part --- p.16
Chapter 3.2 --- MATERIAL AND METHODS --- p.17
Chapter 3.2.1 --- Case and control samples --- p.17
Chapter 3.2.2 --- DNA extraction --- p.18
Chapter 3.2.3 --- Genotyping of the SNPs --- p.19
Chapter 3.2.4 --- Statistical analysis --- p.21
Chapter 3.3 --- RESULTS --- p.23
Chapter 3.3.1 --- Description of studied samples --- p.23
Chapter 3.3.2 --- Results of case-control study for replication studies of TB GWAS --- p.23
Chapter 3.4 --- DISCUSSION --- p.28
Chapter CHAPTER 4 --- GENETIC VARIANTS IN GRANULOMATOUS INFLAMMATORY DISEASES --- p.32
Chapter 4.1 --- INTRODUCTION --- p.32
Chapter 4.1.1 --- Granulomatous inflammation --- p.32
Chapter 4.1.2 --- Diseases characterized by granulomatous inflammatory --- p.34
Chapter 4.1.3 --- Shared immune mechanisms in GiDs --- p.38
Chapter 4.1.4 --- Genome-wide Association Studies (GWAS) in GiD --- p.38
Chapter 4.1.5 --- Hypothesis of this part --- p.41
Chapter 4.2 --- MATERIAL AND METHODS --- p.43
Chapter 4.2.1 --- Case and control samples --- p.43
Chapter 4.2.2 --- DNA extraction --- p.44
Chapter 4.2.3 --- Tag SNP selection --- p.44
Chapter 4.2.4 --- Genotyping of tagging SNPs --- p.45
Chapter 4.2.5 --- Statisitical analysis --- p.45
Chapter 4.3 --- RESULTS --- p.55
Chapter 4.3.1 --- Description of TB case samples --- p.55
Chapter 4.3.2 --- Primary endpoint case-control results --- p.56
Chapter 4.3.3 --- Secondary endpoint case-only studies results --- p.67
Chapter 4.3.4 --- Haplotype analysis --- p.78
Chapter 4.4 --- DISCUSSION --- p.83
Chapter 4.4.1 --- ATG16L1 gene with TB susceptibility --- p.83
Chapter 4.4.2 --- Associations in case-only studies (Interaction effects) --- p.83
Chapter 4.4.2.1 --- Age and pathogenesis of TB --- p.83
Chapter CHAPTER 5 --- STUDIES IN THE CHEMOKINE-GENE CLUSTER AND A MIRNA SNP STUDY --- p.89
Chapter 5.1 --- INTRODUCTION --- p.89
Chapter 5.1.1 --- Genetic susceptibility to TB in familial cases --- p.89
Chapter 5.1.2 --- Familial studies suggested linkage at 17qll.2 --- p.89
Chapter 5.1.3 --- Chemokines --- p.90
Chapter 5.1.4 --- Studies of SNP rs2910164 of microRNA-146a (miRNA-146a) --- p.91
Chapter 5.2 --- MATERIAL AND METHODS --- p.92
Chapter 5.2.1 --- Case and control samples --- p.92
Chapter 5.2.2 --- DNA extraction --- p.92
Chapter 5.2.3 --- TagSNP selection --- p.92
Chapter 5.2.4 --- Genotyping of tagging SNPs --- p.93
Chapter 5.2.5 --- PCR-RFLP --- p.93
Chapter 5.2.6 --- Statistical analysis --- p.94
Chapter 5.3 --- RESULTS --- p.100
Chapter 5.3.1 --- PCR-RFLP results of the three SNPs --- p.100
Chapter 5.3.2 --- Description of TB case samples --- p.102
Chapter 5.3.3 --- Primary endpoint case-control results --- p.103
Chapter 5.3.4 --- Secondary endpoint case-only studies results of CCL genes --- p.109
Chapter 5.4 --- DISCUSSION --- p.120
Chapter 5.4.1 --- Genetic association of SNPs with severity of TB --- p.120
Chapter 5.4.2 --- Smoking and immunity --- p.121
Chapter CHAPTER 6 --- FINAL CONCLUSION AND PROSPECT FOR FUTURE WORK --- p.122
Chapter 6.1 --- CONCLUSION --- p.122
Chapter 6.2 --- LIMITATION OF THE STUDIES --- p.124
Chapter 6.3 --- FUTURE WORKS AND PROSPECT --- p.125
REFERENCES --- p.126
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Li, X., X. Zhou, Yonghong Peng, B. Liu, R. Zhang, J. Hu, J. Yu, C. Jia, and C. Sun. "Network based integrated analysis of phenotype-genotype data for prioritization of candidate symptom genes." 2014. http://hdl.handle.net/10454/10724.
