Academic literature on the topic 'Allele variances'
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Journal articles on the topic "Allele variances"
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Wang, Jinliang. "An Estimator for Pairwise Relatedness Using Molecular Markers." Genetics 160, no. 3 (March 1, 2002): 1203–15. http://dx.doi.org/10.1093/genetics/160.3.1203.
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Abstract I propose a new estimator for jointly estimating two-gene and four-gene coefficients of relatedness between individuals from an outbreeding population with data on codominant genetic markers and compare it, by Monte Carlo simulations, to previous ones in precision and accuracy for different distributions of population allele frequencies, numbers of alleles per locus, actual relationships, sample sizes, and proportions of relatives included in samples. In contrast to several previous estimators, the new estimator is well behaved and applies to any number of alleles per locus and any allele frequency distribution. The estimates for two- and four-gene coefficients of relatedness from the new estimator are unbiased irrespective of the sample size and have sampling variances decreasing consistently with an increasing number of alleles per locus to the minimum asymptotic values determined by the variation in identity-by-descent among loci per se, regardless of the actual relationship. The new estimator is also robust for small sample sizes and for unknown relatives being included in samples for estimating allele frequencies. Compared to previous estimators, the new one is generally advantageous, especially for highly polymorphic loci and/or small sample sizes.
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Zeng, Z. B., D. Houle, and C. C. Cockerham. "How informative is Wright's estimator of the number of genes affecting a quantitative character?" Genetics 126, no. 1 (September 1, 1990): 235–47. http://dx.doi.org/10.1093/genetics/126.1.235.
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Abstract S. Wright suggested an estimator, m, of the number of loci, m, contributing to the difference in a quantitative character between two differentiated populations, which is calculated from the phenotypic means and variances in the two parental populations and their F1 and F2 hybrids. The same method can also be used to estimate m contributing to the genetic variance within a single population, by using divergent selection to create differentiated lines from the base population. In this paper we systematically examine the utility and problems of this technique under the influences of unequal allelic effects and initial allele frequencies, and linkage, which are known to lead m to underestimate m. In addition, we examine the effects of population size and selection intensity during the generations of selection. During selection, the estimator m rapidly approaches its expected value at the selection limit. With reasonable assumptions about unequal allelic effects and initial allele frequencies, the expected value of m without linkage is likely to be on the order of one-third of the number of genes. The estimates suffer most seriously from linkage. The practical maximum expectation of m is just about the number of chromosomes, considerably less than the "recombination index" which has been assumed to be the upper limit. The estimates are also associated with large sampling variances. An estimator of the variance of m derived by R. Lande substantially underestimates the actual variance. Modifications to the method can ameliorate some of the problems. These include using F3 or later generation variances or the genetic variance in the base population, and replicating the experiments and estimation procedure. However, even in the best of circumstances, information from m is very limited and can be misleading.
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Yi, Nengjun, and Shizhong Xu. "A Random Model Approach to Mapping Quantitative Trait Loci for Complex Binary Traits in Outbred Populations." Genetics 153, no. 2 (October 1, 1999): 1029–40. http://dx.doi.org/10.1093/genetics/153.2.1029.
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Abstract Mapping quantitative trait loci (QTL) for complex binary traits is more challenging than for normally distributed traits due to the nonlinear relationship between the observed phenotype and unobservable genetic effects, especially when the mapping population contains multiple outbred families. Because the number of alleles of a QTL depends on the number of founders in an outbred population, it is more appropriate to treat the effect of each allele as a random variable so that a single variance rather than individual allelic effects is estimated and tested. Such a method is called the random model approach. In this study, we develop the random model approach of QTL mapping for binary traits in outbred populations. An EM-algorithm with a Fisher-scoring algorithm embedded in each E-step is adopted here to estimate the genetic variances. A simple Monte Carlo integration technique is used here to calculate the likelihood-ratio test statistic. For the first time we show that QTL of complex binary traits in an outbred population can be scanned along a chromosome for their positions, estimated for their explained variances, and tested for their statistical significance. Application of the method is illustrated using a set of simulated data.
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Qing-Quan, Chen, Yu Si-Bin, Li Chun-Hai, and Mou Tong-Min. "QTL identification for seed setting rate of rice in various environments." Chinese Journal of Agricultural Biotechnology 4, no. 3 (December 2007): 239–45. http://dx.doi.org/10.1017/s1479236207001970.
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AbstractTo understand the genetic basis of seed setting rate (SSR) in rice, two breeding lines (Oryza sativa ssp. indica), T226 with higher and stable SSR and T219 with lower and fluctuating SSR from different natural conditions, were used for constructing recombinant inbred lines (RILs). Genotype by environment (G×E) interaction and quantitative trait loci (QTL) for SSR were analysed using a population with 202 RILs under eight differing environments. A significant G×E interaction for SSR was detected in rice using the Additive Main Effects and Multiplicative Interaction (AMMI) statistical model, and the IPCA1 and IPCA2 of the G×E interaction accounted for a variation of 57.6%. QTL controlling the SSR were detected by the method of interval analysis. Seventeen QTL on nine chromosomes were identified across eight environments, totally explaining the phenotypic variances from 4.6 to 35.7%. Most of the QTL, each explaining a small part of the phenotypic variances and interacting with environments, were detected in one or two environments, and their alleles for increasing the SSR were derived from T226. However, the QTL (MRG5959–MRG2180) on chromosome 3 was detected across six different environments. It explained maximum phenotypic variances in each detected environment and its allele for increasing the SSR was derived from T226. Another QTL, mapped between markers RM592 and RM169 on chromosome 5, was detected in five various environments and its allele increasing the SSR was derived from T219.
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Zeng, Z. B., and C. C. Cockerham. "Variance of neutral genetic variances within and between populations for a quantitative character." Genetics 129, no. 2 (October 1, 1991): 535–53. http://dx.doi.org/10.1093/genetics/129.2.535.
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Abstract The variances of genetic variances within and between finite populations were systematically studied using a general multiple allele model with mutation in terms of identity by descent measures. We partitioned the genetic variances into components corresponding to genetic variances and covariances within and between loci. We also analyzed the sampling variance. Both transient and equilibrium results were derived exactly and the results can be used in diverse applications. For the genetic variance within populations, sigma 2 omega, the coefficient of variation can be very well approximated as [formula: see text] for a normal distribution of allelic effects, ignoring recurrent mutation in the absence of linkage, where m is the number of loci, N is the effective population size, theta 1(0) is the initial identity by descent measure of two genes within populations and t is the generation number. The first term is due to genic variance, the second due to linkage disequilibrium, and third due to sampling. In the short term, the variation is predominantly due to linkage disequilibrium and sampling; but in the long term it can be largely due to genic variance. At equilibrium with mutation [formula: see text] where u is the mutation rate. The genetic variance between populations is a parameter. Variance arises only among sample estimates due to finite sampling of populations and individuals. The coefficient of variation for sample gentic variance between populations, sigma 2b, can be generally approximated as [formula: see text] when the number of loci is large where S is the number of sampling populations.
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Easteal, Simon. "THE ECOLOGICAL GENETICS OF INTRODUCED POPULATIONS OF THE GIANT TOAD BUFO MARINUS. II. EFFECTIVE POPULATION SIZE." Genetics 110, no. 1 (May 1, 1985): 107–22. http://dx.doi.org/10.1093/genetics/110.1.107.
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ABSTRACT The allele frequencies are described at ten polymorphic enzyme loci (of a total of 22 loci sampled) in 15 populations of the neotropical giant toad, Bufo marinus, introduced to Hawaii and Australia in the 1930s. The history of establishment of the ten populations is described and used as a framework for the analysis of allele frequency variances. The variances are used to determine the effective sizes of the populations. The estimates obtained (390 and 346) are reasonably precise, homogeneous between localities and much smaller than estimates of neighborhood size obtained previously using ecological methods. This discrepancy is discussed, and it is concluded that the estimates obtained here using genetic methods are the more reliable.
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Ruzzante, Daniel E. "A comparison of several measures of genetic distance and population structure with microsatellite data: bias and sampling variance." Canadian Journal of Fisheries and Aquatic Sciences 55, no. 1 (January 1, 1998): 1–14. http://dx.doi.org/10.1139/f97-203.
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Because of their rapid mutation rate and resulting large number of alleles, microsatellite DNA are well suited to examine the genetic or demographic structure of fish populations. However, the large number of alleles imply that large sample sizes are required for accurate reflection of genotypic frequencies. Estimates of genetic distance are often biased at small sample sizes, and biases and sampling variances can be affected by the number of, and distances between, alleles. Using data from a large collection of larval cod (Gadus morhua) from a single area, I examined the effect of sample size on seven genetic distance and two structure metrics. Pairs of samples (equal or unequal) of various sizes were drawn at random from a pool of 856 individuals scored for six microsatellite loci. ( delta µ)2, DSW, RST, and FST were the best performers in terms of bias and variance. Sample sizes of 50 <= N <= 100 individuals were generally necessary for precise estimation of genetic distances and this value depended on number of loci, number of alleles, and range in allele size. ( delta µ)2 and DSW were biased at small sample sizes.
