Journal articles on the topic 'Allele variances'
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1
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.
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Korol, A. B., Y. I. Ronin, Y. Tadmor, A. Bar-Zur, V. M. Kirzhner, and E. Nevo. "Estimating variance effect of QTL: an important prospect to increase the resolution power of interval mapping." Genetical Research 67, no. 2 (April 1996): 187–94. http://dx.doi.org/10.1017/s0016672300033632.
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SummaryEqual variances within quantitative trait locus (QTL) groups in the segregating population are a usual simplifying assumption in QTL mapping. The objective of this paper is to demonstrate the advantages of taking into account potential variance effect of QTLs within the framework of standard interval mapping approach. Using backcross case as an example, we show that the resolution power of the analysis may be increased in the presence of variance effect, if the latter is allowed for in the model. For a putative QTL (say, A/a) one can compare two situations, (i) and (ii) . It was found that, if the variance effect of A/a is large enough, then in spite of the necessity to evaluate an increased number of parameters, the more correctly specified model provides an increase in the resolution power, as compared to the situation (i). This is not unexpected, if either in (ii) is lower than from (i). But our conclusion holds even if . These advantages are illustrated on sweet corn data data (F3 families of F2 genotypes). In particular, the log-likelihood test statistics and the parameter estimates obtained for a QT locus in the distal region of chromosome 2 show that the allele enhancing the trait is recessive over the opposite allele simultaneously for the mean value and variance.
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Shtark, M. B., Ye N. Zagoruyko, S. P. Kovalenko, and O. S. Shubina. "Psychopharmacogenetic approach in therapy of affective disorders depressive spectrum." Bulletin of Siberian Medicine 8, no. 1(2) (February 28, 2009): 5–9. http://dx.doi.org/10.20538/1682-0363-2009-1(2)-5-9.
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This article is dedicated to rationale of pharmacotherap y in the treatment of depressive disorders. Differentiation of allele gene variances, linked to metabolism of antidepressants, was conducted. Genetic status of patients and individual parameters of antidepressant’s metabolism took into account in every clinical case. Results of this research can allowed to forecast effectivene ss, compliance and tolerance of antidepressants.
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Pérez-Enciso, Miguel, Alex Clop, Josep M. Folch, Armand Sánchez, Maria A. Oliver, Cristina Óvilo, C. Barragán, Luis Varona, and José L. Noguera. "Exploring Alternative Models for Sex-Linked Quantitative Trait Loci in Outbred Populations: Application to an Iberian × Landrace Pig Intercross." Genetics 161, no. 4 (August 1, 2002): 1625–32. http://dx.doi.org/10.1093/genetics/161.4.1625.
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Abstract We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between outbred lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F2 cross between Iberian × Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component.
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Bürger, R. "Linkage and the maintenance of heritable variation by mutation-selection balance." Genetics 121, no. 1 (January 1, 1989): 175–84. http://dx.doi.org/10.1093/genetics/121.1.175.
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Abstract The role of linkage in influencing heritable variation maintained through a balance between mutation and stabilizing selection is investigated for two different models. In both cases one trait is considered and the interactions within and between loci are assumed to be additive. Contrary to most earlier investigations of this problem no a priori assumptions on the distribution of genotypic values are imposed. For a deterministic two-locus two-allele model with recombination and mutation, related to the symmetric viability model, a complete nonlinear analysis is performed. It is shown that, depending on the recombination rate, multiple stable equilibria may coexist. The equilibrium genetic and genic variances are calculated. For a polygenic trait in a finite population with a possible continuum of allelic effects a simulation study is performed. In both models the equilibrium genetic and genic variances are roughly equal to the house-of-cards prediction or its finite population counterpart as long as the recombination rate is not extremely low. However, negative linkage disequilibrium builds up. If the loci are very closely linked the equilibrium additive genetic variance is slightly lower than the house-of-cards prediction, but the genic variance is much higher. Depending on whether the parameters are in favor of the house-of-cards or the Gaussian approximation, different behavior of the genetic system occurs with respect to linkage.
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Xu, Shizhong. "Computation of the Full Likelihood Function for Estimating Variance at a Quantitative Trait Locus." Genetics 144, no. 4 (December 1, 1996): 1951–60. http://dx.doi.org/10.1093/genetics/144.4.1951.
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The proportion of alleles identical by descent (IBD) determines the genetic covariance between relatives, and thus is crucial in estimating genetic variances of quantitative trait loci (QTL). However, IBD proportions at QTL are unobservable and must be inferred from marker information. The conventional method of QTL variance analysis maximizes the likelihood function by replacing the missing IBDs by their conditional expectations (the expectation method), while in fact the full likelihood function should take into account the conditional distribution of IBDs (the distribution method). The distribution method for families of more than two sibs has not been obvious because there are n(n – 1)/2 IBD variables in a family of size n, forming an n × n symmetrical matrix. In this paper, I use four binary variables, where each indicates the event that an allele from one of the four grandparents has passed to the individual. The IBD proportion between any two sibs is then expressed as a function of the indicators. Subsequently, the joint distribution of the IBD matrix is derived from the distribution of the indicator variables. Given the joint distribution of the unknown IBDs, a method to compute the full likelihood function is developed for families of arbitrary sizes.
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Mei, Hong, Baoming Yin, Wenhong Yang, Jingli Zhang, Hongyan Lu, Xiaobin Qi, Wenhua Mei, Hongzhong Zhang, and Jianduan Zhang. "Associations between Gene-Gene Interaction and Overweight/Obesity of 12-Month-Old Chinese Infants." BioMed Research International 2022 (March 7, 2022): 1–10. http://dx.doi.org/10.1155/2022/1499454.
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Background. Childhood overweight and obesity (OW/OB) is a worldwide public health problem, and its genetic risks remain unclear. Objectives. To investigate risks of OW/OB associated with genetic variances in SEC16B rs543874 and rs10913469, BDNF rs11030104 and rs6265, NT5C2 rs11191580, PTBP2 rs11165675, ADCY9 rs2531995, FAM120A rs7869969, KCNQ1 rs2237892, and C4orf33 rs2968990 in Chinese infants at 12-month old. Methods. We conducted a case-control study with 734 infants included at delivery and followed up to 12-month old. The classification and regression tree analysis were used to generate the structure of the gene-gene interactions, while the unconditional multivariate logistic regression models were applied to analyze the single SNP, gene-gene interactions, and cumulative effects of the genotypes on OW/OB, adjusted for potential confounders. Results. There were 219 (29.84%) OW/OB infants. Rs543874 G allele and rs11030104 AA genotype increased the risk of OW/OB in 12-month-old infants ( P < 0.05 ). Those carrying both rs11030104 AA genotype and rs10913469 C allele had 4.3 times greater OW/OB than those carrying rs11030104 G allele, rs11191580 C allele, rs11165675 A allele, and rs543874 AA genotype. Meanwhile, the risk of OW/OB increased with the number of the risk genotypes individuals harbored. Conclusions. Rs543874, rs11030104, and rs11191580 were associated with OW/OB in 12-month-old Chinese infants, and the three SNPs together with rs10913469 and rs11165675 had a combined effect on OW/OB.
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Gharrett, A. J., and W. W. Smoker. "Two Generations of Hybrids between Even- and Odd-Year Pink Salmon (Oncorhynchus gorbuscha): A Test for Outbreeding Depression?" Canadian Journal of Fisheries and Aquatic Sciences 48, no. 9 (September 1, 1991): 1744–49. http://dx.doi.org/10.1139/f91-206.
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Hybrids of genetically isolated odd- and even-year pink salmon (Oncorhynchus gorbuscha) from the same stream were made by fertilizing eggs with cryopreserved milt. Anadromous first-generation (F1) hybrids and controls returned to the hatchery at equal rates (153 of 5483 and 160 of 5492, respectively), on the same average date, and with the same size. However, variances of F1 size (female length and weight and male length) exceeded variances of control sizes, suggesting increased genetic variation in F1's. Only 11 of 5165 F2's returned. F2's were similar meristically and in size to fish of their parents' generation, but were bilaterally more asymmetric in number of gill rakers and in combined numbers of gill rakers and of branchiostegals. Increased F1 variation followed by low F2 returns and increased bilateral asymmetry is a pattern to be expected when coadapted allele complexes are disrupted by outbreeding depression.
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Zeng, Z. B., and C. C. Cockerham. "Mutation models and quantitative genetic variation." Genetics 133, no. 3 (March 1, 1993): 729–36. http://dx.doi.org/10.1093/genetics/133.3.729.