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YesSymptoms and signs (symptoms in brief) are the essential clinical manifestations for individualized diagnosis and treatment in traditional Chinese medicine (TCM). To gain insights into the molecular mechanism of symptoms, we develop a computational approach to identify the candidate genes of symptoms. This paper presents a network-based approach for the integrated analysis of multiple phenotype-genotype data sources and the prediction of the prioritizing genes for the associated symptoms. The method first calculates the similarities between symptoms and diseases based on the symptom-disease relationships retrieved from the PubMed bibliographic database. Then the disease-gene associations and protein-protein interactions are utilized to construct a phenotype-genotype network. The PRINCE algorithm is finally used to rank the potential genes for the associated symptoms. The proposed method gets reliable gene rank list with AUC (area under curve) 0.616 in classification. Some novel genes like CALCA, ESR1, and MTHFR were predicted to be associated with headache symptoms, which are not recorded in the benchmark data set, but have been reported in recent published literatures. Our study demonstrated that by integrating phenotype-genotype relationships into a complex network framework it provides an effective approach to identify candidate genes of symptoms.
NSFC Project (61105055, 81230086), China 973 Program (2014CB542903), The National Key Technology R&D Program (2013BAI02B01, 2013BAI13B04), the National S&T Major Special Project on Major New Drug Innovation (2012ZX09503-001-003), and the Fundamental Research Funds for the Central Universities.
Books on the topic "Genome screen; Candidate gene studies"
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The Genetics of Sjogren's Syndrom: Candidate Gene Analyses and Genome-wide Linkage Studies. University of Bergen, 2002.
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Haiman, Christopher, and David J. Hunter. Genetic Epidemiology of Cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780190676827.003.0004.
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This chapter explores the genetic epidemiology of cancer: the identification and quantification of inherited genetic factors, and their potential interaction with the environment, in the etiology of cancer in human populations. It also describes the techniques used to identify genetic variants that contribute to cancer susceptibility. It describes the older research methods for identifying the chromosomal localization of high-risk predisposing genes, such as linkage analysis within pedigrees and allele-sharing methods, as it is important to understand the foundations of the field. It also reviews the epidemiologic study designs that can be helpful in identifying low-risk alleles in candidate gene and genome-wide association studies, as well as gene–environment interactions. Finally, it describes some of the genotyping and sequencing platforms commonly employed for high-throughput genome analysis, and the concept of Mendelian randomization and how it may be useful in the study of biomarkers and environmental causes of cancer.
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Sumner, Jennifer A., Angela C. Bustamante, Karestan C. Koenen, and Monica Uddin. Genetics of PTSD. Edited by Israel Liberzon and Kerry J. Ressler. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190215422.003.0011.
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Trauma exposure and PTSD are heritable. However, the mechanisms of risk and resilience following trauma exposure are not yet well understood, suggesting that investigations into the genetic architecture of PTSD have much to contribute. This chapter reviews the rapidly growing literature on molecular genetic risk factors for PTSD, including findings from candidate gene and genome-wide association studies. Given the critical role of trauma exposure in the onset of PTSD, it also discusses gene-environment interplay, and highlights some recent findings from epigenetic studies. The chapter concludes by summarizing considerations for the field as it continues to move forward, and discusses exciting new developments in the search for genetic markers for PTSD.