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Wensch-Dorendorf, M., N. Mielenz, E. Groeneveld, M. Kovac, and L. Schüler. "Varianzkomponentenschätzung unter Berücksichtigung von Dominanz an simulierten Reinzuchtlinien." Archives Animal Breeding 47, no. 4 (October 10, 2004): 387–95. http://dx.doi.org/10.5194/aab-47-387-2004.
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Abstract. Title of the paper: Estimation of variance components under dominance with simulated purebred lines A stochastic simulation based on a gene model was used to investigate the estimation of variance with dominance and additive animal models. For a heritability in broad sense of 0.5 three ratios of dominance variance (5, 10 and 25%) on the phenotypic variance were investigated under different degrees of dominance. No additionally biased estimations of the variance components as consequence of different dominance degrees were found. By using the dominance model for random mating as well as for selection the differences between true parameters and estimation values were small for all dominance degrees and ratios of dominance variance. Small, but significantly, differences can be explained by the change of the allele frequencies over the generations due to the influence of selection. By using the additive animal model, that ignores the dominance relationship, for high ratios of the dominance variance (25% or greater) important biased estimations of the variances were observed. For dominance ratios of 5% no significantly overestimation of the additive variances with the reduced model were found under selection and random mating.
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Jakse, Jernej, Zlatko Satovic, and Branka Javornik. "Microsatellite variability among wild and cultivated hops (Humulus lupulus L.)." Genome 47, no. 5 (October 1, 2004): 889–99. http://dx.doi.org/10.1139/g04-054.
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Hop (Humulus lupulus L.) is a dioecious perennial plant native to the northern hemisphere cultivated for its use in the brewing industry. To investigate the genetic diversity present in wild hop accessions in comparison with cultivated hops, microsatellite marker variation was assessed at four loci in 124 accessions of wild (from Europe, Asia and from North America) and cultivated (varieties and breeding lines) hops. A total of 63 alleles were identified, with an average of 15.7 alleles per locus and an average PIC of 0.64 over four loci. The average number of alleles per locus in groups of accessions ranged from 5.75 to 8.30, with the highest number detected in groups of wild hops either of European (EU) or North American (NA) origin. Accessions from NA revealed the highest number of unique alleles indicating the high diversity present in this gene pool. Cluster analysis based on the DD or Dsw distance matrix divided accessions into 10 different clusters, which reflect the relationship among geographically diverse wild accessions and hop cultivars. The highest genetic differences were found between NA wild accessions, forming one distant cluster, and all the other accessions. The differentiation between European wild and cultivated accessions was revealed by PCoA based on the DD distance matrix and by AMOVA results. Cultivated hops differ significantly from wild ones, although most of the variability was found within groups. The molecular variances within groups of cultivated and wild hops were homogeneous, suggesting that a similar level of molecular variability is found in both groups of accessions. The analysis of allele polymorphism and of allele sequences showed that hop germplasm can be differentiated to NA and EU geographic types according to the differences of allele sizes at three loci or by the specific microsatellite repeat type at one locus. The analysis also indicates the different evolutionary dynamics and complex mutations of microsatellite sequences within loci that can be followed in the two biogeographically separated germplasms.Key words: Humulus lupulus L., genetic diversity, germplasm, microsatellites, allele sequence variation.
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Lynch, Michael, and Wei-Chin Ho. "The Limits to Estimating Population-Genetic Parameters with Temporal Data." Genome Biology and Evolution 12, no. 4 (March 29, 2020): 443–55. http://dx.doi.org/10.1093/gbe/evaa056.
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Abstract The ability to obtain genome-wide sequences of very large numbers of individuals from natural populations raises questions about optimal sampling designs and the limits to extracting information on key population-genetic parameters from temporal-survey data. Methods are introduced for evaluating whether observed temporal fluctuations in allele frequencies are consistent with the hypothesis of random genetic drift, and expressions for the expected sampling variances for the relevant statistics are given in terms of sample sizes and numbers. Estimation methods and aspects of statistical reliability are also presented for the mean and temporal variance of selection coefficients. For nucleotide sites that pass the test of neutrality, the current effective population size can be estimated by a method of moments, and expressions for its sampling variance provide insight into the degree to which such methodology can yield meaningful results under alternative sampling schemes. Finally, some caveats are raised regarding the use of the temporal covariance of allele-frequency change to infer selection. Taken together, these results provide a statistical view of the limits to population-genetic inference in even the simplest case of a closed population.
Dissertations / Theses on the topic "Allele variances"
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Hummel, Matthew Aaron. "Dapsone activation of CYP2C9 allelic variants." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=2767.
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Thesis (M.S.)--West Virginia University, 2003.Title from document title page. Document formatted into pages; contains vi, 42 p. : ill. Includes abstract. Includes bibliographical references (p. 35-42).
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Milani, Lili. "Gene Expression in Cancer Cells : Detection of Splice Variants, Allele-specific Expression and DNA Methylation." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-99067.
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Makambwa, Edson. "The role of warfarin pharmacogenomics on the time it takes to reach stable therapeutic International Normalized Ratio (INR) and on warfarin dose required to maintain stable therapeutic INR in Black African and Mixed Ancestry South Africans: a focus on CYP2C9 and VKORC1." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31178.
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Warfarin, the most commonly prescribed anticoagulant, is principally metabolized by cytochrome P450 2C9 which functions by inhibiting the Vitamin K epoxide reductase. Genes CYP2C9 and VKORC1 code for these two proteins, respectively. CYP2C9 and VKORC1 exhibit genetic polymorphisms that have been shown to affect warfarin response and favorably facilitate warfarin dosing and improve clinical outcomes. However, none of these studies have involved populations from sub-Saharan Africa where the potential benefit of optimal dosing and reduced complications is greatest. Therefore, the thesis describes a study designed to investigate the role of genetic variations in CYP2C9 and VKORC1 on the time taken to reach a stable therapeutic international normalized ratio (INR) and warfarin dose required to maintain a therapeutic INR. This was a cross-sectional study of patients on warfarin to determine the relationship between genetic polymorphism in CYP2C9 and VKORC1 amongst black and mixed ancestry South Africans and clinical surrogates of warfarin metabolism. Medical records were accessed to determine time to INR and warfarin doses. DNA was extracted from blood samples, and genotyping for polymorphism in CYP2C9 (*2,*3,*8,*11) and VKORC1 (1173C>T, 1639G>A, 3730G>A) was accomplished by PCR-RFLP, Sanger sequencing and iPlex Mass Sequencing. Our results show that the genetic profile of CYP2C9 and VKORC1 differs between Black Africans (BA) and their Mixed Ancestry (MA) counterparts. VKORC1-1639AA genotype was observed at frequencies of 0.11 and 0.01 in the MA and BA, respectively. Time to stable INR was not influenced by CYP2C9 and VKORC1. Furthermore, compared to known genetic polymorphisms in these genes from population out of Africa, both qualitative and quantitative differences were observed. Finally, we found that VKORC1 genetic variation significantly affected the doses of warfarin in MA but had no effect in BA. These results suggest that further research in this area is warranted, and that it will be important to include populations from sub-Saharan Africa in future if the potential to develop personalized algorithms which integrate pharmacogenomics to assist with effective warfarin dosing and prevention of warfarin related complications is to be realized.
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Cid, Nuria Alonso Lopez. "AVALIAÇÃO DE POLIMORFISMOS DA CYP3A5 EM INDIVÍDUOS DA REGIÃO CENTRO-OESTE DO BRASIL." Pontifícia Universidade Católica de Goiás, 2016. http://localhost:8080/tede/handle/tede/2410.
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Previous issue date: 2016-04-14The advances in Anesthesiology took place at the same time as the development of drugs that ensured greater control over pain, patient comfort, and safety during surgical anesthetic procedures. Pharmacogenetics is the science that enables enhanced healthcare, by understanding the genetic variations that may affect the different responses to treatments. CYP3A are the most important enzymes involved in the metabolism of drugs prescribed in clinical practice, showing extensive genetic variability in their expression. CYP3A5 presents the highest number of functional variants, with significant differences in the frequencies observed among different population groups around the world and in Brazil. This study aimed and at assessing the frequency of CYP3A5*3 and CYP3A5*6 genotypic and allelic variants and to estimate the metabolizing profile according to these variants, as well as any potential implications on adverse events with drugs used in anesthesia. The sample used for this study included 166 subjects users of the Laboratório da Área de Saúde da PUCGoiás (PUC Healthcare Laboratory city of Goiás). They were all born in the Brazilian Midwest, over 18 years of age, and from both genders. The blood samples were obtained from each individual and genotyped for CYP3A5*3, A>G (rs 776746) and CYP3A5*6, G>A (rs 10264272) by real time Polymerase Chain Reaction using TaqMan assays. Data analysis of the allelic frequency was conducted by calculating the percentage for the established groups, according to color or race, compared to the total sample. In individuals from the Brazilian Midwest, assessed in this study, the frequency of the allelic variant CYP3A5*3 was 40% and 2% for CYP3A5*6. The frequency observed for the CYP3A5*3 allelic variant in subjects from the Midwest was lower than that from other Brazilian studies and also lower than the frequencies observed in Europeans and Asians, however, they were similar to the frequency seen in populations from East and West Africa. The frequency of the CYP3A5*6 allelic variant, in this study, was higher than that found in European studies and similar of the subjects in the North of Africa. Based on the results, one may infer that 72% would be poor metabolizers. The higher frequency of the poor metabolizer profile shows that there is potential for a greater occurrence of adverse events when using drugs metabolized by CYP3A5 in this population from the Brazilian Midwest.