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Abstract Analyses of evolution and maintenance of quantitative genetic variation depend on the mutation models assumed. Currently two polygenic mutation models have been used in theoretical analyses. One is the random walk mutation model and the other is the house-of-cards mutation model. Although in the short term the two models give similar results for the evolution of neutral genetic variation within and between populations, the predictions of the changes of the variation are qualitatively different in the long term. In this paper a more general mutation model, called the regression mutation model, is proposed to bridge the gap of the two models. The model regards the regression coefficient, gamma, of the effect of an allele after mutation on the effect of the allele before mutation as a parameter. When gamma = 1 or 0, the model becomes the random walk model or the house-of-cards model, respectively. The additive genetic variances within and between populations are formulated for this mutation model, and some insights are gained by looking at the changes of the genetic variances as gamma changes. The effects of gamma on the statistical test of selection for quantitative characters during macroevolution are also discussed. The results suggest that the random walk mutation model should not be interpreted as a null hypothesis of neutrality for testing against alternative hypotheses of selection during macroevolution because it can potentially allocate too much variation for the change of population means under neutrality.
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Lara, Letícia A. de C., Ivan Pocrnic, Thiago de P. Oliveira, R. Chris Gaynor, and Gregor Gorjanc. "Temporal and genomic analysis of additive genetic variance in breeding programmes." Heredity 128, no. 1 (December 15, 2021): 21–32. http://dx.doi.org/10.1038/s41437-021-00485-y.
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AbstractGenetic variance is a central parameter in quantitative genetics and breeding. Assessing changes in genetic variance over time as well as the genome is therefore of high interest. Here, we extend a previously proposed framework for temporal analysis of genetic variance using the pedigree-based model, to a new framework for temporal and genomic analysis of genetic variance using marker-based models. To this end, we describe the theory of partitioning genetic variance into genic variance and within-chromosome and between-chromosome linkage-disequilibrium, and how to estimate these variance components from a marker-based model fitted to observed phenotype and marker data. The new framework involves three steps: (i) fitting a marker-based model to data, (ii) sampling realisations of marker effects from the fitted model and for each sample calculating realisations of genetic values and (iii) calculating the variance of sampled genetic values by time and genome partitions. Analysing time partitions indicates breeding programme sustainability, while analysing genome partitions indicates contributions from chromosomes and chromosome pairs and linkage-disequilibrium. We demonstrate the framework with a simulated breeding programme involving a complex trait. Results show good concordance between simulated and estimated variances, provided that the fitted model is capturing genetic complexity of a trait. We observe a reduction of genetic variance due to selection and drift changing allele frequencies, and due to selection inducing negative linkage-disequilibrium.
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Yao, Danyu, Waqas Ijaz, Yi Liu, Jinghuang Hu, Wentao Peng, Bowen Zhang, Xiaolan Wen, et al. "Identification of a Pm4 Allele as a Powdery Mildew Resistance Gene in Wheat Line Xiaomaomai." International Journal of Molecular Sciences 23, no. 3 (January 21, 2022): 1194. http://dx.doi.org/10.3390/ijms23031194.
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Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive foliar diseases of wheat. In this study, we combined the bulked segregant RNA sequencing (BSR-seq) and comparative genomics analysis to localize the powdery mildew resistance gene in Chinese landrace Xiaomaomai. Genetic analysis of F1 plants from a crossing of Xiaomaomai × Lumai23 and the derived F2 population suggests that a single recessive gene, designated as pmXMM, confers the resistance in this germplasm. A genetic linkage map was constructed using the newly developed SNP markers and pmXMM was mapped to the distal end of chromosome 2AL. The two flanking markers 2AL15 and 2AL34 were closely linked to pmXMM at the genetic distance of 3.9 cM and 1.4 cM, respectively. Using the diagnostic primers of Pm4, we confirmed that Xiaomaomai carries a Pm4 allele and the gene function was further validated by the virus-induced gene silencing (VIGS). In addition, we systematically analyzed pmXMM in comparison with the other Pm4 alleles. The results suggest that pmXMM is identical to Pm4d and Pm4e at sequence level. Pm4b is also not different from Pm4c according to their genome/amino acid sequences. Only a few nucleotide variances were detected between pmXMM and Pm4a/b, which indicate the haplotype variation of the Pm4 gene.
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Mielenz, N., and L. Schüler. "Langzeitselektion bei asymmetrischer Merkmalsverteilung." Archives Animal Breeding 43, no. 5 (October 10, 2000): 421–30. http://dx.doi.org/10.5194/aab-43-421-2000.
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Abstract. Title of the paper: Long-term selection by asymmetric trait distribution A quantitative trait is assumed to be genetically affected by a polygenic effect and a major effect of a Single dialellic locus. Such a model is called mixed model of inheritance and the identified gene is denoted as quantitative trait locus (QTL). By choosing the part of the QTL-variance, the degree of dominance and the frequency of the favourable allele it is possible to generate distributions with given level of asymmetry characterised by skewness and kurtosis. If the ratio of QTL- and phenotypic variance is small (less than 8%), then genotype-environment interaction can be used in the mixed inheritance model to explain values of skewness and kurtosis estimated with poultry data. The Situation is considered where the environmental variances given for the three QTL-genotypes show a wide ränge. In most of these cases the short- and long-term selection does not effects the high values for skewness and kurtosis over multiple generations. Further the ratio of response to selection and the difference of selection depends on the selection intensity.
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Dawkins, Bryan A., Trang T. Le, and Brett A. McKinney. "Theoretical properties of distance distributions and novel metrics for nearest-neighbor feature selection." PLOS ONE 16, no. 2 (February 8, 2021): e0246761. http://dx.doi.org/10.1371/journal.pone.0246761.
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The performance of nearest-neighbor feature selection and prediction methods depends on the metric for computing neighborhoods and the distribution properties of the underlying data. Recent work to improve nearest-neighbor feature selection algorithms has focused on new neighborhood estimation methods and distance metrics. However, little attention has been given to the distributional properties of pairwise distances as a function of the metric or data type. Thus, we derive general analytical expressions for the mean and variance of pairwise distances for Lq metrics for normal and uniform random data with p attributes and m instances. The distribution moment formulas and detailed derivations provide a resource for understanding the distance properties for metrics and data types commonly used with nearest-neighbor methods, and the derivations provide the starting point for the following novel results. We use extreme value theory to derive the mean and variance for metrics that are normalized by the range of each attribute (difference of max and min). We derive analytical formulas for a new metric for genetic variants, which are categorical variables that occur in genome-wide association studies (GWAS). The genetic distance distributions account for minor allele frequency and the transition/transversion ratio. We introduce a new metric for resting-state functional MRI data (rs-fMRI) and derive its distance distribution properties. This metric is applicable to correlation-based predictors derived from time-series data. The analytical means and variances are in strong agreement with simulation results. We also use simulations to explore the sensitivity of the expected means and variances in the presence of correlation and interactions in the data. These analytical results and new metrics can be used to inform the optimization of nearest neighbor methods for a broad range of studies, including gene expression, GWAS, and fMRI data.
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Wang, Gang, Wenju Zhou, Deping Kong, Zongshuai Qu, Maowen Ba, Jinguang Hao, Tao Yao, et al. "Studying APOE ɛ4 Allele Dose Effects with a Univariate Morphometry Biomarker." Journal of Alzheimer's Disease 85, no. 3 (February 1, 2022): 1233–50. http://dx.doi.org/10.3233/jad-215149.
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Background: A univariate neurodegeneration biomarker (UNB) based on MRI with strong statistical discrimination power would be highly desirable for studying hippocampal surface morphological changes associated with APOE ɛ4 genetic risk for AD in the cognitively unimpaired (CU) population. However, existing UNB work either fails to model large group variances or does not capture AD induced changes. Objective: We proposed a subspace decomposition method capable of exploiting a UNB to represent the hippocampal morphological changes related to the APOE ɛ4 dose effects among the longitudinal APOE ɛ4 homozygotes (HM, N = 30), heterozygotes (HT, N = 49) and non-carriers (NC, N = 61). Methods: Rank minimization mechanism combined with sparse constraint considering the local continuity of the hippocampal atrophy regions is used to extract group common structures. Based on the group common structures of amyloid-β (Aβ) positive AD patients and Aβ negative CU subjects, we identified the regions-of-interest (ROI), which reflect significant morphometry changes caused by the AD development. Then univariate morphometry index (UMI) is constructed from these ROIs. Results: The proposed UMI demonstrates a more substantial statistical discrimination power to distinguish the longitudinal groups with different APOE ɛ4 genotypes than the hippocampal volume measurements. And different APOE ɛ4 allele load affects the shrinkage rate of the hippocampus, i.e., HM genotype will cause the largest atrophy rate, followed by HT, and the smallest is NC. Conclusion: The UMIs may capture the APOE ɛ4 risk allele-induced brain morphometry abnormalities and reveal the dose effects of APOE ɛ4 on the hippocampal morphology in cognitively normal individuals.
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Kondrashov, Alexey S. "Dynamics of unconditionally deleterious mutations: Gaussian approximation and soft selection." Genetical Research 65, no. 2 (April 1995): 113–21. http://dx.doi.org/10.1017/s0016672300033139.