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Hinks, Anne, and Wendy Thomson. Genetics of juvenile rheumatic diseases. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199642489.003.0043_update_002.
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Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and large-scale genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now 17 JIA susceptibility loci which reach the genome-wide significance threshold for association and a further 7 regions with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
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Hinks, Anne, and Wendy Thomson. Genetics of juvenile rheumatic diseases. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199642489.003.0043_update_003.
Full textAbstract:
Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and large-scale genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now 17 JIA susceptibility loci which reach the genome-wide significance threshold for association and a further 7 regions with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
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MacGregor, Alex, Ana Valdes, and Frances M. K. Williams. Genetics of osteoarthritis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0044.
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In this chapter we outline the approaches which have been adopted to identify genetic variants predisposing to osteoarthritis (OA), a condition long recognized as having a heritable component. Such routes to their identification include examining mendelian traits in which OA is a feature, candidate gene studies based on knowledge of OA pathobiology, linkage analysis in related individuals, and, more recently, genome-wide association studies in large samples of unrelated individuals. It is increasingly evident that the main symptom deriving from OA—notably joint pain—also has a genetic basis but this is differs from that underlying OA. Variants convincingly shown to predispose to OA lie in the GDF5 and MCF2L genes and in the chr7 cluster mapping to the COG5 gene, in addition to the ASPN gene in Asian populations. Those associated with pain in OA include TRPV1 and PACE4. Epigenetic influences are also being explored in both the pathogenesis of OA and the variation of pain processing.
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Arnold, Paul. Genetics of OCD. Edited by Christopher Pittenger. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190228163.003.0019.
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Obsessive-compulsive disorder (OCD) often runs in families and has been shown to have significant heritability. It is genetically complex, and two decades of genetic work have not converged on a clear understanding of genetic risk factors. However, accelerating progress in recent years has begun to generate some insights into the genetic architecture of the disorder, and greater clarity is likely to emerge in the coming decade. This chapter summarizes several lines of genetic work, including genome-wide genetic and linkage studies; candidate gene studies; and investigations of gene-environment interactions and of pharmacogenetics. One developing theme is that genetic variance in components of the brain’s glutamate signaling system may contribute to the development of OCD. Advancing understanding of the genetics of OCD may lead to new insights into pathobiology and to new tools to optimize individual treatment.
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Distel, Marijn A., and Marleen H. M. de Moor. Genetic Influences on Borderline Personality Disorder. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199997510.003.0007.
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Borderline personality disorder (BPD) tends to “run in families.” Twin and twin family studies show that BPD is moderately heritable, with some evidence for nonadditive gene action. BPD co-occurs with Axis I and other Axis II disorders, as well as with a certain profile of normal personality traits. Multivariate twin (family) studies have shown that these phenotypic associations are partly due to genetic associations, and this is observed most strongly for BPD and neuroticism. Candidate gene-finding studies for BPD suggest the possible role of genes in the serotonergic and dopaminergic system, but this needs to be confirmed in larger genome-wide studies. Future studies will complement the knowledge described in this chapter to enable us to move toward a comprehensive model of the development of BPD in which biological and environmental influences on BPD are integrated.
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Goldman, David, Zhifeng Zhou, and Colin Hodgkinson. The Genetic Basis of Addictive Disorders. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0042.
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Addictive disorders are moderately to highly heritable, indicating that alleles transmitted from parents are protective, or enhance risk by whatever mechanisms. However, the inheritance of addictive disorders is complex, involving hundreds of genes and variants that are both common and rare, and that vary in effect size and context of action. Genes altering risk for addictions have been identified by pathway and candidate gene studies in humans and model organisms, and genomic approaches including genome-wide association, meiotic linkage, and sequencing. Genes responsible for shared liability to different addictive disorders have been identified, as well as genes that are relatively specific in altering risk of addiction to one agent. An impediment to overarching conclusions is that most of the heritability of addictions is unexplained at the level of gene or functional locus. However, new analytic approaches and tools have created new potentials for resolution of the “missing heritability.”