O progresso da Anestesiologia junto com o desenvolvimento de drogas garantiram maior controle da dor, conforto ao paciente e segurança durante o ato anestésicocirúrgico. A Farmacogenética é uma ciência que permite a melhora da assistência à saúde, por meio do conhecimento das variações genéticas que podem estar envolvidas com as diferenças na resposta terapêutica. As CYP3A são as enzimas mais importantes envolvidas com o metabolismo de drogas prescritas na prática clínica, apresentando grande variabilidade genética na sua expressão. A CYP3A5 é a forma que apresenta mais variantes funcionais e com diferenças expressivas nas frequências observadas em diferentes grupos populacionais do mundo. Este estudo teve como objetivo avaliar a frequência das variantes genotípicas e alélicas do CYP3A5*3 e CYP3A5*6 e inferir sobre o perfil metabolizador dos indivíduos em função destas variantes em relação a drogas usadas em anestesia. O grupo avaliado incluiu 166 indivíduos usuários do Laboratório da Área de Saúde da PUCGoiás, nascidos na região Centro-Oeste do Brasil, maiores de 18 anos e de ambos os sexos. As amostras de sangue foram obtidas de cada indivíduo e genotipados para CYP3A5*3, A>G (rs 776746) and CYP3A5*6, G>A (rs 10264272) por Reação em Cadeia de Polimerase usando sondas TaqMan. A análise dos dados das frequências alélicas foi realizada através do cálculo das porcentagens para os grupos estabelecidos, segundo a cor ou raça, em relação a amostra total. Nos indivíduos da região Centro-Oeste do Brasil avaliados neste estudo, a frequência da variante alélica CYP3A5*3 foi de 40% e da CYP3A5*6 foi de 2%. A frequência observada para a variante alélica CYP3A5*3 em indivíduos da região Centro-Oeste foi menor que a de outros estudos brasileiros e também menor que as frequências verificadas em europeus e asiáticos, porém similar à observada na população do leste e oeste da África. A frequência da variante alélica CYP3A5*6, neste estudo, foi maior que a encontrada em estudos europeus e com valores mais próximos daqueles observados no norte da África. Com base nos resultados obtidos da amostra pode-se inferir que 72% dos indivíduos seriam fracos metabolizadores. A maior frequência do perfil de fraco metabolizador mostra que existe potencial de maior ocorrência de eventos adversos no uso de fármacos metabolizados pela CYP3A5 nesta população da região Centro-Oeste do Brasil.
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Yang, Su jeong. "Biochemical and biophysical characterisation of allelic variants of ovine prion protein." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611255.
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Walton, Esther, Daniel Geisler, Johannes Hass, Jingyu Liu, Jessica Turner, Anastasia Yendiki, Michael N. Smolka, et al. "The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-132122.
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The neural mechanisms underlying genetic risk for schizophrenia, a highly heritable psychiatric condition, are still under investigation. New schizophrenia risk genes discovered through genome-wide association studies (GWAS), such as neurogranin (NRGN), can be used to identify these mechanisms. In this study we examined the association of two common NRGN risk single nucleotide polymorphisms (SNPs) with functional and structural brain-based intermediate phenotypes for schizophrenia. We obtained structural, functional MRI and genotype data of 92 schizophrenia patients and 114 healthy volunteers from the multisite Mind Clinical Imaging Consortium study. Two schizophrenia-associated NRGN SNPs (rs12807809 and rs12541) were tested for association with working memory-elicited dorsolateral prefrontal cortex (DLPFC) activity and surface-wide cortical thickness. NRGN rs12541 risk allele homozygotes (TT) displayed increased working memory-related activity in several brain regions, including the left DLPFC, left insula, left somatosensory cortex and the cingulate cortex, when compared to non-risk allele carriers. NRGN rs12807809 non-risk allele (C) carriers showed reduced cortical gray matter thickness compared to risk allele homozygotes (TT) in an area comprising the right pericalcarine gyrus, the right cuneus, and the right lingual gyrus. Our study highlights the effects of schizophrenia risk variants in the NRGN gene on functional and structural brain-based intermediate phenotypes for schizophrenia. These results support recent GWAS findings and further implicate NRGN in the pathophysiology of schizophrenia by suggesting that genetic NRGN risk variants contribute to subtle changes in neural functioning and anatomy that can be quantified with neuroimaging methods.
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Jin, Huilin. "Mechanisms of osteoporosis associated with common allelic variants of the COL1A1 gene." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/29182.
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Three single nucleotide polymorphisms (SNP) have been identified in the 5’ flank of the COLIA1 gene (-1997G/T; -1663IndelT and +1245G/T) which have been associated with osteoporosis in various populations. The individual polymorphisms were all associated with BMD, but the haplotypes defined by all three SNP showed a stronger association with BMD, biomechanical strength of bone and hip fracture. Two haplotypes increased in frequency with age suggesting an effect on survival. However these haplotypes were particularly enriched in hip fracture patients. Biomechanical testing showed that all three SNPs were strongly associated with reduced bone strength, independently of BMD. Gel shift assays showed that the region surrounding the -1663insdeIT polymorphism recognised the nuclear binding proteins NMP4 and Osterix and the -1663deIT allele had greater binding affinity than -1663insT allele. the region surrounding the -1997 G/T polymorphism also recognised DNA binding proteins but the polymorphism did not have affect DNA protein binding significantly. Reporter assays showed significant differences between the ability of different haplotypes to drive gene expression and constructs containing haplotype (G-delT-T) had the highest transcriptional activity (p<0.001). Transgenic constructs containing different 5’ COL1A1 haplotypes were completed and transformed into mouse embryonic stem cells by electroporation in an attempt to generate a disease model of osteoporosis associated with common variants in the COLIA1 gene. The studies suggest that haplotypes, rather than individual polymorphisms in the 5’ flank of COL1A1 predispose to osteoporosis, by affecting DNA protein interactions and gene expression.
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Albers, Patrick K. "Rare and low-frequency variants and predisposition to complex disease." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:2d569297-5d2a-49c8-a1ca-32a978aec49d.
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Advances in high-throughput genomic technologies have facilitated the collection of DNA information for thousands of individuals, providing unprecedented opportunities to explore the genetic architecture of complex disease. One important finding has been that the majority of variants in the human genome are low in frequency or rare. It has been hypothesised that recent explosive growth of the human population afforded unexpectedly large amounts of rare variants with potentially deleterious effects, suggesting that rare variants may play a role in disease predisposition. But, importantly, rare variants embody a source of information through which we may learn more about our recent evolutionary history. In this thesis, I developed several statistical and computational methods to address problems associated with the analysis of rare variants and, foremost, to leverage the genealogical information they encode. First, one constraint in genome-wide association studies is that lower-frequency variants are not well captured by genotyping methods, but instead are predicted through imputation from a reference dataset. I developed the meta-imputation method to improve imputation accuracy by integrating genotype data from multiple, independent reference panels, which outperformed imputations from separate references in almost all comparisons (mean correlation with masked genotypes r2>0.9). I further demonstrated in simulated case-control studies that meta-imputation increased the statistical power to identify low-frequency variants of intermediate or high penetrance by 2.2-3.6%. Second, rare variants are likely to have originated recently through mutation and thereby sit on relatively long haplotype regions identical by descent (IBD). I developed a method that exploits rare variants as identifiers for shared haplotype segments around which the breakpoints of recombination are detected using non-probabilistic approaches. In coalescent simulations, I show that such breakpoints can be inferred with high accuracy (r2>0.99) around rare variants at frequencies <0.05%, using either haplotype or genotype data. Third, I show that technical error poses a major problem for the analysis of whole-genome sequencing or genotyping data, particularly for alleles below 0.05% frequency (false positive rate, FPR=0.1). I therefore propose a novel approach to infer IBD segments using a Hidden Markov Model (HMM) which operates on genotype data alone. I incorporated an empirical error model constructed from error rates I estimated in publicly available sequencing and genotyping datasets. The HMM was robust in presence of error in simulated data (r2>0.98) while nonprobabilistic methods failed (r2<0.02). Lastly, the age of an allele (the time since its creation through mutation) may provide clues about demographic processes that resulted in its observed frequency. I present a novel method to estimate (rare) allele age based on the inferred shared haplotype structure of the sample. The method operates in a Bayesian framework to infer pairwise coalescent times from which the age is estimated using a composite posterior approach. I show in simulated data that coalescent time can be inferred with high accuracy (rank correlation >0.91) which resulted in a likewise high accuracy for estimated age (>0.94). When applied to data from the 1000 Genomes Project, I show that estimated age distributions were overall conform with frequency-dependent expectations under neutrality, but where patterns of low frequency and old age may hint at signatures of selection at certain sites. Thus, this method may prove useful in the analysis of large cohorts when linked to biomedical phenotype data.
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Gréard, Camille. "La détection des variants alléliques comme voie d'amélioration génétique des plantes fourragères : exemple de la luzerne." Thesis, Poitiers, 2019. http://www.theses.fr/2019POIT2261.