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SummaryThis paper studies the influence of two opposite forces, unidirectional unconditionally deleterious mutations and directional selection against them, on an amphimictic population. Mutant alleles are assumed to be equally deleterious and rare, so that homozygous mutations can be ignored. Thus, a genotype is completely described by its value with respect to a quantitative trait x, the number of mutations it carries, while a population is described by its distribution p(x) with mean M[p] and variance V[p] = σ2[p]. When mutations are only slightly deleterious, so that M » 1, before selection p(x) is close to Gaussian with any mode of selection. I assume that selection is soft in the sense that the fitness of a genotype depends on the difference between its value of x and M, in units of σ. This leads to a simple system of equations connecting the values of M and V in successive generations. This system has a unique and stable equilibrium, where U is the genomic deleterious mutation rate, δ is the selection differential for x in units of σ, and p is the ratio of variances of p(x) after and before selection. Both δ and ρ are parameters of the mode of soft selection, and do not depend on M or V. In an equilibrium population, the selection coefficient against a mutant allele is ŝ = δ2[U(2–ρ)]−1. The mutation load can be tolerable only if the genome degradation rate υ = U/σ is below 2. Other features of mutation-selection equilibrium are also discussed.
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Pirchner, F. "Schätzung inzuchtwirksamer (effektiver) Populationsgrößen aus Genfrequenzschwankungen bei Bayerischem Fleckvieh und Tiroler Grauvieh." Archives Animal Breeding 45, no. 4 (October 10, 2002): 331–39. http://dx.doi.org/10.5194/aab-45-331-2002.
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Abstract. Title of the paper: Estimating effective population size (Ne) from allele frequency changes in Bavarian Simmental (FV) and Tyrolean Grey (GV) cattle Frequencies of 10 to 16 alleles of blood group, hemo- and lactoprotein loci were estimated for FV in 1960, 1986 and 200, for GV in 1969, 1979 and 1998. Rates of inbreeding in the intervening periods and Ne`s were derived from Wahlund variances. The Ne`s for the two part periods of FV, spanning 2.2 resp. 4.1 generations, were 152 resp. 147, for the whole period of 6.25 generation intervals 373. This is due to the opposing signs of the changes in the two part periods and it may reflect the large influence of a top sire on the gene pool in the first period and ensueing change to a FV gene reservoir similar to that in 1960. For GV the Ne`of the two part periods were 139 and 56, for the whole 97, roughly in agreement with the one expected from the two short periods. The lower Ne of the second part period agrees well with an estimate by the inbreeding increment in roughly the same time period.
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Turner, Thomas F., John P. Wares, and John R. Gold. "Genetic Effective Size Is Three Orders of Magnitude Smaller Than Adult Census Size in an Abundant, Estuarine-Dependent Marine Fish (Sciaenops ocellatus)." Genetics 162, no. 3 (November 1, 2002): 1329–39. http://dx.doi.org/10.1093/genetics/162.3.1329.
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Abstract Using eight microsatellite loci and a variety of analytical methods, we estimated genetic effective size (Ne) of an abundant and long-lived marine fish species, the red drum (Sciaenops ocellatus), in the northern Gulf of Mexico (Gulf). The ratio Ne/N, where short-term variance Ne was estimated via the temporal method from shifts in allele-frequency data over four cohorts and where N reflected a current estimate of adult census size in the northern Gulf, was ∼0.001. In an idealized population, this ratio should approximate unity. The extraordinarily low value of Ne/N appears to arise from high variance in individual reproductive success and perhaps more importantly from variance in productivity of critical spawning and nursery habitats located in spatially discrete bays and estuaries throughout the northern Gulf. An estimate of Ne based on a coalescent approach, which measures long-term, inbreeding effective size, was four orders of magnitude lower than the estimate of current census size, suggesting that factors presently driving Ne/N to low values among red drum in the northern Gulf may have operated similarly in the past. Models that predict Ne/N exclusively from demographic and life-history features will seriously overestimate Ne if variance in reproductive success and variance in productivity among spatially discrete demes is underestimated. Our results indicate that these variances, especially variance in productivity among demes, must be large for red drum. Moreover, our study indicates that vertebrate populations with enormous adult census numbers may still be at risk relative to decline and extinction from genetic factors.
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Uimari, Pekka, and Ina Hoeschele. "Mapping-Linked Quantitative Trait Loci Using Bayesian Analysis and Markov Chain Monte Carlo Algorithms." Genetics 146, no. 2 (June 1, 1997): 735–43. http://dx.doi.org/10.1093/genetics/146.2.735.
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A Bayesian method for mapping linked quantitative trait loci (QTL) using multiple linked genetic markers is presented. Parameter estimation and hypothesis testing was implemented via Markov chain Monte Carlo (MCMC) algorithms. Parameters included were allele frequencies and substitution effects for two biallelic QTL, map positions of the QTL and markers, allele frequencies of the markers, and polygenic and residual variances. Missing data were polygenic effects and multi-locus marker-QTL genotypes. Three different MCMC schemes for testing the presence of a single or two linked QTL on the chromosome were compared. The first approach includes a model indicator variable representing two unlinked QTL affecting the trait, one linked and one unlinked QTL, or both QTL linked with the markers. The second approach incorporates an indicator variable for each QTL into the model for phenotype, allowing or not allowing for a substitution effect of a QTL on phenotype, and the third approach is based on model determination by reversible jump MCMC. Methods were evaluated empirically by analyzing simulated granddaughter designs. All methods identified correctly a second, linked QTL and did not reject the one-QTL model when there was only a single QTL and no additional or an unlinked QTL.
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Zhou, Yinsheng, Han Zhang, and Yaning Yang. "CSHAP: efficient haplotype frequency estimation based on sparse representation." Bioinformatics 35, no. 16 (December 24, 2018): 2827–33. http://dx.doi.org/10.1093/bioinformatics/bty1040.
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Abstract Motivation Estimating haplotype frequencies from genotype data plays an important role in genetic analysis. In silico methods are usually computationally involved since phase information is not available. Due to tight linkage disequilibrium and low recombination rates, the number of haplotypes observed in human populations is far less than all the possibilities. This motivates us to solve the estimation problem by maximizing the sparsity of existing haplotypes. Here, we propose a new algorithm by applying the compressive sensing (CS) theory in the field of signal processing, compressive sensing haplotype inference (CSHAP), to solve the sparse representation of haplotype frequencies based on allele frequencies and between-allele co-variances. Results Our proposed approach can handle both individual genotype data and pooled DNA data with hundreds of loci. The CSHAP exhibits the same accuracy compared with the state-of-the-art methods, but runs several orders of magnitude faster. CSHAP can also handle with missing genotype data imputations efficiently. Availability and implementation The CSHAP is implemented in R, the source code and the testing datasets are available at http://home.ustc.edu.cn/∼zhouys/CSHAP/. Supplementary information Supplementary data are available at Bioinformatics online.
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Gordon, Derek, Yaning Yang, Chad Haynes, Stephen J. Finch, Nancy R. Mendell, Abraham M. Brown, and Vahram Haroutunian. "Increasing Power for Tests of Genetic Association in the Presence of Phenotype and/or Genotype Error by Use of Double-Sampling." Statistical Applications in Genetics and Molecular Biology 3, no. 1 (January 6, 2004): 1–32. http://dx.doi.org/10.2202/1544-6115.1085.
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Phenotype and/or genotype misclassification can: significantly increase type II error probabilities for genetic case/control association, causing decrease in statistical power; and produce inaccurate estimates of population frequency parameters. We present a method, the likelihood ratio test allowing for errors (LRTae) that incorporates double-sample information for phenotypes and/or genotypes on a sub-sample of cases/controls. Population frequency parameters and misclassification probabilities are determined using a double-sample procedure as implemented in the Expectation-Maximization (EM) method. We perform null simulations assuming a SNP marker or a 4-allele (multi-allele) marker locus. To compare our method with the standard method that makes no adjustment for errors (LRTstd), we perform power simulations using a 2^k factorial design with high and low settings of: case/control samples, phenotype/genotype costs, double-sampled phenotypes/genotypes costs, phenotype/genotype error, and proportions of double-sampled individuals. All power simulations are performed fixing equal costs for the LRTstd and LRTae methods. We also consider case/control ApoE genotype data for an actual Alzheimer's study.The LRTae method maintains correct type I error proportions for all null simulations and all significance level thresholds (10%, 5%, 1%). LRTae average estimates of population frequencies and misclassification probabilities are equal to the true values, with variances of 10e-7 to 10e-8. For power simulations, the median power difference LRTae-LRTstd at the 5% significance level is 0.06 for multi-allele data and 0.01 for SNP data. For the ApoE data example, the LRTae and LRTstd p-values are 5.8 x 10e-5 and 1.6 x 10e-3, respectively. The increase in significance is due to adjustment in the LRTae for misclassification of the most commonly reported risk allele. We have developed freely available software that performs our LRTae statistic.
