A Simple Model of Linkage Disequilibrium and Genetic Drift in Human Genomic SNPs: Importance of Demography and SNP Age

2005 ◽  
Vol 60 (4) ◽  
pp. 181-195 ◽  
Author(s):  
Joanna Polanska ◽  
Marek Kimmel
Keyword(s):  
Linkage Disequilibrium ◽  
Simple Model ◽  
Genetic Drift ◽  
Human Genomic

scholarly journals Linkage disequilibrium in experimental populations of Drosophila simulans: a test of the random drift hypothesis

1987 ◽  
Vol 50 (3) ◽  
pp. 187-193
Author(s):  
Catherine Montchamp-Moreau ◽  
Mariano Katz
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Drift ◽  
Natural Populations ◽  
Aldehyde Oxidase ◽  
Drosophila Simulans ◽  
Random Drift ◽  
Esterase 6 ◽  
Experimental Populations ◽  
Experimental Values ◽  
Neutralist Hypothesis

SummaryLinkage disequilibrium between five polymorphic enzymic loci of the third chromosome (Esterase-6, Phosphoglucomutase, Esterase-C, Aldehyde Oxidase and Acid Phosphatase) was studied in experimental populations of Drosophila simulans. Gametic data were obtained by mating sampled males with homozygous females at the five loci. Four cage populations were initiated with flies caught from natural populations. Extensive linkage disequilibrium was detected after 25 or 34 generations. The effective size of these populations was estimated about 400. Monte-Carlo simulations were performed in order to determine whether the observed disequilibria could be due to genetic drift. The observed probability distribution of the experimental values of r (the gametic correlation coefficient) was consistent with the distribution expected under random genetic drift. Our results are thus in accordance with the neutralist hypothesis.

scholarly journals A theoretical analysis of linkage disequilibrium produced by genetic drift in Drosophila populations

1986 ◽  
Vol 48 (3) ◽  
pp. 161-166 ◽  
Author(s):  
Catherine Montchamp-Moreau ◽  
Mariano Katz
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Drift ◽  
Statistical Tests ◽  
Burst Size ◽  
Natural Populations ◽  
Finite Size ◽  
Gene Frequencies ◽  
Accurate Knowledge ◽  
Maximum Value ◽  
Cyclical Fluctuations

SummaryWe analyse the progression of linkage disequilibrium produced by random genetic drift in populations subject to cyclical fluctuations in size. Our model is applied to natural populations of Drosophila which show an annual demographic cycle of bottleneck (finite size) and demographic burst (size supposed to be infinite). In these populations, linkage disequilibrium stabilizes in such a way that, at equilibrium, the expected square of the correlation of gene frequencies E(r2) shows a stable cycle from year to year. If two loci are tightly linked, E(r2) barely varies during the annual cycle. Its values remain close to the value expected in a population of the same but constant effective size. If two loci are loosely linked, fluctuations in E(r2) are large. The maximum value, reached at the end of the bottleneck, is 10 to 100 times greater than the value obtained at the end of the burst. Our results show that the interpretation of observed linkage disequilibrium, by means of statistical tests, requires an accurate knowledge of population demography.

scholarly journals Uncorrelated genetic drift of gene frequencies and linkage disequilibrium in some models of linked overdominant polymorphisms

1974 ◽  
Vol 24 (3) ◽  
pp. 281-294 ◽  
Author(s):  
Joseph Felsenstein
Keyword(s):  
Linkage Disequilibrium ◽  
Covariance Matrix ◽  
Genetic Drift ◽  
Conditional Distribution ◽  
Large Population ◽  
Multivariate Normal ◽  
Gene Frequencies ◽  
Constant Variance ◽  
Population Sizes ◽  
Multiplicative Family