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L’amélioration génétique de la luzerne (Medicago sativa), une légumineuse fourragère autotétraploïde, pourrait bénéficier de l’allele mining. Cette méthode consiste à rechercher, dans la diversité naturelle, des allèles ayant potentiellement un effet sur le phénotype. Pour évaluer l’intérêt de cette stratégie qui exploite la diversité naturelle, cinq gènes impliqués dans des caractères sélectionnés ont été retenus : CAD1 et CCoaOMT (digestibilité), CONSTANS-like (rendement fourrager), NHX1 (tolérance à la salinité) et WXP1 (tolérance à la sécheresse). La diversité de ces gènes a été étudiée en séquençant 387 génotypes cultivés et 20 génotypes sauvages. L’analyse des données confirme la présence d’un goulot d’étranglement durant la domestication et la sélection de la luzerne. CONSTANS-like et WXP1 révèlent de nombreux variants alors que CAD1, CCoaOMT et NHX1 sont très peu variables. Des variants ayant un effet potentiel sur le phénotype ont été identifiés dans les zones de la séquence protéique qui sont conservées au sein des Faboideae. L’impact sur le phénotype de deux variants du gène CONSTANS-like a été étudié : Constans-634, à l’origine d’un codon stop prématuré et Constans-4111, situé dans une région conservée du gène. Pour cela des croisements ont été réalisés afin d’obtenir une descendance avec toutes les doses possibles (AAAA, AAAB, AABB, ABBB and BBBB) pour chaque mutation étudiée. Des marqueurs KASPar ont été développés afin de déterminer les doses de mutations chez les descendants. Aucun génotype homozygote muté pour Constans-634 n’a été détecté parmi les 1505 descendants. Ce variant a induit une floraison plus précoce de trois jours pour les génotypes portant trois doses d’allèle muté. Le variant Constans-4111 a induit un effet additif sur la hauteur de tige. Les génotypes homozygotes de type sauvage étaient en moyenne 11,8 cm plus petits que les génotypes homozygotes portant trois ou quatre doses du variant. L’intégration de la stratégie allele mining dans les schémas de sélection des espèces végétales autotétraploïdes hétérozygotes a été discutéeLucerne (Medicago sativa) is an autotetraploid forage legume, whose breeding could beneficiate from allele mining. This strategy is based on the natural diversity and consists in seeking alleles with a potential effect on the phenotype. The interest of this approach was evaluated by studying five genes of agronomic interest: CAD1 and CCoaOMT (digestibility), CONSTANS-like (forage yield), NHX1 (salt tolerance) and WXP1 (drought tolerance). The diversity of these five genes was evaluated by sequencing 387 genotypes of cultivated accessions and 20 genotypes of wild accessions. The results confirmed a bottleneck during lucerne domestication and selection. CONSTANS-like and WXP1 were very variable whereas CAD1, CCoaOMT and NHX1 contained very few variants. Variants with a potential strong impact on the phenotype were identified in conserved parts of protein sequence within the Faboideae. The impact on phenotype was studied for two mutations of the CONSTANS-like gene: constans-634, causing a premature stop codon and constans-4111, located in a conserved region of the gene. Genotypes carrying one to three doses of the mutations (AAAB, AABB and ABBB) were polycrossed in order to obtain offsprings with every allele combination (AAAA, AAAB, AABB, ABBB and BBBB). KASPar markers were developed to determine the mutation doses in offspring progeny. No homozygous genotype was found for constans-634 in the 1505 offspring progeny. This mutation induced a premature flowering of three days for the genotypes carrying three doses of the mutation. The mutation constans-4111 induced an additive effect on stem height and the homozygous genotypes without the variant where on average 11.8 cm shorter than homozygous genotypes carrying three or four doses of the variant. The application of allele mining strategy in plant schemes of heterozygous autotetraploid species was discussed
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Johnson, Andrew Danner. "Search for functional alleles in the human genome with focus on cardiovascular disease candidate genes." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187018497.
Full textBooks on the topic "Allele variances"
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Walsh, Bruce, and Michael Lynch. Short-term Changes in the Variance: 1. Changes in the Additive Variance. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198830870.003.0016.
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Selection changes the additive-genetic variance (and hence the response in the mean) by both changing allele frequencies and by generating correlations among alleles at different loci (linkage disequilibrium). Such selection-induced correlations can be generated even between unlinked loci, and (generally) are negative, such that alleles increasing trait values tend to become increasingly negative correlated under direction or stabilizing selection, and positively correlated under disruptive selection. Such changes in the additive-genetic variance from disequilibrium is called the Bulmer effects. For a large number of loci, the amount of change can be predicted from the Bulmer equation, the analog of the breeder's equation, but now for the change in the variance. Upon cessation of selection, any disequilibrium decays away, and the variances revert back to their additive-genic variances (the additive variance in the absence of disequilibrium). Assortative mating also generates such disequilibrium.
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Walsh, Bruce, and Michael Lynch. Analysis of Short-term Selection Experiments: 2. Mixed-model and Bayesian Approaches. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198830870.003.0019.
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When the full pedigree of individuals whose values (records) were used in the selection decisions during an experiment (or breeding program) is known, LS analysis can be replaced by mixed models and their Bayesian extensions. In this setting, REML can be used to estimate genetic variances and BLUP can be used to estimate the mean breeding value in any given generation. The latter allows for genetic trends to be separated from environmental trends without the need for a control population. Under the infinitesimal model setting (wherein selection-induced allele-frequency changes are small during the course of the experiment), the use of the relationship matrix in a BLUP analysis accounts for drift, nonrandom mating, and linkage disequilibrium.
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Apolipoprotein E (ApoE) allelic variants: Involvement in type 2 dibetes. Ottawa: National Library of Canada, 2003.
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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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Walsh, Bruce, and Michael Lynch. The Infinitesimal Model and Its Extensions. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198830870.003.0024.
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One standard approximation in quantitative genetics is the infinitesimal model, which assumes a large number of loci, each of small effect. In such a setting, the distribution of breeding values in unselected descendants is roughly multivariate normal and most of the (short-term) change in the additive variance under selection is through Bulmer effects (the generation of linkage disequilibrium) rather than by allele-frequency change. A variety of different infinitesimal models are found in the literature, and this chapter examines these different versions and the connections between them. It also examines the theory for moving beyond the infinitesimal approximation. Finally, this chapter shows that the much-debated worry over “missing heritability” simply follows under the infinitesimal setting.
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Cazeneuve, Cécile, and Alexandra Durr. Genetic and Molecular Studies. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199929146.003.0006.
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Huntington’s disease (HD) is a rare inherited neurologic disorder due to a single mutational mechanism in a large gene (HTT). The mutation is an abnormal CAG repeat expansion, which is translated to a polyglutamine stretch in the huntingtin protein. The growing field of repeat expansion disorders benefits greatly from the lessons learned from the role of the CAG repeat expansion in HD and its resulting phenotype–genotype correlations. The molecular diagnosis can be difficult, and there are some pitfalls for accurate sizing of the CAG repeat, especially in juvenile HD and for intermediate alleles. Correlation between CAG length and age of onset accounts for up to 72% of the variance in different populations, but the search for genes modifying age of onset or progression of HD is still ongoing.
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Hegel, Georg Wilhelm Friedrich. Vorlesungen über die Philosophie der Religion und Vorlesungen über die Beweise vom Dasein Gottes II. Felix Meiner Verlag, 2021. http://dx.doi.org/10.28937/978-3-7873-3735-4.
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Dieser Band umfasst zum einen den Text von Hegels Kolleg zur Philosophie der Religion des Jahres 1827, in dem Hegel gegenüber dem vorhergehenden Kolleg von 1824 tiefgreifende Änderungen vorgenommen hat, und ferner die allein überlieferten Auszüge aus einer Nachschrift des Religionsphilosophie-Kollegs von 1831. Ergänzt werden diese beiden Textgruppen durch Sondergut der ›Freundesvereinsausgabe‹, das in den heute vorhandenen Quellen nicht mehr enthalten ist. Zum anderen enthält der Band eine hier erstmals edierte vollständige Nachschrift zu Hegels Kolleg über die Beweise vom Dasein Gottes aus dem Sommersemester 1829, mit Varianten einer bereits bekannten Nachschrift desselben Kollegs.
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Barr, Christina S. Gene-by-Environment Interactions in Primates. Edited by Turhan Canli. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199753888.013.006.
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Because of their complex social structures, behaviors, and genetic similarities to humans, nonhuman primates are useful for studying how genetic factors influence alcohol consumption. The neurobiological systems that influence addiction vulnerability may do so by acting on alcohol response, reward pathways, behavioral dyscontrol, and vulnerability to stress and anxiety. Rhesus macaques show individual differences in alcohol response and temperament, and such differences are influenced by genetic variants that are similar functionally to those present in humans. Genes in which variation moderates these phenotypes provide opportunities for modeling how genetic and environmental factors (i.e., stress exposure, individual’s sex, or alcohol response) interact to influence alcohol consumption. Studies in primates may also reveal selective factors that have driven maintenance or fixation of alleles that increase risk for alcohol use disorders in modern humans.
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Collin, Peter, Gert Bender, Stefan Ruppert, Margrit Seckelmann, and Michael Stolleis, eds. Selbstregulierung im 19. Jahrhundert – zwischen Autonomie und Steuerungsansprüchen. Klostermann, 2013. http://dx.doi.org/10.5771/9783465141228.