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Uimari, Pekka, Georg Thaller, and Ina Hoeschele. "The Use of Multiple Markers in a Bayesian Method for Mapping Quantitative Trait Loci." Genetics 143, no. 4 (August 1, 1996): 1831–42. http://dx.doi.org/10.1093/genetics/143.4.1831.
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Abstract Information on multiple linked genetic markers was used in a Bayesian method for the statistical mapping of quantitative trait loci (QTL). Bayesian parameter estimation and hypothesis testing were implemented via Markov chain Monte Carlo algorithms. Variables sampled were the augmented data (marker-QTL genotypes, polygenic effects), an indicator variable for linkage or nonlinkage, and the parameters. The parameter vector included allele frequencies at the markers and the QTL, map distances of the markers and the QTL, QTL substitution effect, and polygenic and residual variances. The criterion for QTL detection was the marginal posterior probability of a QTL being located on the chromosome carrying the markers, The method was evaluated empirically by analyzing simulated granddaughter designs consisting of 2000 sons, 20 related sires, and their ancestors.
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Menčik, Sven, Vlado Vuković, Mario Modrić, Marija Špehar, Mario Ostović, Velimir Sušić, Igor Štoković, Marko Samardžija, and Anamaria Ekert Kabalin. "PRLR-AluI Gene Polymorphism And Litter Size Traits In Highly Prolific Line Of Topigs 20 Sows." Acta Veterinaria 65, no. 4 (December 1, 2015): 463–76. http://dx.doi.org/10.1515/acve-2015-0039.
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AbstractThe objective of the present study was to identify the Prolactin Receptor (PRLR) gene polymorphism related to litter size traits. The study included 101 Topigs 20 line of sows with 426 litters. The traits studied were: Total Number of Born (TNB), Number of Born Alive (NBA), Number of Still Born (NSB), and Number of MUMmified (NMUM) piglets. Polymorphism was identified with the polymerase chain reaction-restriction fragment length polymorphism method. Allelic and genotype frequencies and deviation from Hardy-Weinberg equilibrium were verified with the chi-square test. Analysis of litter size traits was performed using the General Linear Model, which included the potential environmental effects. Additive and dominant allele variances were observed by the regression procedure. In the studied population of sows, the frequency of heterozygotes (0.5149) for PRLR gene exceeded the total number of AA (0.0198) and BB (0.4653) homozygotes, which resulted in a high proportion of B allele (0.7228). The results for PRLR showed statistically significant (P<0.05) differences in first parity sows between BB and AB genotypes for TNB and NBA. Significant differences(P<0.05) were recorded in third parity sows between BB and AB genotypes for NBA, and in AA genotypeversusAB and BB genotypes for NMUM. The fourth and subsequent parity sows of AA genotype had a significantly higher (P<0.05) rate of NBA as compared with those of AB and BB genotypes. In all parities analysed, the difference between the BB and AB genotypes for NBA was statistically significant (P<0.05). Interpretation of the results at the levels of phenotypes and either additive or dominant variance was quite difficult due to the small number of AA homozygous sows. The calculation model yielded a significant effect (P<0.05) as well as tendency (P<0.1) for the mentioned effects except for age at first farrowing.
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Jansen, Ritsert C., David L. Johnson, and Johan A. M. Van Arendonk. "A Mixture Model Approach to the Mapping of Quantitative Trait Loci in Complex Populations With an Application to Multiple Cattle Families." Genetics 148, no. 1 (January 1, 1998): 391–99. http://dx.doi.org/10.1093/genetics/148.1.391.
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Abstract A mixture model approach is presented for the mapping of one or more quantitative trait loci (QTLs) in complex populations. In order to exploit the full power of complete linkage maps the simultaneous likelihood of phenotype and a multilocus (all markers and putative QTLs) genotype is computed. Maximum likelihood estimation in our mixture models is implemented via an Expectation-Maximization algorithm: exact, stochastic or Monte Carlo EM by using a simple and flexible Gibbs sampler. Parameters include allele frequencies of markers and QTLs, discrete or normal effects of biallelic or multiallelic QTLs, and homogeneous or heterogeneous residual variances. As an illustration a dairy cattle data set consisting of twenty half-sib families has been reanalyzed. We discuss the potential which our and other approaches have for realistic multiple-QTL analyses in complex populations.
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Wright, A. J., and C. Clark Cockerham. "SELECTION WITH PARTIAL SELFING. I. MASS SELECTION." Genetics 109, no. 3 (March 1, 1985): 585–97. http://dx.doi.org/10.1093/genetics/109.3.585.
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ABSTRACT The expected responses to mass selection carried out before or after reproduction in a population whose members all have a fixed probability of self pollination (s) are formulated using covariances of relatives and their component quadratic functions for a model with arbitrary additive and dominance effects. The response measured in the first generation offspring after selection (immediate gain) can differ from that retained when the population has regained equilibrium (permanent gain). The population mean behaves in a predictable manner during the return to equilibrium, and its value at any time can be predicted from earlier generations. The permanent gain from selection after reproduction is always (1 + s)/2 times as large as that from selection before reproduction, but the relationship of the immediate gains depends on the genetic model assumed.—Numerical analysis applied to a model with two alleles per locus and varying allele frequencies, dominance ratios and numbers of loci showed that the proportion of the immediate gain retained at equilibrium was reduced with the large inbreeding depression associated with increasing dominance levels and numbers of loci and was generally lower for selection after reproduction than before. In the absence of information as to the magnitude of genetic variances and inbreeding depression in species reproducing by partial selfing, the importance of this phenomenon is unknown.
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Farah, Michel Marques, Marina Rufino Salinas Fortes, Matthew Kelly, Laercio Ribeiro Porto-Neto, Camila Tangari Meira, Luis Orlando Duitama Carreño, Ricardo da Fonseca, and Stephen Stewart Moore. "Accuracy of genomic selection predictions for hip height in Brahman cattle using different relationship matrices." Pesquisa Agropecuária Brasileira 53, no. 6 (June 2018): 717–26. http://dx.doi.org/10.1590/s0100-204x2018000600008.
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Abstract: The objective of this work was to evaluate the effects of genomic information on the genetic evaluation of hip height in Brahman cattle using different matrices built from genomic and pedigree data. Hip height measurements from 1,695 animals, genotyped with high-density SNP chip or imputed from 50 K high-density SNP chip, were used. The numerator relationship matrix (NRM) was compared with the H matrix, which incorporated the NRM and genomic relationship (G) matrix simultaneously. The genotypes were used to estimate three versions of G: observed allele frequency (HGOF), average minor allele frequency (HGMF), and frequency of 0.5 for all markers (HG50). For matrix comparisons, animal data were either used in full or divided into calibration (80% older animals) and validation (20% younger animals) datasets. The accuracy values for the NRM, HGOF, and HG50 were 0.776, 0.813, and 0.594, respectively. The NRM and HGOF showed similar minor variances for diagonal and off-diagonal elements, as well as for estimated breeding values. The use of genomic information resulted in relationship estimates similar to those obtained based on pedigree; however, HGOF is the best option for estimating the genomic relationship matrix and results in a higher prediction accuracy. The ranking of the top 20% animals was very similar for all matrices, but the ranking within them varies depending on the method used.
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MÄKI-TANILA, A. "An overview on quantitative and genomic tools for utilising dominance genetic variation in improving animal production." Agricultural and Food Science 16, no. 2 (December 4, 2008): 188. http://dx.doi.org/10.2137/145960607782219337.
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In addition to genetic progress made by selection on additive genetic values, short-term gains can be produced by recovering possible inbreeding depression or utilising putative overdominance. These are both caused mainly by dominance genetic variation which can be quantified using mixed model methodology. Inbreeding brings along a requirement for extra parameterisation in expressing and estimating dominance variance. The extra parameters specify how dominance is affecting the mean and (co)variances among inbred animals. The full description for breed crosses contains a very large set of parameters. The benefits from crossbreeding are highest with widely deviating allele frequencies between the breeds. Maximisation of heterosis can be done only on a temporary basis as a continued exploitation leads to stagnation in the overall genetic progress. Therefore efficient methods with immediate returns are needed to find the most promising breeds jointly with the most potential mating pairs. One possibility is the use of genomic tools in assessing populations for crossbreeding and in searching for major genes mediating dominance variation. The analyses are providing markers that can be used in choosing mating pairs that produce desirable dominance deviations in analysed marker brackets. Genome-wide marker sets can be used for discovering genome segments with maximum heterosis effect. The phenotypic records are available for such analyses, soon are also the large marker sets and their genotypes: the analytical tools need developers.;
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Maia, Aline de Holanda Nunes, and Durval Dourado Neto. "Probabilistic tools for assessment of pest resistance risk associated to insecticidal transgenic crops." Scientia Agricola 61, no. 5 (October 2004): 481–85. http://dx.doi.org/10.1590/s0103-90162004000500003.