SUMMARYFor large population sizes, gene frequencies p and q at two linked over-dominant loci and the linkage disequilibrium parameter D will remain close to their equilibrium values. We can treat selection and recombination as approximately linear forces on p, q and D, and we can treat genetic drift as a multivariate normal perturbation with constant variance-covariance matrix. For the additive-multiplicative family of two-locus models, p, q and D are shown to be (approximately) uncorrelated. Expressions for their variances are obtained. When selection coefficients are small the variances of p and q are those previously given by Robertson for a single locus. For small recombination fractions the variance of D is that obtained for neutral loci by Ohta & Kimura. For larger recombination fractions the result differs from theirs, so that for unlinked loci r2 ≃ 2/(3N) instead of 1/(2N). For the Lewontin-Kojima and Bodmer symmetric viability models, and for a model symmetric at only one of the loci, a more exact argument is possible. In the asymptotic conditional distribution in these cases, various of p, q and D are uncorrelated, depending on the type of symmetiy in the model.

scholarly journals Linkage disequilibrium under polysomic inheritance

2020 ◽  
Author(s):  
Kang Huang ◽  
Derek W. Dunn ◽  
Wenkai Li ◽  
Dan Wang ◽  
Baoguo Li
Keyword(s):  
Linkage Disequilibrium ◽  
Equilibrium State ◽  
Genetic Drift ◽  
Recombination Rate ◽  
Mating Systems ◽  
Correlation Coefficients ◽  
Effective Population ◽  
Under Five ◽  
Polysomic Inheritance ◽  
Linkage Disequilibrium Measure

AbstractThe influence of genetic drift on linkage disequilibrium in finite populations has been extensively studied in diploids. However, to date the effects of ploidy on LD has not been extensively studied. We here extend the linkage disequilibrium measure D and Burrow’s Δ statistic to include polysomic inheritance, as well as their corresponding squared correlation coefficients r2 and , where the former is for phased genotypes and the latter for unphased genotypes. Weir & Hill’s double non-identity framework is also extended to include polysomic inheritance, and the expressions of double non-identity coefficients are derived under five mating systems. On this basis, the approximated expectations of estimated r2 and at equilibrium state, d2 and δ2, are derived under five mating systems. We assess the behaviors of the estimated r2 and and the influence of the recombination rate on d2 or δ2, simulate the application of estimating effective population size, and evaluate the statistical performance of the method of estimating.

scholarly journals Linkage disequilibrium between rare mutations

Genetics ◽  
2022 ◽  
Author(s):  
Benjamin H Good
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Drift ◽  
Deleterious Mutations ◽  
Fitness Costs ◽  
Theoretical Understanding ◽  
Evolutionary Forces ◽  
Frequency Scale ◽  
Rare Mutations ◽  
Site Frequency Spectrum ◽  
Analytical Expressions

Abstract The statistical associations between mutations, collectively known as linkage disequilibrium (LD), encode important information about the evolutionary forces acting within a population. Yet in contrast to single-site analogues like the site frequency spectrum, our theoretical understanding of linkage disequilibrium remains limited. In particular, little is currently known about how mutations with different ages and fitness costs contribute to expected patterns of LD, even in simple settings where recombination and genetic drift are the major evolutionary forces. Here, I introduce a forward-time framework for predicting linkage disequilibrium between pairs of neutral and deleterious mutations as a function of their present-day frequencies. I show that the dynamics of linkage disequilibrium become much simpler in the limit that mutations are rare, where they admit a simple heuristic picture based on the trajectories of the underlying lineages. I use this approach to derive analytical expressions for a family of frequency-weighted LD statistics as a function of the recombination rate, the frequency scale, and the additive and epistatic fitness costs of the mutations. I find that the frequency scale can have a dramatic impact on the shapes of the resulting LD curves, reflecting the broad range of time scales over which these correlations arise. I also show that the differences between neutral and deleterious LD are not purely driven by differences in their mutation frequencies, and can instead display qualitative features that are reminiscent of epistasis. I conclude by discussing the implications of these results for recent LD measurements in bacteria. This forward-time approach may provide a useful framework for predicting linkage disequilibrium across a range of evolutionary scenarios.

scholarly journals Estimating the rates of crossover and gene conversion from individual genomes