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Regulierte Selbstregulierung ist mittlerweile zu einem Schlüsselbegriff der rechts- und politikwissenschaftlichen Diskussion geworden. Man findet sie heute in vielerlei Gestalt. Gemeinsam ist allen Varianten eine Kombination aus einem staatlichen Steuerungsanteil und einem Eigenregulierungsanteil der gesellschaftlichen Akteure. Die historischen Dimensionen Regulierter Selbstregulierung, ihrer rechtlichen Ausformungen, aber auch ihrer ökonomischen, kulturellen und sozialpolitischen Kontexte herauszuarbeiten, ist die Aufgabe des am Max-Planck-Institut für europäische Rechtsgeschichte angesiedelten Projekts "Regulierte Selbstregulierung in historischer Perspektive". Dieser Band dokumentiert die Ergebnisse einer Tagung, die vom 9. bis zum 11. Juli 2009 in Bad Homburg stattfand.
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Johansson, Ann-Sofie. Exploring the Functional Plasticity of Human Glutathione Transferases: Allelic Variants, Novel Isoenzyme & Enzyme Redesign (Comprehensive Summaries of ... the Faculty of Science and Technology, 695). Uppsala Universitet, 2002.
Find full textBook chapters on the topic "Allele variances"
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Lefferts, Juliet W., Vera Boersma, Marne C. Hagemeijer, Karima Hajo, Jeffrey M. Beekman, and Erik Splinter. "Targeted Locus Amplification and Haplotyping." In Methods in Molecular Biology, 31–48. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2819-5_2.
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AbstractTargeted locus amplification (TLA) allows for the detection of all genetic variation (including structural variation) in a genomic region of interest. As TLA is based on proximity ligation, variants can be linked to each other, thereby enabling allelic phasing and the generation of haplotypes. This allows for the study of genetic variants in an allele-specific manner. Here, we provide a step-by-step protocol for TLA sample preparation and a complete bioinformatics pipeline for the allelic phasing of TLA data. Additionally, to illustrate the protocol, we show the ability of TLA to re-sequence and haplotype the complete cystic fibrosis transmembrane (CFTR) gene (> 200 kb in size) from patient-derived intestinal organoids.
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Hakomori, Sen-Itiroh. "Histoblood Group A Variants, O Variants, and Their Alleles." In Handbook of Glycosyltransferases and Related Genes, 189–96. Tokyo: Springer Japan, 2002. http://dx.doi.org/10.1007/978-4-431-67877-9_25.
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Abraham, Jashan P., Dominic J. Barker, James Robinson, Giuseppe Maccari, and Steven G. E. Marsh. "The IPD Databases: Cataloguing and Understanding Allele Variants." In Methods in Molecular Biology, 31–48. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8546-3_3.
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Hakomori, Sen-itiroh, and Monica Palcic. "Histo-Blood Group A Variants, O Variants, and Their Alleles." In Handbook of Glycosyltransferases and Related Genes, 479–93. Tokyo: Springer Japan, 2014. http://dx.doi.org/10.1007/978-4-431-54240-7_159.
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Belt, Peter B. G. M., Alex Bossers, Bram E. C. Schreuder, and Mari A. Smits. "PrP Allelic Variants Associated with Natural Scrapie." In Bovine Spongiform Encephalopathy, 294–305. New York, NY: Springer New York, 1996. http://dx.doi.org/10.1007/978-1-4612-2406-8_21.
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Serrano, Ezequiel, Pablo G. Sanz, and Francisco J. Barrantes. "The Impact of Apolipoprotein E Allelic Variants on Alzheimer’s Disease." In Psychiatry and Neuroscience Update, 397–418. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-61721-9_29.
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Geng, Yu, Zhongmeng Zhao, Jing Xu, Ruoyu Liu, Yi Huang, Xuanping Zhang, Xiao Xiao, Maomao, and Jiayin Wang. "Identifying Heterogeneity Patterns of Allelic Imbalance on Germline Variants to Infer Clonal Architecture." In Intelligent Computing Theories and Application, 286–97. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-63312-1_26.
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Brammli-Greenberg, Shuli, Inon Buda, and Yoram Weiss. "Stationäre Versorgung und Patientensteuerung während der Covid-19-Pandemie in Israel." In Krankenhaus-Report 2022, 235–47. Berlin, Heidelberg: Springer Berlin Heidelberg, 2022. http://dx.doi.org/10.1007/978-3-662-64685-4_13.
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Zusammenfassung Zusammenfassung Wie in vielen anderen Länder kam es Ende Februar 2020 auch in Israel zu den ersten flächendeckenden Covid-19-Ausbrüchen. Die Pandemie, die inzwischen seit mehr als 18 Monaten andauert, wies mehrere aufeinanderfolgende Wellen auf, die meist mit dem Auftreten neuer Varianten des SARS-CoV-2-Virus zusammenhingen. Die Verantwortlichen in allen Bereichen des Gesundheitswesens mussten sich an die Situation anpassen, mit großen Unsicherheiten umgehen und tagtäglich Lösungen finden, um trotz Personalknappheit und mangelnder Schutzausrüstung die gesamte Bevölkerung – mit oder ohne Covid-19 – zu versorgen. Dieser Beitrag gibt einen Überblick über die stationäre Versorgung und die Patientensteuerung in Israel während der Covid-19-Pandemie. Angesichts der Erkenntnis, dass das Krankenhausmanagement in der Lage sein muss, auf ständige Veränderungen rasch zu reagieren und sich an die weiterhin vorliegenden pandemischen Bedingungen anzupassen, um allen Patientinnen und Patienten die bestmögliche medizinische Versorgung zu bieten, schlagen die Autoren einen vierstufigen Aktionsplan vor, den das Krankenhaussystem in Erwägung ziehen sollte, um der anhaltenden Covid-19-Pandemie besser begegnen zu können.
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Luu, Alice, Brian C. Foster, Kristina L. McIntyre, Teresa W. Tam, and John T. Arnason. "Pharmacogenetics in Potential Herb–Drug Interactions: Effects of Ginseng on CYP3A4 and CYP2C9 Allelic Variants." In The Biological Activity of Phytochemicals, 59–65. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-7299-6_5.
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Krüger, Timmo. "Mehr Fortschritt wagen? Eine essayistische Kritik der Wette auf grünes Wachstum." In Soziale Bewegung und Protest, 63–80. Bielefeld, Germany: transcript Verlag, 2022. http://dx.doi.org/10.14361/9783839463000-004.
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Timmo Krüger interpretiert in seinem Beitrag die regierungspolitische Hoffnung auf grünes Wachstum als klimapolitische Variante einer Faustischen Wette. Er arbeitet heraus, weshalb der Faustische Weg des Kolonialismus und der Naturbeherrschung in der Dichtung gescheitert ist und auch in der Realität misslingen wird. Alternativ schlägt Timmo Krüger vor, den Zwang zum Fortschritt hinter uns zu lassen, unserer Abhängigkeit von Natur gewahr zu werden und uns auf Regelungen der kollektiven Selbstbeschränkung zu einigen, die Gleichheit und Freiheit für alle bieten. Er plädiert für die Wiederaneignung einer solidarischen Kultur der Selbstbeschränkung, in der Praktiken des Teilens und der demokratischen Selbstorganisation gelebt werden.
Conference papers on the topic "Allele variances"
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Makey, T. V., and P. M. Marozik. "GENETIC FACTORS OF PREPOSITION TO BONE FRACTURES IN ATHLETES." In SAKHAROV READINGS 2021: ENVIRONMENTAL PROBLEMS OF THE XXI CENTURY. International Sakharov Environmental Institute, 2021. http://dx.doi.org/10.46646/sakh-2021-1-287-290.
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A retrospective study was carried out, which included professional athletes. The athletes were divided into two groups, depending on the presence of bone fractures in the anamnesis. DNA isolated from the buccal epithelium was used as a biological material. Two informative genetic markers were identified that statistically increase the risk of stress fractures in the study group. The most significant differences between the studied groups in the distribution of genotype and allele frequencies were found for the rs7975232 variants of the VDR gene and rs42517 of the COL1A2 gene. The results indicate the important role of these loci in the pathogenesis of fractures. Identification of unfavorable variants of allelic combinations makes it possible to assess the individual risk of bone fractures.
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"AD ASTRA: the database of Allelic Dosage-corrected Allele-Specific TRAnscription factor binding suggests causal regulatory sequence variants of pathologies." In Bioinformatics of Genome Regulation and Structure/ Systems Biology. institute of cytology and genetics siberian branch of the russian academy of science, Novosibirsk State University, 2020. http://dx.doi.org/10.18699/bgrs/sb-2020-001.
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Elrayess, Mohamed, Fatima Al-Khelaifi, Noha Yousri, and Omar Al-Bagha. "Genome-Wide Association study Identifies a Novel Association Between a Cardiovascular Gene Polymorphism and Superior Athletic Performance." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0111.
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Research into the genetic predisposition to superior athletic performance has been a hindered by the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high (n=662) and low/moderate (n=134) aerobic component. Validation of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (MYBPC3; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (P=1.43E-08, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO2max than carriers of the AA+AG (P = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82x10-05) including the testosterone precursor androstenediol (3beta, 17beta) disulfate. Conclusion: This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.