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One of the main risks associated to transgenic crops expressing Bacillus thuringiensis (Bt) toxins is the evolution of pest resistance. The adoption of Bt crops requires environmental risk assessment that includes resistance risk estimation, useful for definition of resistance management strategies aiming to delay resistance evolution. In this context, resistance risk is defined as the probability of the Bt toxin resistance allele frequency (RFreq) exceeding a critical value (CriticalFreq). Mathematical simulation models have been used to estimate (RFreq) over pest generations. In 1998, Caprio developed a deterministic simulation model with few parameters that can be used to obtain RFreq point estimates from point information about model parameters and decision variables involved in that process. In this work, the resistance risk was estimated using Caprio´s model, by incorporating uncertainty to the resistance allele initial frequency (InitialFreq). The main objective was to evaluate the influence of different probability distribution functions on the risk estimates. The simulation results showed that the influence of InitialFreq input distributions on the risk estimates changes along pest generations. The risk estimates considering input Normal distribution for InitialFreq are similar to those ones obtained considering Triangular distribution if their variances are equal. The use of Uniform distribution instead the Normal or Triangular due to the lack of information about InitialFreq leads to an overestimation of risk estimates for the initial generations and sub estimation for the generations after the one for which the critical frequency is achieved.
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Huang, William C. W., Yi-MeiJoy Lin, Ching Che J. Chiu, Chia-Huei Chiu, and Fu-Sheng Chang. "Evaluation of Age-Gene Correlation and the Association with Hypertriglyceridemia Using Adiponectin Receptor Single Nucleotide Polymorphism: A Potential Genetic Screening to Lower Risk of Vascular Disease in Young Asian Males." Higher Education Studies 7, no. 2 (May 2, 2017): 61. http://dx.doi.org/10.5539/hes.v7n2p61.
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Purpose: This study was to investigate whether there is an age dependent effect on the association between ADIPPOR1 SNP and hypertriglyceridemia for each gender.Materials and Methods: 116 individuals aged 20 and above who claimed to be healthy were enrolled and grouped into male and female populations. Blood samples were taken to determine hypertriglyceridemia and genomic variants. Sample t-tests were performed for basic comparison. To ascertain the contribution of genetic variants and age to lipid metabolism, a multivariate logistic regression analysis was conducted to identify the correlates for hypertriglyceridemia adjusting for life styles.Results: For males, individuals with hypertriglyceridemia tended to be younger (p-value=0.02), less stressed (0.05), and have a higher proportion of ADIPOR1 minor allele carriers (0.03). However, no significant differences were found in age, stress, diet, and genetic variances in females. In regression analysis, males showed age-gene correlation with 1.5 times higher detection of hypertriglyceridemia risk when both factors were considered. In contrast, females showed no correlation between age-gene. In addition, age was positively associated with hypertriglyceridemia in females while males showed an inverse association.Conclusion: Our findings presented data that suggests age may be a contributing factor to the association between ADIPOR1 and hypertriglyceridemia in males while age showed a significant inverse association with hypertriglyceridemia. Thus, age-gene correlation may be implied during primary practice to encourage lifestyle adjustments by screening for ADIPOR1 SNP minor allele carriers to prevent cerebrovascular disease in males.
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Martinez-Hernandez, A., E. E. Perez-Guerrero, M. A. Macias-Islas, C. A. Nava-Valdivia, A. Villagomez-Vega, B. Contreras-Haro, Y. E. Garcia-Ortega, et al. "Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study." Journal of Immunology Research 2021 (December 23, 2021): 1–11. http://dx.doi.org/10.1155/2021/7523997.
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Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls ( p = 0.009 ). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression ( p = 0.88 ). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls ( p = 0.05 ). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 ( p = 0.65 ). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls ( p = 0.03 ). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 ( p = 0.63 ). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.
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Masud, Rizwan, Aleem Ul Haq Khan, Aiman Farogh Anjum, Ghazala Jawwad, Zahid Azeem, Haider Zaigham Baqai, and Shoaib Naiyar Hashmi. "The Connotation of Variances in the Risk Predictors, Medications, Homocysteine, and Homocysteine Pathway Gene Polymorphisms with CVA/Stroke." Global Medical Genetics 07, no. 04 (December 2020): 113–20. http://dx.doi.org/10.1055/s-0041-1722884.
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AbstractCerebrovascular accidents (CVAs) are vascular multifactorial, multigenic ailments with intricate genetic, environmental risk influences. The present study aimed to establish affiliation of CVAs/stroke with blood parameters, differences in prescribed drugs consumption, and with differences in homocysteine pathway genes polymorphisms. The participants in study included controls n = 251, transient ischemic attack (TIA) patients n = 16, and stroke cases n = 122, respectively, (total participants, n = 389). The analyzed single nucleotide polymorphisms (SNPs) included C677T(rs1801133), A1298C(rs1801131) of methylene tetrahydrofolate reductase (MTHFR), A2756G(rs1805087) of methyl tetrahydrofolate homocysteine methyltransferase/methionine synthase (MS), and the A192G(rs662) of paraoxonase 1(PON1) genes, all validated by tetra-primer allele refractory mutation system polymerase chain reaction (T-ARMS-PCR). The insertion deletion (I/D; rs4646994) polymorphism in angiotensin converting enzyme (ACE) gene was analyzed using routine PCR. All studied traits were scrutinized through analysis of variance (ANOVA), and later through regression analysis. Through ANOVA and multiple comparison, there was association of CVA with serum homocysteine, cholesterol, and with diastolic blood pressure readings. When data was subjected to regression, serum homocysteine and diastolic blood pressure (significant through ANOVA), as well as two additional traits, high-density lipoproteins (HDL), and rs1801133 MTHFR SNP sustained statistical significance and noteworthy odds in relation to CVA and stroke. The ailments affecting cerebral vasculature are mutifactorial, whereby genes, proteins, and environmental cues all exert cumulative effects enhancing CVA risk. The current study emphasizes that SNPs and variation in circulating biomarkers can be used for screening purposes and for reviewing their effects in stroke/CVA-linked risk progression.
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Iacobucci, Ilaria, Anna Ferrari, Alexander Kohlmann, Cristina Papayannidis, Claudia Venturi, Margherita Perricone, Maria Chiara Fontana, et al. "Loss of Heterozygosity At the C Wild-Type Allele of rs1042522 in the TP53 Gene Frequently Occurs During Progression of Adult BCR-ABL1 Positive Acute Lymphoblastic Leukemia (ALL)." Blood 120, no. 21 (November 16, 2012): 2497. http://dx.doi.org/10.1182/blood.v120.21.2497.2497.
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Abstract Abstract 2497 Introduction: The gene TP53 encoding the tumour suppressor protein p53 is among the most commonly mutated genes in human cancer. TP53 tumour-associated alterations often cause dramatic defects in p53 function and correlate with increased malignancy, dismal survival and resistance to treatment. In contrast, only a small fraction, if any, of the >200 single nucleotide polymorphisms (SNPs) of TP53 in human populations are expected to cause measurable perturbation of p53 function. Aim: Since the pattern, frequency and significance of TP53 aberrations and SNPs in adult BCR-ABL1 positive ALL have still to be investigated, in this study we used a massively parallel pyrosequencing technique to address these issues. Patients and methods: Forty-three adults with BCR-ABL1 positive ALL were analyzed (median age 63 years, range 18–84). Twenty-four cases (56%) were analyzed only at the time of diagnosis, four cases (9%) only at the time of relapse and fifteen cases (35%) at both time points. Massively parallel pyrosequencing in picoliter-sized wells was used to allow highly-sensitive deep-sequencing detecting molecular aberrations at a low burden rate. As part of the IRON (Interlaboratory RObustness of Next generation sequencing) II study network, we applied preconfigured plates including primers for TP53 (exons 4 to 11) and allowing the simultaneous screening of 11 patients, each being recognized by a unique molecular identifier. For each plate, after generating 88 amplicons, 8 per each patient, PCR products were purified using Agencourt AMPure XP beads and Biomek 3000 Laboratory Automation Workstation (Beckam Coulter) and quantified using the Quant-iT PicoGreen kit (Invitrogen). All amplicons were pooled in an equimolar ratio to generate one single library. Subsequent emulsion PCR and amplicon sequencing was performed according to the manufacturer's recommendations on the Genome Sequencer Junior Instrument (Roche Applied Science). Data were analyzed using the GS Amplicon Variant Analyzer software version 2.7 (Roche Applied Science). For the detection of variances, filters were set to display sequence variances occurring in more than 5% of bidirectional reads per amplicon in at least one sample. Results: On average, we generated 63,068 sequencing beads (key pass wells) per plate (range, 50,798-79,486) with a median read length range between 284 and 365 base pairs. The median number of generated reads per case was 5,413 (range, 687-9,604). The median number of reads per amplicon was as follows: exon 4: 275 (range, 0–888), exon 5: 222 (range, 0–1,013); exon 6: 316 (range, 84–854); exon 7: 317 (range, 5–720); exon 8: 313 (range, 0–784); exon 9: 215 (range, 0–785); exon 10: 328 (range, 0–826), exon 11: 447 (range, 0–1,511). Forward and reverse reads were homogeneously distributed allowing a sensitive detection of variances. In total, 8 single nucleotide variations were identified. All variances, except for one nucleotide substitution occurring at position 7576743 (GRCh37/hg19), were found to represent SNPs according to the NCBI dbSNP Build 137. They included: rs1042522 C/G (41/43, 95%) and rs1800370 A/G (1/43, 2%) in exon 4, rs1800372 A/G (2/43, 5%) in exon 6, rs1625895 A/G (42/43, 98%) in intron 6–7, rs12947788 A/G (3/43, 7%) and rs12951053 A/C (4/43, 9%) in intron 7–8 and rs1800899 C/T (1/43, 2%) in intron 9–10. Interestingly, in 2 cases (12%) loss of heterozygosity occurred at the relapse at the C wild-type allele of rs1042522 in leukemia cells. The same mechanism has been identified for one case at the wild-type allele of rs1625895 with the expansion of the variant form at relapse. Both rs1042522 and rs1625895 have been described to alter p53 functionality and increase susceptibility to cancers (Whibley et al.,2009). Although the role of rs12947788 and rs12951053 has not yet deeply investigated, in our study they were found in 3 cases that all relapsed. Conclusion: Comprehensive next generation deep-sequencing of TP53 by a screening assay set up within the IRON II study has demonstrated its ability to efficiently detect TP53 variant. The inactivation of the wild-type allelic forms of rs1042522 and rs1625895, altering the p53 functionality, may serve as an important background for leukemia progression in BCR-ABL1-positive ALL. Disclosures: Kohlmann: MLL Munich Leukemia Laboratory: Employment. Luppi:CELGENE CORPORATION: Research Funding. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Baccarani:ARIAD, Novartis, Bristol Myers-Squibb, and Pfizer: Consultancy, Honoraria, Speakers Bureau. Martinelli:NOVARTIS: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; PFIZER: Consultancy; ARIAD: Consultancy.