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Hinks, Anne, and Wendy Thomson. Genetics of juvenile rheumatic diseases. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0043.
Full textAbstract:
Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now an additional 12 JIA susceptibility loci with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
Book chapters on the topic "Genome screen; Candidate gene studies"
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Haller, József. "Neurogenetics, Genome-Wide Association and Candidate Gene Studies." In Neurobiopsychosocial Perspectives on Aggression and Violence, 67–126. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-46331-1_3.
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Nolte, Ilja M., Jeanne M. McCaffery, and Harold Snieder. "Candidate Gene and Genome-Wide Association Studies in Behavioral Medicine." In Handbook of Behavioral Medicine, 423–41. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-0-387-09488-5_29.
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Vaxillaire, Martine, and Philippe Froguel. "The Genetics of Type 2 Diabetes: From Candidate Gene Biology to Genome-Wide Studies." In Textbook of Diabetes, 191–214. Oxford, UK: Wiley-Blackwell, 2010. http://dx.doi.org/10.1002/9781444324808.ch12.
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Canli, Turhan. "Molecular Trait Psychology." In Using Basic Personality Research to Inform Personality Pathology, edited by Douglas B. Samuel and Donald R. Lynam, 237–54. Oxford University Press, 2019. http://dx.doi.org/10.1093/med-psych/9780190227074.003.0011.
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This chapter discusses the field of molecular psychology, which applies the tools of molecular biology (e.g., candidate gene studies, genome-wide association studies, optogenetics, genome editing) to the study of behavior and its underlying neural structures and functions. Specifically, the chapter reports on research that applies these tools to personality traits.
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Mogil, Jeffrey S. "Genetics and pain in childhood." In Oxford Textbook of Pediatric Pain, edited by Bonnie J. Stevens, Gareth Hathway, and William T. Zempsky, 79–86. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198818762.003.0009.
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Genomic and other “omic” approaches are now routinely applied to the study of pain. Some of these investigations have utilized pediatric populations. This review describes what is currently known about the heritability of pain in children (from twin studies), genes relevant to pain in children (from single-gene mutations, candidate gene, and genome-wide association studies), and the application of newer techniques, such as epigenomics, to pediatric pain.
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Cutter, Asher D. "Case studies in molecular population genetics." In A Primer of Molecular Population Genetics, 195–216. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198838944.003.0009.
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Collections of DNA from nature for many individuals and loci give us the raw material for studying evolution at the molecular level. Chapter 9, “Case studies in molecular population genetics: genotype to phenotype to selection,” dives into several case studies of exciting real-world organisms that demonstrate the application from A to Z of the concepts developed throughout the book. It includes summaries of the natural context for each organism, ranging from armoring in fish (Eda, Pitx1) and color crypsis in mice (Mc1r) to butterfly flight ability (Pgi) and toxin metabolism in Drosophila fruit flies (Cyp6g1, Adh), then walks through the molecular data, their visualization, and their analysis. Complications and caveats to real-world analysis are discussed for how to identify demographic and selective effects in empirical datasets. The approaches include both candidate gene studies and genome scans, and show how different molecular population genetic analyses work in concert with one another. These population genetic analyses also can dovetail with functional molecular genetic experiments and with genetic mapping using crosses or genome-wide association study analysis. Chapter 9 ends by introducing a summary of several advanced topics in molecular population genetics, including concepts and tests for selection on standing variation, the genomic scale of data computation and evolutionary modelling, and connections to human evolution.