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Smatti, Maria K., Yasser Al-Sarraj, Omar Albagha, and Hadi M. Yassine. "Host Genetic Variants Potentially Associated with SARS-Cov-2: A Multi-Population Analysis." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0298.
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Background: Clinical outcomes of Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) showed enormous inter-individual and interpopulation differences, possibly due to host genetics differences. Earlier studies identified single nucleotide polymorphisms (SNPs) associated with SARS-CoV-1 in Eastern Asian (EAS) populations. In this report, we aimed at exploring the frequency of a set of genetic polymorphisms that could affect SARS-CoV-2 susceptibility or severity, including those that were previously associated with SARS-CoV-1. Methods: We extracted the list of SNPs that could potentially modulate SARS-CoV-2 from the genome wide association studies (GWAS) on SARS-CoV-1 and other viruses. We also collected the expression data of these SNPs from the expression quantitative trait loci (eQTLs) databases. Sequences from Qatar Genome Programme (QGP, n=6,054) and 1000Genome project were used to calculate and compare allelic frequencies (AF). Results: A total of 74 SNPs, located in 10 genes: ICAM3, IFN-γ, CCL2, CCL5, AHSG, MBL, Furin, TMPRSS2, IL4, and CD209 promoter, were identified. Analysis of Qatari genomes revealed significantly lower AF of risk variants linked to SARS-CoV-1 severity (CCL2, MBL, CCL5, AHSG, and IL4) compared to that of 1000Genome and/or the EAS population (up to 25-fold change). Conversely, SNPs in TMPRSS2, IFN-γ, ICAM3, and Furin were more common among Qataris (average 2-fold change). Inter-population analysis showed that the distribution of risk alleles among Europeans differs substantially from Africans and EASs. Remarkably, Africans seem to carry extremely lower frequencies of SARS-CoV-1 susceptibility alleles, reaching to 32-fold decrease compared to other populations. Conclusion: Multiple genetic variants, which could potentially modulate SARS-CoV-2 infection, are significantly variable between populations, with the lowest frequency observed among Africans. Our results highlight the importance of exploring population genetics to understand and predict COVID-19 outcomes. Indeed, further studies are needed to validate these findings as well as to identify new genetic determinants linked to SARS-CoV-2.
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"Complex alleles of splicing variants in Mendelian diseases." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-246.
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Affenzeller, Michael, Stefan Wagner, Stephan Winkler, and Andreas Beham. "Analysis of the dynamics of allele distribution for some selected GA-variants." In 2010 IEEE 14th International Conference on Intelligent Engineering Systems. IEEE, 2010. http://dx.doi.org/10.1109/ines.2010.5483852.
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Lee, Joyce, Andy Wing Chun PANG, Caspar Groß, Jakob Admard, Elena Buena-Atienza, Stephan Ossowski, Thomas Anantharaman, Mark Oldakowski, Sven Bocklandt, and Alex Hastie. "Abstract 1329: Identifying low allele frequency somatic variants using the Saphyr System." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-1329.
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Smatti, Maria Khalid, Yasser Al-Sarraj, Omar Albagha, and Hadi Yassine. "Genetic Susceptibility to Infectious Diseases in the Qatari Population." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0092.
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Background: Infectious diseases (IDs) account for 8% of deaths annually in Qatar, and therefore, represent a significant challenge for public health. Interestingly, the spread and severity of viral infections vary considerably between individuals and populations. The most recent example is SARS-CoV-2, which ranges from mild/asymptomatic to a severe respiratory syndrome. It has been previously reported that polymorphisms in genes linked to immunity can influence individuals’ responses to infections as observed in tuberculosis, influenza, and HIV; however, studies exploring causal host genetic variants in IDs are still limited and dramatically skewed with regard to population inclusion. In fact, the genetic susceptibility to IDs in the Qatari population is largely unknown. Aim: To perform a comprehensive genetic screening to investigate the presence and frequency of variants previously associated with various infections in the Qatari population. Methods: Whole-genome sequencing was previously performed for 18,000 QBB participants using Illumina HiSeq X Ten1 sequencers. The initial data processing and quality assessment of the raw data has also been performed and variant calling files (VCF) were created. We were granted the access to the VCF files of 6,218 sequenced samples. The genetic variant data was then converted to PLINK file format using PLINK-1.9. Standardized quality-assurance and quality control (QA/QC) methods were followed to generate high quality and confidence on both SNPs and sample levels. The final file used for calculating allele frequency contained 6,047 subjects. Additionally, list of infections-related SNPs that were previously reported in the literature and deposited in GWAS catalog was extracted and used to calculate and compare the allelic frequency in the Qatari genomes compared to other populations. Results: The frequency of infections-related SNPs in the Qatari population was significantly lower for most infections. Most variants (78%) showed negative fold change in the Qatari genomes. Only 22% of all variants were more prevalent in Qatari population compared to others. The most significant differences were observed in genes related to TB and HIV (200-940 and 160-710 fold change, respectively). Conclusion: This study reports a lower susceptibility of the Qatari population to IDs in general. Nonetheless, this might also indicate the presence of unknown Qatari-unique variants and hence, highlights the need for further investigation in future GWAS.
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Alexiadis, Vassilios, Tim Watanaskul, Karena Kosco, and Lyle Arnold. "Abstract 3198: The CEE-Selector Assay: A tool for the identification of rare allele variants." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3198.
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de Oliveira Junior, G. A., M. Spehar, F. S. Schenkel, C. F. Baes, and G. Gorjanc. "198. Long-term changes in genetic mean and genic variance and underlying allele frequencies in breeding programmes." In World Congress on Genetics Applied to Livestock Production. The Netherlands: Wageningen Academic Publishers, 2022. http://dx.doi.org/10.3920/978-90-8686-940-4_198.
Full textReports on the topic "Allele variances"
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Brayton, Kelly A., Varda Shkap, Guy H. Palmer, Wendy C. Brown, and Thea Molad. Control of Bovine Anaplasmosis: Protective Capacity of the MSP2 Allelic Repertoire. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7699838.bard.
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Anaplasmosis is an arthropod-borne disease of cattle caused by the rickettsia Anaplasmamarginale and is an impediment to efficient production of healthy livestock in both Israel and the United States. Currently, the only effective vaccines are derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Consequently, development of a safe, effective vaccine is a high priority. Despite its drawbacks as a live, blood-based vaccine, the Israel vaccine strain protects against disease upon challenge with wild-type A. marginale in extensive experimental trials and during 50 years of deployment in Israel. Field studies in Australia and Argentina indicate that this protection is broadly effective. Thus, to identify antigens for development of a safe and effective recombinant vaccine, we have used a comparative genomics approach by sequencing the Israel vaccine strain and searching for shared surface antigens with sequenced wild-type U.S. strains. We have focused on Msp2, the immune-dominant but antigenically variable surface protein, based on shared structure among strains and demonstration that antibody from cattle immunized with the Israel vaccine strain binds Msp2 from the genetically and geographically distinct U.S. St. Maries strain, consistent with the ability to protect against St. Maries challenge. Importantly, we have defined the full repertoire of Msp2 simple variants encoded by the vaccine strain and hypothesize that a recombinant vaccine encoding this full repertoire will induce protection equivalent to that induced by the live vaccine strain. Any escape from immunity by generation of complex Msp2 variants is predicted to carry a severe fitness cost that prevents high-level bacteremia and disease— consistent with the type of protection induced by the live vaccine strain. We tested the hypothesis that the Msp2 simple variant repertoires in wild-type A. marginale strains are recognized by antibody from cattle immunized with the Israel vaccine strain and that immunization with the vaccine strain Msp2 repertoire can recapitulate the protection provided by the vaccine strain upon challenge with Israel and U.S. strains of A. marginale. Our findings demonstrate that a set of conserved outer membrane proteins are recognized by immune serum from A. centrale vaccinated animals but that this set of proteins does not include Msp2. These findings suggest that “subdominant” immunogens are required for vaccine induced protection.
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Döring, Thomas. Öffentliche Verschuldung (finanz-)psychologisch betrachtet. Sonderforschungsgruppe Institutionenanalyse, 2019. http://dx.doi.org/10.46850/sofia.9783941627734.