2021 ◽  
Author(s):  
Derek Setter ◽  
Sam Ebdon ◽  
Ben Jackson ◽  
Konrad Lohse
Keyword(s):  
Linkage Disequilibrium ◽  
Simple Model ◽  
Gene Conversion ◽  
House Mouse ◽  
Mus Musculus ◽  
Population Genetic ◽  
Composite Likelihood ◽  
Or Gene ◽  
Evolutionary Consequences ◽  
Dependent Probability

Recombination can occur either as a result of crossover or gene conversion events. Population genetic methods for inferring the rate of recombination from patterns of linkage disequilibrium generally assume a simple model of recombination that only involves crossover events and ignore gene conversion. However, distinguishing the two processes is not only necessary for a complete description of recombination, but also essential for understanding the evolutionary consequences of inversions and other genomic partitions in which crossover (but not gene conversion) is reduced. We present heRho, a simple composite likelihood scheme for co-estimating the rate of crossover and gene conversion from individual diploid genomes. The method is based on analytic results for the distance-dependent probability of heterozygous and homozygous states at two loci. We apply heRho to simulations and data from the house mouse Mus musculus castaneus, a well studied model. Our analyses show i) that the rates of crossover and gene conversion can be accurately co-estimated at the level of individual chromosomes and ii) that previous estimates of the population scaled rate of recombination ρ = 4Ner under a pure crossover model are likely biased

Disequilibrium Pattern Analysis. I. Theory

Genetics ◽  
1987 ◽  
Vol 116 (4) ◽  
pp. 623-632
Author(s):  
Glenys Thomson ◽  
William Klitz
Keyword(s):  
Linkage Disequilibrium ◽  
Dna Sequencing ◽  
Genetic Drift ◽  
Pattern Analysis ◽  
Population Data ◽  
Distinct Pattern ◽  
Random Genetic Drift ◽  
A Value ◽  
Selection Event ◽  
Entire Array

ABSTRACT We have developed a method, disequilibrium pattern analysis, for examining the disequilibrium distribution of the entire array of two locus multiallelic haplotypes in a population. It is shown that a selected haplotype will produce a distinct pattern of linkage disequilibrium values for all generations while the selection is acting. This pattern will also presumably be maintained for many generations after the selection event, until the disequilibrium pattern is eventually broken down by genetic drift and recombination. Related haplotypes, sharing an allele with a selected haplotype, assume a value of linkage disequilibrium proportional to the frequency of the unshared allele and have a single negative value of the normalized linkage disequilibrium. The analysis assumes zero linkage disequilibrium for all allelic combinations initially. The same basic results continue to apply if the selection involves a new mutant, the occurrence of which creates linkage disequilibrium for some haplotypes. The disequilibrium pattern predicted under selection is robust with respect to the influence of migration and random genetic drift. This method is applicable to population data having linked polymorphic loci including that determined from protein or DNA sequencing.

scholarly journals Linkage disequilibrium and genetic variability

1974 ◽  
Vol 23 (3) ◽  
pp. 281-289 ◽  
Author(s):  
M. G. Bulmer
Keyword(s):  
Linkage Disequilibrium ◽  
Simple Model ◽  
Genetic Variability ◽  
Computer Simulations ◽  
Genetic Variance ◽  
Recombination Fraction ◽  
Harmonic Mean ◽  
Exact Results ◽  
Appreciable Change ◽  
Chromosome Maps

SUMMARYIt has been shown previously that, even in the absence of linkage, selection can cause an appreciable change in the genetic variance of a metric character due to disequilibrium; this change is temporary and is rapidly reversed when selection ceases. This result is here extended to allow for the effect of linkage, and it is shown that the change in the variance is effectively determined by the harmonic mean of the recombination fractions. The validity of the approximate general formula derived here has been checked by comparison with exact results obtained from models with five or six loci. In order to determine the likely value of the harmonic mean recombination fraction, a simple model was constructed in which it was assumed that loci are distributed at random along the chromosome maps. Results of computer simulations of this model are reported for different chromosome numbers and numbers of loci.

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