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Stoddart, J. A., and J. F. Taylor. "Genotypic diversity: estimation and prediction in samples." Genetics 118, no. 4 (April 1, 1988): 705–11. http://dx.doi.org/10.1093/genetics/118.4.705.
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Abstract We show that a commonly used statistic of genotypic diversity can be used to reflect one form of deviation from panmixia, viz. clonal reproduction, by comparing observed and predicted sample statistics. The characteristics of the statistic, in particular its relationship with population genotypic diversity, are formalised and a method of predicting the genotypic diversity of a sample drawn from a panmictic population using allelic frequencies and sample size is developed. The sensitivity of some possible tests of significance of the deviation from panmictic expectations is examined using computer simulations. Goodness-of-fit tests are robust but produce an unacceptably high level of type II error. With means and variances calculated either from Monte Carlo simulations or from distributional and series approximations, t-tests perform better than goodness-of-fit tests. Under simulation, both forms of t-test exhibit acceptable rates of type I error. Rates of type II are usually large when allele frequencies are severely skewed although the latter test performs the better in those conditions.
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Kong, Xiango, Lukas Simon, Katrina Leung, Michael Holinstat, Chad Shaw, Paul F. Bray, and Leonard C. Edelstein. "Identification of the Genetic Mechanism Responsible for Racially-Dimorphic Expression of the Thrombin-Receptor Regulator, Pctp." Blood 126, no. 23 (December 3, 2015): 415. http://dx.doi.org/10.1182/blood.v126.23.415.415.
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Abstract Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with various healthy and pathological phenotypes. The majority of these SNPs do not fall into protein-coding regions of the genome, leading to the hypothesis that variants in genomic regulatory regions are critical regulators of physiology. Efforts by the ENCODE project and others to annotate the genome have enabled researchers to better identify and test SNPs for their functional effect on gene expression. We now report the identification of a SNP responsible for the racially differential expression of phosphatidylcholine transfer p (PCTP), a protein we have previously identified as a regulator of the human platelet thrombin receptor, protease activated receptor 4 (PAR4). In the Platelet RNA and eXpression 1 (PRAX1) study, we learned that platelets from black subjects were more active in response to signaling through the PAR4 receptor and contained approximately four times more PCTP mRNA and 50% more PC-TP protein as compared to platelets from white subjects. PCTP levels are significantly associated platelet PAR4 reactivity even after accounting for a racially dimorphic PAR4 polymorphism (Ala120Thr) that alters the receptor's function. We obtained from the 154 PRAX1 subjects genome wide platelet mRNA expression profiles and 4.3 million genotypes. Using this expression and genotype data, we were able to perform an expression Quantitative Trait Locus (eQTL) analysis to identify single nucleotide polymorphisms associated with the expression level of genes located within 50kb of the variant. This analysis revealed 16 highly linked SNPs associated with PCTP levels at genome-wide significance (P<10-6). eQTL SNPs can influence gene expression through a variety of mechanisms: (1) Altering the core promoter; (2) Altering the binding site of transcriptional regulators such as a transcription factors (TFs); (3) Altering RNA stability signals such as miRNA binding sites. Because none of the PCTP eQTL SNPs fall within the annotated core promoter, we reasoned the causative SNPs would fall within predicted transcription factor binding sites or miRNA target sites. To prioritize the 16 candidate SNPs for functional testing, we annotated each one according to the following criteria: (1) The SNP fell within a predicted binding site for a platelet-expressed TF or miRNA; (2) ChIP-Seq data from megakaryocytes, CD34+ hematopoietic stem cells or K562 erythroleukemia cells indicated TF binding in the region of the SNP; (3) The SNP falls in a regulatory region as indicated by epigenetic marks or DNAse hypersensitivity; (4) The allele frequency of the SNP is racially dimorphic, corresponding with PCTP expression. Using these criteria, we investigated rs2912553, a racially dimorphic SNP located in the first intron of PCTP. rs2912553 falls within a DNAse hypersensitive genomic locus that contains Lys4 monomethylated histone H3, a marker of enhancers. Cloning different sized fragments of this region 5' to a luciferase expression cassette replicated the observed PCTP expression pattern, with the vectors containing the allele most common in black subjects generating 2-8 fold higher luciferase expression than vectors containing the common allele in whites. In agreement with these results electromobility shift assays indicate that protein complexes have a threefold higher affinity for the common allele in blacks as compared to the common allele in whites (P=0.02), and that these complexes can be interrupted with an anti-GATA1 antibody. Concordantly, siRNA knockdown of GATA1 expression reduced luciferase activity in both alleles. Together, these data indicate that the racially dimorphic SNP, rs2912553, causes differential recruitment of a GATA-1 containing transcriptional complex that is responsible for higher PCTP expression in blacks. This suggests the hypothesis that these genetic variances contribute to the dissimilar thrombotic risk between blacks and whites. Future studies should address the utility of rs2912553 as a biomarker for diseases or drug effects that differ by race. Disclosures No relevant conflicts of interest to declare.
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Kondrashov, Alexey S. "Modifiers of mutation-selection balance: general approach and the evolution of mutation rates." Genetical Research 66, no. 1 (August 1995): 53–69. http://dx.doi.org/10.1017/s001667230003439x.
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SummaryA general approach is developed to estimate secondary selection at a modifier locus that influences some feature of a population under mutation-selection balance. The approach is based on the assumption that the properties of all available genotypes at this locus are similar. Then mutation-selection balance and weak associations between genotype distributions at selectable loci and the modifier locus are established rapidly. In contrast, changes of frequencies of the modifier genotypes are slow, and lead to only slow and small changes of the other features of the population. Thus, while these changes occur, the population remains in a state of quasi-equilibrium, where the mutation-selection balance and the associations between the selectable loci and the modifier locus are almost invariant. Selection at the modifier locus can be estimated by calculating quasiequilibrium values of these associations. This approach is developed for the situation where distributions of the number of mutations per genome within the individuals with a given modifier genotype are close to Gaussian. The results are used to study the evolution of the mutation rate. Because beneficial mutations are ignored, secondary selection at the modifier locus always diminishes the mutation rate. The coefficient of selection against an allele which increases the mutation rate by υ is approximately υδ2/[U(2−ρ)] = υŝ, where υ is the genomic deleterious mutation rate, δ is the selection differential of the number of mutations per individual in units of the standard deviation of the distribution of this number in the population, ρ is the ratio of variances of the number of mutations after and before selection, and ŝ is the selection coefficient against a mutant allele in the quasiequilibrium population. However, the decline of the mutation rate can be counterbalanced by the cost of fidelity, which can lead to an evolutionary equilibrium mutation rate.
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Valdes, A. M., M. Slatkin, and N. B. Freimer. "Allele frequencies at microsatellite loci: the stepwise mutation model revisited." Genetics 133, no. 3 (March 1, 1993): 737–49. http://dx.doi.org/10.1093/genetics/133.3.737.