Full textAbstract:
Die öffentliche Verschuldung gilt aus ökonomischer Sicht als ein ebenso bedeutsames wie problematisches Finanzierungsinstrument des Staates. Diese Einsicht speist sich nicht allein aus den Staatsschuldenkrisen eines Teils der Mitgliedsstaaten des Europäischen Währungsraums infolge der jüngsten Wirtschafts- und Finanzkrise 2008/2009. Vielmehr handelt es sich bei diesen Krisen um ein historisch wiederkehrendes Phänomen, von dem auch andere Länder innerhalb und außerhalb Europas betroffen waren und sind. Blickt man allein auf solche Krisen, übersieht man leicht, dass die Finanzierung des Staates mittels Schuldaufnahme etwas Alltägliches darstellt. Mit dem vorliegenden Beitrag soll der Frage nachgegangen werden, wie sich die in den ausgewiesenen Daten widerspiegelnde Nutzung des staatlichen Verschuldungsinstruments ökonomisch erklären lässt. Zu diesem Zweck wer-den zunächst in knapper Form die bekannten finanzwissenschaftlichen Begründungen der öffentlichen Schuldaufnahme einschließlich der bestehenden politökonomischen Erklärungsversuche des zeitlichen Entwicklungsverlaufs der Staatsverschuldung dargestellt (Kapitel 2). Dieser Überblick bildet zugleich den Ausgangspunkt, um in einem weiteren Schritt danach zu fragen, welche zusätzlichen Erkenntnisse zum staatlichen Verschuldungsverhalten sich aus einer Berücksichtigung von psychologischen Überlegungen, wie sie sowohl im Rahmen der Steuer- und Finanzpsychologie als auch in neueren Ansätzen der Verhaltensökonomik formuliert werden, gewinnen lassen (Kapitel 3). Im Mittelpunkt stehen dabei das Phänomen der Schuldenillusion, seine verschiedenen Varianten, aber auch damit im Zusammenhang stehende Reizschwellen- und Reaktanz-Effekte, Wahrnehmungsverzerrungen sowie fehlende Lernprozesse auf Seiten der Bürger ebenso wie ein möglicher kognitiver Kontrollverlust bei den Regierungsakteuren. Daran anknüpfend werden abschließend einige finanzpolitische Schlussfolgerungen zur Begrenzung der öffentlichen Verschuldung abgeleitet (Kapitel 4).
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Weller, Joel I., Derek M. Bickhart, Micha Ron, Eyal Seroussi, George Liu, and George R. Wiggans. Determination of actual polymorphisms responsible for economic trait variation in dairy cattle. United States Department of Agriculture, January 2015. http://dx.doi.org/10.32747/2015.7600017.bard.
Full textAbstract:
The project’s general objectives were to determine specific polymorphisms at the DNA level responsible for observed quantitative trait loci (QTLs) and to estimate their effects, frequencies, and selection potential in the Holstein dairy cattle breed. The specific objectives were to (1) localize the causative polymorphisms to small chromosomal segments based on analysis of 52 U.S. Holstein bulls each with at least 100 sons with high-reliability genetic evaluations using the a posteriori granddaughter design; (2) sequence the complete genomes of at least 40 of those bulls to 20 coverage; (3) determine causative polymorphisms based on concordance between the bulls’ genotypes for specific polymorphisms and their status for a QTL; (4) validate putative quantitative trait variants by genotyping a sample of Israeli Holstein cows; and (5) perform gene expression analysis using statistical methodologies, including determination of signatures of selection, based on somatic cells of cows that are homozygous for contrasting quantitative trait variants; and (6) analyze genes with putative quantitative trait variants using data mining techniques. Current methods for genomic evaluation are based on population-wide linkage disequilibrium between markers and actual alleles that affect traits of interest. Those methods have approximately doubled the rate of genetic gain for most traits in the U.S. Holstein population. With determination of causative polymorphisms, increasing the accuracy of genomic evaluations should be possible by including those genotypes as fixed effects in the analysis models. Determination of causative polymorphisms should also yield useful information on gene function and genetic architecture of complex traits. Concordance between QTL genotype as determined by the a posteriori granddaughter design and marker genotype was determined for 30 trait-by-chromosomal segment effects that are segregating in the U.S. Holstein population; a probability of <10²⁰ was used to accept the null hypothesis that no segregating gene within the chromosomal segment was affecting the trait. Genotypes for 83 grandsires and 17,217 sons were determined by either complete sequence or imputation for 3,148,506 polymorphisms across the entire genome. Variant sites were identified from previous studies (such as the 1000 Bull Genomes Project) and from DNA sequencing of bulls unique to this project, which is one of the largest marker variant surveys conducted for the Holstein breed of cattle. Effects for stature on chromosome 11, daughter pregnancy rate on chromosome 18, and protein percentage on chromosome 20 met 3 criteria: (1) complete or nearly complete concordance, (2) nominal significance of the polymorphism effect after correction for all other polymorphisms, and (3) marker coefficient of determination >40% of total multiple-regression coefficient of determination for the 30 polymorphisms with highest concordance. The missense polymorphism Phe279Tyr in GHR at 31,909,478 base pairs on chromosome 20 was confirmed as the causative mutation for fat and protein concentration. For effect on fat percentage, 12 additional missensepolymorphisms on chromosome 14 were found that had nearly complete concordance with the suggested causative polymorphism (missense mutation Ala232Glu in DGAT1). The markers used in routine U.S. genomic evaluations were increased from 60,000 to 80,000 by adding markers for known QTLs and markers detected in BARD and other research projects. Objectives 1 and 2 were completely accomplished, and objective 3 was partially accomplished. Because no new clear-cut causative polymorphisms were discovered, objectives 4 through 6 were not completed.
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Sela, Hanan, Eduard Akhunov, and Brian J. Steffenson. Population genomics, linkage disequilibrium and association mapping of stripe rust resistance genes in wild emmer wheat, Triticum turgidum ssp. dicoccoides. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598170.bard.
Full textAbstract:
The primary goals of this project were: (1) development of a genetically characterized association panel of wild emmer for high resolution analysis of the genetic basis of complex traits; (2) characterization and mapping of genes and QTL for seedling and adult plant resistance to stripe rust in wild emmer populations; (3) characterization of LD patterns along wild emmer chromosomes; (4) elucidation of the multi-locus genetic structure of wild emmer populations and its correlation with geo-climatic variables at the collection sites. Introduction In recent years, Stripe (yellow) rust (Yr) caused by Pucciniastriiformis f. sp. tritici(PST) has become a major threat to wheat crops in many parts of the world. New races have overcome most of the known resistances. It is essential, therefore, that the search for new genes will continue, followed by their mapping by molecular markers and introgression into the elite varieties by marker-assisted selection (MAS). The reservoir of genes for disease and pest resistance in wild emmer wheat (Triticumdicoccoides) is an important resource that must be made available to wheat breeders. The majority of resistance genes that were introgressed so far in cultivated wheat are resistance (R) genes. These genes, though confering near-immunity from the seedling stage, are often overcome by the pathogen in a short period after being deployed over vast production areas. On the other hand, adult-plant resistance (APR) is usually more durable since it is, in many cases, polygenic and confers partial resistance that may put less selective pressure on the pathogen. In this project, we have screened a collection of 480 wild emmer accessions originating from Israel for APR and seedling resistance to PST. Seedling resistance was tested against one Israeli and 3 North American PST isolates. APR was tested on accessions that did not have seedling resistance. The APR screen was conducted in two fields in Israel and in one field in the USA over 3 years for a total of 11 replicates. We have found about 20 accessions that have moderate stripe rust APR with infection type (IT<5), and about 20 additional accessions that have novel seedling resistance (IT<3). We have genotyped the collection using genotyping by sequencing (GBS) and the 90K SNP chip array. GBS yielded a total 341K SNP that were filtered to 150K informative SNP. The 90K assay resulted in 11K informative SNP. We have conducted a genome-wide association scan (GWAS) and found one significant locus on 6BL ( -log p >5). Two novel loci were found for seedling resistance. Further investigation of the 6BL locus and the effect of Yr36 showed that the 6BL locus and the Yr36 have additive effect and that the presence of favorable alleles of both loci results in reduction of 2 grades in the IT score. To identify alleles conferring adaption to extreme climatic conditions, we have associated the patterns of genomic variation in wild emmer with historic climate data from the accessions’ collection sites. The analysis of population stratification revealed four genetically distinct groups of wild emmer accessions coinciding with their geographic distribution. Partitioning of genomic variance showed that geographic location and climate together explain 43% of SNPs among emmer accessions with 19% of SNPs affected by climatic factors. The top three bioclimatic factors driving SNP distribution were temperature seasonality, precipitation seasonality, and isothermality. Association mapping approaches revealed 57 SNPs associated with these bio-climatic variables. Out of 21 unique genomic regions controlling heading date variation, 10 (~50%) overlapped with SNPs showing significant association with at least one of the three bioclimatic variables. This result suggests that a substantial part of the genomic variation associated with local adaptation in wild emmer is driven by selection acting on loci regulating flowering. Conclusions: Wild emmer can serve as a good source for novel APR and seedling R genes for stripe rust resistance. APR for stripe rust is a complex trait conferred by several loci that may have an additive effect. GWAS is feasible in the wild emmer population, however, its detection power is limited. A panel of wild emmer tagged with more than 150K SNP is available for further GWAS of important traits. The insights gained by the bioclimatic-gentic associations should be taken into consideration when planning conservation strategies.
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Bennett, Alan B., Arthur A. Schaffer, Ilan Levin, Marina Petreikov, and Adi Doron-Faigenboim. Manipulating fruit chloroplasts as a strategy to improve fruit quality. United States Department of Agriculture, January 2013. http://dx.doi.org/10.32747/2013.7598148.bard.