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Kendall, Kimberley M., James T. R. Walters, and Michael C. O’Donovan. "Genetics of schizophrenia." In New Oxford Textbook of Psychiatry, edited by John R. Geddes, Nancy C. Andreasen, and Guy M. Goodwin, 587–96. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198713005.003.0059.
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This chapter on genetics of schizophrenia briefly summarizes the key findings from genetic epidemiology and the early, but largely unsuccessful, findings from molecular genetics, based on linkage and candidate gene studies. It then reviews in detail the contemporary findings from genome-wide studies of the disorder, including those from genome-wide association studies (GWAS) of common variation, copy number variant studies (CNV) of rare variation, and exome-wide sequencing studies. It considers the implications of these studies with respect to pathophysiology, the relationship between schizophrenia and other psychiatric disorders, and the current clinical implications of the findings.
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Eastman, Meridith L., Ashlee A. Moore, and Roxann Roberson-Nay. "Genetics of Pediatric Irritability." In Irritability in Pediatric Psychopathology, edited by Amy Krain Roy, Melissa A. Brotman, and Ellen Leibenluft, 149–70. Oxford University Press, 2019. http://dx.doi.org/10.1093/med-psych/9780190846800.003.0008.
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This chapter provides an overview of behavioral and molecular genetics of pediatric irritability. Literature searches using PubMed and PsycInfo databases yielded 37 relevant animal and human studies on irritability. Studies of rodent and primate models initially suggested a genetic etiology for the trait and influenced selection of candidate genes for study in human studies. Behavioral genetic studies of irritability suggest that pediatric irritability is likely influenced by additive genetic and nonshared unique environmental factors, with little to no influence of dominant genetic or shared family environmental factors. Molecular genetic studies have been largely limited to candidate genes with a few emerging genome-wide association studies (GWAS). Results from the candidate gene literature on irritability are inconclusive, and GWAS in clinical populations has yielded limited findings. Future genetic studies of irritability would benefit from the use of appropriate phenotypic measures, adequate sample sizes, and multimethod and longitudinal approaches.
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I. Udoh, Lovina, Willie Peggy Obaseojei, and Chiebuka Uzoebo. "Single Nucleotide Polymorphisms: A Modern Tool to Screen Plants for Desirable Traits." In Plant Breeding - Current and Future Views. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94935.
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Single nucleotide polymorphism (SNP) represent a change in a single nucleotide within the genome. This can alter the phenotype of an individual within the same species if it occurs in a coding region of the gene. The change in nucleotide can produce desirable characteristic in plants and can become an object for selection. New SNPs have been discovered and subsequently converted to molecular markers using various non-gel based and next generation sequencing platforms. Considering that SNP markers are based on target genes, its abundance in the genome, high automation and multiplexability, has made it a marker of choice and an effective tool for screening plant germplasm for desirable traits. This chapter considers SNP as molecular marker, their discovery and different SNP genotyping methods was documented. A few case studies of SNP as allele specific markers and their association with traits of interest was considered. Thus, highlighting their efficacy as useful tool for marker assisted selection and plant germplasms screening.
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Halldorsdottir, Thorhildur, and Hildur Ýr Hilmarsdottir. "Genetic Risk Factors of Depression." In Depression, edited by Sonia Israel, David Benrimoh, Sylvanne Daniels, and Gustavo Turecki, 33–50. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780190929565.003.0003.
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Research on the genetic underpinnings of depression has rapidly advanced in the past decade. This field of research provides a promising avenue toward improving the diagnosis of, prevention of, and treatment for this devastating disorder. The goal of this chapter is to review the main genetic and gene-by-environment interaction findings on depression. We first describe family and twin studies used to empirically study the familial aggregation of depression. Second, we provide a review of the genome-wide association studies (GWAS) published to date. Building on GWAS findings, we will discuss the use of polygenic risk scores in predicting depression. We also review the most robust candidate gene studies and gene-by-environment interaction studies. Finally, we discuss the clinical implications of the findings and promising strategies for making further progress within this field.