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Abstract We summarize available data on the frequencies of alleles at microsatellite loci in human populations and compare observed distributions of allele frequencies to those generated by a simulation of the stepwise mutation model. We show that observed frequency distributions at 108 loci are consistent with the results of the model under the assumption that mutations cause an increase or decrease in repeat number by one and under the condition that the product Nu, where N is the effective population size and u is the mutation rate, is larger than one. We show that the variance of the distribution of allele sizes is a useful estimator of Nu and performs much better than previously suggested estimators for the stepwise mutation model. In the data, there is no correlation between the mean and variance in allele size at a locus or between the number of alleles and mean allele size, which suggests that the mutation rate at these loci is independent of allele size.
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Swystun, Laura L., Natalia Rydz, Colleen Notley, Jonathan J. Riches, Andrew D. Paterson, Robert R. Montgomery, Paula D. James, and David Lillicrap. "Genetic Variability of the CLEC4M Endothelial Lectin Receptor Modulates Binding and Internalization of Von Willebrand Factor and Contributes to Variance in Plasma VWF Levels." Blood 120, no. 21 (November 16, 2012): 16. http://dx.doi.org/10.1182/blood.v120.21.16.16.
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Abstract Abstract 16 Type 1 von Willebrand's Disease (VWD) can result from decreased synthesis or accelerated clearance of von Willebrand Factor (VWF), resulting in partial quantitative deficiency. Approximately 35% of individuals with Type 1 VWD do not have a putative mutation in their VWF gene, suggesting that genes other than VWF may contribute to the pathophysiology of this disease. Recently, the CHARGE GWAS meta-analysis identified single nucleotide polymorphisms in the gene encoding the C-type lectin domain family 4 member M (CLEC4M) as being significantly associated with plasma VWF levels in normal individuals. CLEC4M is a pathogen recognition receptor with a polymorphic extracellular neck region consisting of a variable number of tandem repeats (VNTR) (3 – 9 repeats). We hypothesize that CLEC4M binds to and clears VWF from the circulation, and that different CLEC4M VNTR alleles may contribute to differences in plasma levels of VWF in normal subjects and patients with Type 1 VWD. Previously, genotyping of 555 subjects (196 cases with type 1 VWD, and 362 family members) for the CLEC4M VNTR number showed that the most frequently documented alleles were VNTR 5 (29%), 6 (15%), and 7 (53%). Family-based association analysis on kindreds with type I VWD has demonstrated a significant excess transmission of VNTR 6 to the type I VWD phenotype (p=0.005) and an association of this VNTR allele with VWF:RCo (p=0.037). In the present studies, we have complemented this genetic association data with experiments to directly evaluate the ability of CLEC4M to bind and internalize VWF. Further, we characterized the ability of different CLEC4M VNTR alleles to facilitate VWF clearance. Binding of VWF to CLEC4M was assessed with a modified ELISA using a recombinant CLEC4M-Fc chimera. CLEC4M-Fc bound to Humate P (plasma-derived VWF-FVIII) in a dose-dependent manner. CLEC4M-Fc also bound to recombinant human VWF, and factor VIII-free plasma-derived VWF. CLEC4M-Fc demonstrated a 70% increase in binding to de-O-glycosylated Humate P (p=0.041), and a 75% decrease in binding to de-N-glycosylated Humate P (p=0.046) relative to controls. Additionally, pre-incubation of CLEC4M-Fc with the polysaccharide mannan attenuated binding to all VWF preparations by approximately 50%. Binding and internalization of VWF by HEK 293 cells stably expressing CLEC4M (VNTR allele 7) was assessed with immunofluorescence and ELISA. Binding of VWF co-localized with CLEC4M expression on HEK 293 cells. CLEC4M and VWF co-localized with early endosomal antigen-1, suggesting that CLEC4M participates in receptor-mediated endocytosis of VWF. CLEC4M-expressing cells bound and internalized VWF in a dose- and time-dependent manner relative to controls. Preincubation of CLEC4M expressing cells with mannan inhibited VWF binding and internalization by 50% (p=0.0088). The contribution of CLEC4M genetic variability to VWF binding and internalization was measured using HEK 293 cells expressing CLEC4M with 4, 6, 7, and 9 tandem repeats. Decreased binding and internalization of VWF was observed with cells expressing CLEC4M 4 and 9 tandem repeat constructs as compared to CLEC4M with 7 tandem repeats (CLEC4M 4 – 60% reduction, p < 0.001; CLEC4M 9 – 45% reduction, p=0.006). Cells expressing the CLEC4M VNTR combination 4 and 9, had a 55% decrease in binding and internalization of VWF relative to cells expressing CLEC4M with 7 VNTRs (p < 0.001). These VNTR associated differences in VWF binding/internalization were not accounted for by variances in the CLEC4M expression levels in the transfected HEK 293 cells. These studies demonstrate that the C-type lectin CLEC4M binds to and internalizes VWF through an N-glycan-dependent mechanism. Additionally, it provides further evidence that polymorphisms in the CLEC4M gene contribute to quantitative VWF deficiency. Disclosures: Montgomery: Gen-Probe/GTI Diagnostics: Consultancy; CSL Behring: Consultancy; Octapharma: Consultancy. James:CSL-Behring, Baxter, Bayer: Honoraria, Research Funding.
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Janss, L. L. G., J. A. M. Van Arendonk, and E. W. Brascamp. "Bayesian Statistical Analyses for Presence of Single Genes Affecting Meat Quality Traits in a Crossed Pig Population." Genetics 145, no. 2 (February 1, 1997): 395–408. http://dx.doi.org/10.1093/genetics/145.2.395.
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Presence of single genes affecting meat quality traits was investigated in F2 individuals of a cross between Chinese Meishan and Western pig lines using phenotypic measurements on 11 traits. A Bayesian approach was used for inference about a mixed model of inheritance, postulating effects of polygenic background genes, action of a biallelic autosomal single gene and various nongenetic effects. Cooking loss, drip loss, two pH measurements, intramuscular fat, shearforce and back-fat thickness were traits found to be likely influenced by a single gene. In all cases, a recessive allele was found, which likely originates from the Meishan breed and is absent in the Western founder lines. By studying associations between genotypes assigned to individuals based on phenotypic measurements for various traits, it was concluded that cooking loss, two pH measurements and possibly backfat thickness are influenced by one gene, and that a second gene influences intramuscular fat and possibly shearforce and drip loss. Statistical findings were supported by demonstrating marked differences in variances of families of fathers inferred as carriers and those inferred as noncarriers. It is concluded that further molecular genetic research effort to map single genes affecting these traits based on the same experimental data has a high probability of success.
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Johnson, James R., Adam L. Stell, Nicholas Kaster, Claudine Fasching, and Timothy T. O'Bryan. "Novel Molecular Variants of Allele I of theEscherichia coli P Fimbrial Adhesin GenepapG." Infection and Immunity 69, no. 4 (April 1, 2001): 2318–27. http://dx.doi.org/10.1128/iai.69.4.2318-2327.2001.
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ABSTRACT P fimbriae of extraintestinal pathogenic Escherichia coli mediate digalactoside-specific adherence via the tip adhesin molecule PapG, which occurs in three known variants (I to III), which are encoded by the corresponding three alleles of papG. In the present study, newly discovered variants of papG allele I and the respective wild-type source strains were characterized. One of the new papG allele I variants conferred a unique agglutination phenotype that combined the phenotypes associated withpapG alleles I, II, and III. Comparative hydrophilicity analysis of predicted PapG peptides revealed regions that might explain the observed phenotypic similarities and differences between the PapG variants. The new papG allele I variants occurred either as the sole papG allele or together with both papGalleles II and III, rather than with only papG allele III, as in archetypal strains J96 and CP9. They also occurred in the absence of the usual F13 papA allele. One of the newpapG allele I variants occurred in a serogroup O6 strain that, according to random amplified polymorphic DNA analysis, was phylogenetically distant from the “J96-like” clonal group ofE. coli O4:H5, which includes all previously identified examples of papG allele I. Cluster analysis of nucleotide and predicted peptide sequences suggested that papG allele I represents the earliest evolutionary branch from a commonpapG ancestor. These results demonstrate unexpected diversity within papG allele I and, together with previous findings, suggest that the J96-like clonal group of E. coliO4:H5 may represent the original source of papG within the species.
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Cane, Karen, H. A. Eagles, D. A. Laurie, Ben Trevaskis, Neil Vallance, R. F. Eastwood, N. N. Gororo, Haydn Kuchel, and P. J. Martin. "Ppd-B1 and Ppd-D1 and their effects in southern Australian wheat." Crop and Pasture Science 64, no. 2 (2013): 100. http://dx.doi.org/10.1071/cp13086.