Full textAbstract:
The Original Objectives were modified and two were eliminated to reflect the experimental results: Objective 1 - Identify additional genetic variability in SlGLK2 and IPin wild, traditional and heirloom tomato varieties Objective 2 - Determine carbon balance and horticultural characteristics of isogenic lines expressing functional and non-functional alleles of GLKsand IP Background: The goal of the research was to understand the unique aspects of chloroplasts and photosynthesis in green fruit and the consequences of increasing the chloroplast capacity of green fruit for ripe fruit sugars, yield, flavor and nutrient qualities. By focusing on the regulation of chloroplast formation and development solely in fruit, our integrated knowledge of photosynthetic structures/organs could be broadened and the results of the work could impact the design of manipulations to optimize quality outputs for the agricultural fruit with enhanced sugars, nutrients and flavors. The project was based on the hypothesis that photosynthetic and non-photosynthetic plastid metabolism in green tomato fruit is controlled at a basal level by light for minimal energy requirements but fruit-specific genes regulate further development of robust chloroplasts in this organ. Our BARD project goals were to characterize and quantitate the photosynthesis and chloroplast derived products impacted by expression of a tomato Golden 2- like 2 transcription factor (US activities) in a diverse set of 31 heirloom tomato lines and examine the role of another potential regulator, the product of the Intense Pigment gene (IP activities). Using tomato Golden 2-like 2 and Intense Pigment, which was an undefined locus that leads to enhanced chloroplast development in green fruit, we sought to determine the benefits and costs of extensive chloroplast development in fruit prior to ripening. Major conclusions, solutions, achievements: Single nucleotide polymorphisms in the promoter, coding and intronicSlGLK2 sequences of 20 heirloom tomato lines were identified and three SlGLK2 promoter lineages were identified; two lineages also had striped fruit variants. Lines with striped fruit but no shoulders were not identified. Green fruit chlorophyll and ripe fruit soluble sugar levels were measured in 31 heirloom varieties and fruit size correlates with ripe fruit sugars but dark shoulders does not. A combination of fine mapping, recombinant generation, RNAseq expression and SNP calling all indicated that the proposed localization of a single locus IP on chr 10 was incorrect. Rather, the IP line harbored 11 separate introgressions from the S. chmielewskiparent, scattered throughout the genome. These introgressions harbored ~3% of the wild species genome and no recombinant consistently recovered the IP parental phenotype. The 11 introgressions were dissected into small combinations in segregating recombinant populations. Based on these analyses two QTL for Brix content were identified, accounting for the effect of increased Brix in the IP line. Scientific and agricultural implications: SlGLK2 sequence variation in heirloom tomato varieties has been identified and can be used to breed for differences in SlGLK2 expression and possibly in the green striped fruit phenotype. Two QTL for Brix content have been identified in the S. chmielewskiparental line and these can be used for increasing soluble solids contents in breeding programs.
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Chamovitz, Daniel A., and Albrecht G. Von Arnim. eIF3 Complexes and the eIF3e Subunit in Arabidopsis Development and Translation Initiation. United States Department of Agriculture, September 2009. http://dx.doi.org/10.32747/2009.7696545.bard.
Full textAbstract:
The original working hypothesis of our proposal was that The “e” subunit of eIF3 has multiple functions from both within the nucleus and in the cytoplasm. Within this model, we further hypothesized that the “e” subunit of eIF3 functions in translation as a repressor. We proposed to test these hypotheses along the following specific aims: 1) Determine the subcellular localization of the interaction between eIF3e and other eIF3 subunits, or the COP9 signalosome. 2) Elucidate the biological significance of the varied subcellular localizations of eIF3e through generating Arabidopsis eIF3e alleles with altered subcellular localization. 3.) Purify different eIF3e complexes by tandem affinity purification (TAP). 4) Study the role of eIF3e in translational repression using both in vitro and in planta assays. eIF3 is an evolutionarily ancient and essential component of the translational apparatus in both the plant and animal kingdoms. eIF3 is the largest, and in some ways the most mysterious, of the translation factors. It is a multi-subunit protein complex that has a structural/scaffolding role in translation initiation. However, despite years of study, only recently have differential roles for eIF3 in the developmental regulation of translation been experimentally grounded. Furthermore, the roles of individual eIF3 subunits are not clear, and indeed some, such as the “e” subunit may have roles independent of translation initiation. The original three goals of the proposal were technically hampered by a finding that became evident during the course of the research – Any attempt to make transgenic plants that expressed eIF3e wt or eIF3e variants resulted in seedling lethality or seed inviability. That is, it was impossible to regenerate any transgenic plants that expressed eIF3e. We did manage to generate plants that expressed an inducible form of eIF3e. This also eventually led to lethality, but was very useful in elucidating the 4th goal of the research (Yahalom et al., 2008), where we showed, for the first time in any organism, that eIF3e has a repressory role in translation. In attempt to solve the expression problems, we also tried expression from the native promoter, and as such analyzed this promoter in transgenic plants (Epel, 2008). As such, several additional avenues were pursued. 1) We investigated protein-protein interactions of eIF3e (Paz-Aviram et al., 2008). 2) The results from goal #4 led to a novel hypothesis that the interaction of eIF3e and the CSN meets at the control of protein degradation of nascent proteins. In other words, that the block in translation seen in csn and eIF3e-overexpressing plants (Yahalom et al., 2008) leads to proteasome stress. Indeed we showed that both over expression of eIF3e and the csn mutants lead to the unfolded protein response. 3) We further investigated the role of an additional eIF3 subunit, eIF3h, in transalational regulation in the apical meristem (Zhou et al., 2009). Epel, A. (2008). Characterization of eIF3e in the model plant Arabidopsis thaliana. In Plant Sciences (Tel Aviv, Tel Aviv University). Paz-Aviram, T., Yahalom, A., and Chamovitz, D.A. (2008). Arabidopsis eIF3e interacts with subunits of the ribosome, Cop9 signalosome and proteasome. Plant Signaling and Behaviour 3, 409-411. Yahalom, A., Kim, T.H., Roy, B., Singer, R., von Arnim, A.G., and Chamovitz, D.A. (2008). Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation. Plant J 53, 300-311. Zhou, F., Dunlap, J.R., and von Arnim, A.G. The translation initiation factor subunit eIF3h is .1 involved in Arabidopsis shoot apical meristem maintenance and auxin response. (submitted to Development).
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Hansen, Peter J., Zvi Roth, and Jeremy J. Block. Improving oocyte competence in dairy cows exposed to heat stress. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598163.bard.
Full textAbstract:
Original Objectives. The overall goal is to develop methods to increase pregnancy rate in lactating dairy cows exposed to heat stress through methods that minimize damage to the oocyte and embryo caused by heat stress. Objectives were as follows: (1) examine the protective effects of melatonin on developmental competence of oocytes exposed to elevated temperature in vitro; (2) test whether melatonin feeding can improve developmental competence of oocytes in vivo and, if so, whether effects are limited to the summer or also occur in the absence of heat stress; and (3) evaluate the effectiveness of improving fertility by facilitating follicular turnover in the summer and winter. Revised Objectives. (1) Examine protective effects of melatonin and follicular fluid on developmental competence of oocytes exposed to elevated temperature in vitro; (2) examine the protective effects of melatonin on developmental competence of embryos exposed to elevated temperature in vitro; (3) evaluate effectiveness of improving fertility by administering human chorionicgonadotropin (hCG) to increase circulating concentrations of progesterone and evaluate whether response to hCG depends upon genotype for four mutations reported to be related to cow fertility; and (4) identify genes with allelic variants that increase resistance of embryos to heat shock. Background. The overall hypothesis is that pregnancy success is reduced by heat stress because of damage to the oocyte and cleavage-stage embryo mediated by reactive oxygen species (ROS), and that fertility can be improved by provision of antioxidants or by removing follicles containing oocytes damaged by heat stress. During the study, additional evidence from the literature indicated the potential importance of treatment with chorionicgonadotropin to increase fertility of heat- stressed cows and results from other studies in our laboratories implicated genotype as an important determinant of cow fertility. Thus, the project was expanded to evaluate hCG treatment and to identify whether fertility response to hCG depended upon single nucleotide polymorphisms (SNP) in genes implicated as important for cow fertility. We also evaluated whether a SNP in a gene important for cellular resistance to heat stress (HSPA1L, a member of the heat shock protein 70 family) is important for embryonic resistance to elevated temperature. Major conclusions, solutions & achievements. Results confirmed that elevated temperature increases ROS production by the oocyte and embryo and that melatonin decreases ROS. Melatonin reduced, but did not completely block, damaging effects of heat shock on the oocyte and had no effect on development of the embryo. Melatonin was protective to the oocyte at 0.1-1 μM, a concentration too high to be achieved in cows. It was concluded that melatonin is unlikely to be a useful molecule for increasing fertility of heat-stressed cows. Treatment with hCG at day 5 after breeding increased first-service pregnancy rate for primiparous cows but not for multiparous cows. Thus, hCG could be useful for increasing fertility in first-parity cows. The effectiveness of hCG depended upon genotype for a SNP in COQ9, a gene encoding for a mitochondrial-function protein. This result points the way to future efforts to use genetic information to identify populations of cows for which hormone treatments will be effective or ineffective. The SNP in HSPA1L was related to embryonic survival after heat shock. Perhaps, genetic selection for mutations that increase cellular resistance to heat shock could be employed to reduce effects of heat stress on fertility. Implications, both scientific and agricultural. This project has resulted in abandonment of one possible approach to improve fertility of the heat-stressed cow (melatonin therapy) while also leading to a method for improving fertility of primiparous cows exposed to heat stress (hCG treatment) that can be implemented on farms today. Genetic studies have pointed the way to using genetic information to 1) tailor hormonal treatments to cow populations likely to respond favorably and 2) select animals whose embryos have superior resistance to elevated body temperatures.