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Photoperiod and vernalisation genes are important for the adaptation of wheat to variable environments. Previously, using diagnostic markers and a large, unbalanced dataset from southern Australia, we estimated the effects on days to heading of frequent alleles of Vrn-A1, Vrn-B1, and Vrn-D1, and also two allelic classes of Ppd-D1. These genes accounted for ~45% of the genotypic variance for that trait. We now extend these analyses to further alleles of Ppd-D1, and four alleles of Ppd-B1 associated with copy number. Variation in copy number of Ppd-B1 occurred in our population, with one to four linked copies present. Additionally, in rare instances, the Ppd-B1 gene was absent (a null allele). The one-copy allele, which we labelled Ppd-B1b, and the three-copy allele, which we labelled Ppd-B1a, occurred through a century of wheat breeding, and are still frequent. With several distinct progenitors, the one-copy allele might not be homogenous. The two-copy allele, which we labelled Ppd-B1d, was generally introduced from WW15 (syn. Anza), and the four-copy allele, which we labelled Ppd-B1c, came from Chinese Spring. In paired comparisons, Ppd-B1a and Ppd-B1c reduced days to heading, but Ppd-B1d increased days to heading. Ppd-D1a, with a promoter deletion, Ppd-D1d, with a deletion in Exon 7, and Ppd-D1b, the intact allele, were frequent in modern Australian germplasm. Differences between Ppd-D1a and Ppd-D1d for days to heading under our field conditions depended on alleles of the vernalisation genes, confirming our previous report of large epistatic interactions between these classes of genes. The Ppd-D1b allele conferred a photoperiod response that might be useful for developing cultivars with closer to optimal heading dates from variable sowing dates. Inclusion of Ppd-B1 genotypes, and more precise resolution of Ppd-D1, increased the proportion of the genotypic variance attributed to these vernalisation and photoperiod genes to ~53%.
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Sentinelli, Federica, Ilenia Minicocci, Anna Montali, Luisa Nanni, Stefano Romeo, Michela Incani, M. Gisella Cavallo, Andrea Lenzi, Marcello Arca, and Marco G. Baroni. "Association of RXR-Gamma Gene Variants with Familial Combined Hyperlipidemia: Genotype and Haplotype Analysis." Journal of Lipids 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/517943.
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Background. Familial combined hyperlipidemia (FCHL), the most common genetic form of hyperlipdemia, is characterized by a strong familial clustering and by premature coronary heart disease. The FCHL locus has been mapped to human chromosome 1q21-q23. This region includes the retinoid X receptor gamma (RXRG), a nuclear factor member of the RXR superfamily, which plays important roles in lipid homeostasis.Objective. To investigate the possible role of the RXRG gene in the genetic susceptibility to FCHL.Methods. Variations in RXRG gene were searched by direct sequencing, and the identified SNPs were genotyped by PCR-RFLP in 192 FCHL individuals from 74 families and in 119 controls.Results. We identified 5 polymorphisms in the RXRG gene (rs1128977, rs2651860, rs2134095, rs283696, and rs10918169). Genotyping showed that the A-allele of rs283696 SNP was significantly associated with FCHL (correctedP,Pc<0.01). Also the alleles of the rs10918169 and of the rs2651860 SNP were more frequent in FCHL subjects compared to those in controls, although not significantly after correction. When the clinical characteristics of the FCHL subjects were stratified by allele carrier status for each SNP, the rs2651860 SNP was significantly associated with increased levels of LDL-cholesterol and of Apo-B in T-allele carriers(P<0.04). Finally, haplotypes analysis with all 5 SNPs confirmed the significant association of RXRG gene with FCHL. Specifically, the haplotype containing all 3 “at-risk” alleles, significantly associated with FCHL (A-allele of rs283696, G-allele of rs10918169, and T-allele of rs2651860), showed an OR (Odds Ratio) of 2.02,Pc<0.048. Conversely, the haplotype without all these 3 alleles was associated with a reduced risk for FCHL (OR=0.39,Pc<0.023). The “at-risk” haplotype CTTAG was also associated with higher LDL-C(P<0.015). In conclusion, variation in the RXRG gene may contribute to the genetic dyslipidemia in FCHL subjects.
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Aung, Fleur M., Benjamin Litchtiger, and Issa Khouri. "Comparison of HLA Alleles in Follicular Lymphoma and Chronic Lymphocytic Leukemia Patients Referred for Allogeneic Stem Cell Transplantation." Blood 120, no. 21 (November 16, 2012): 4218. http://dx.doi.org/10.1182/blood.v120.21.4218.4218.
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Abstract Abstract 4218 Introduction: Data recently published showed that besides the several well-known parameters, long term outcome after allogeneic stem cell transplantation (SCT) in chronic lymphocytic leukemia (CLL) may be influenced by the presence or absence of certain HLA class I alleles (HLA-A1+/A2-/B44-) (Khouri et. Al. Cancer 2011). We have also recently published an 11-year progression free survival (PFS) rate of 72% in relapsed follicular lymphoma (FL) after SCT (Khouri et al. Blood 2012). A higher relapse rate has been observed in CLL patients when compared to FL (50% vs. 4%). Since HLA subtypes played an important role in CLL, our goal in this study was to assess and compare over expressed HLA alleles in FL and CLL patients who received a SCT at our center. Methods: Two cohorts of patients who received SCT were retrospectively studied. Group I consisted of 59 Caucasian patients (23 [39%] F: 36 [61%] M) with FL and Group II consisted of 119 Caucasian patients (27 [23%] F: 112 [77%] M) with CLL. The HLA alleles at HLA-A, -B,-C and -DRB1 loci of both groups were analyzed and the HLA typing was performed by polymerase chain reaction (PCR) amplification and oligonucleotide hybridization using commercial kits from Invitrogen (Carlsbad, Ca) or One Lambda (Canoga Park, Ca) that resulted in intermediate resolution. Patients were also typed for these loci using high-resolution methods with PCR amplification and nucleotide sequencing (Abbott, Abbott Park, Ill). The antigen frequencies of all of the alleles of HLA-A, -B,-C AND DRB1 were calculated. Antigen frequency was defined as the percentage of the population possessing the antigen. Antigen frequency comparisons were only done for North American whites due to sample size and control group constraints. The control group was based on a sample analysis of 643 normal North American Whites. The Pearson x2goodness-of-fit test was used to validate the Hardy-Weinberg genetic equilibrium for phenotypic data. The association of various alleles with the control group was determined by using a chi-square test with Yates correction in a 2 × 2 table with 1 degree of freedom (SAS software, version 6.12, SAS Institute Inc, Cary NC). P values < 0.05 at the 95% confidence interval (95% CI) were considered significant. Results: A male predominance was noted in both patient groups. A total of 17 HLA-A, 29 HLA-B, 13 HLA-C and 13 HLA-DRB1 distinct alleles for FL patients and 16 HLA-A, 24 HLA-B, 13 HLA-C and 11 HLA-DRB1 distinct alleles were identified for the CLL patients. Since the predominant ethnic type in both groups were North American Whites, statistically valid comparisons of HLA antigen frequencies were only possible in this population. The observed heterozygosity for FL/CLL patients was 0.93220./0.831932 for HLA-A, 0.915254/0.949579 for HLA-B, 0.779661/0.882352 for HLA-C and 0.847457/0.941176 for HLA-DRB1. There were no untyped patients and all of the patients underwent hematopoietic stem cell transplantation. Our analysis reveals an over expression of HLA-A*03, HLA-C*04, HLA-DRB1*01, HLA-DRB1*07 and HLA-DRB1*15 with frequencies of 25.4%, 24.1%, 22.9%, 28.8% and 8.5 % in FL patients which was significantly higher than the frequencies of 15.1% for HLA-A*03 (p value 0.005), 1.1% for HLA-C*04 (p value < .00001), 10.3% for HLA-DRB1*01 (p value <.0001), 14.4% for HLA-DRB1*07 (p value < .0001) and 15.7% for HLA-DRB1*15 (p value < .0495) in the normal population showing for the first time an over representation of these alleles in patients with FL. In the CLL group our analysis revealed a 24.8% (p value 0.0014) frequency for HLA-A*01 which was significantly higher than the frequency of 16% (p value 0.0014) in the normal population showing an overrepresentation of this allele. The underrepresented allele was HLA-B*38 with a frequency of 3.4% compared to 12.4% (p value 0.0335) in the normal population. When the two groups FL and CLL patients were analyzed, the significant alleles were HLA-A*01, HLA-A*03, HLA-C*04, HLA-DRB1*01 and HLA-DRB1*07. Conclusion: Our results demonstrate a significant difference in HLA expression in Follicular Lymphoma and Chronic Lymphocytic Leukemia patients with the over representation of HLA-A*03, HLA-C*04, HLA-DRB1*01, HLA-DRB1*07 and HLA-DRB1*15 alleles in FL and HLA-A*01 and HLA-B*38 alleles in CLL. We do not know whether these variances account for a different graft-versus-malignancy susceptibility to donor cells between the two groups and this remains to be studied. Disclosures: No relevant conflicts of interest to declare.