Dataset Information

Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

ABSTRACT: We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ?5. We used r(2) ? 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SNPs is also common when minor allele frequency (MAF) is low: 37% of SNPs with MAF < 0.1 are highly correlated with SNPs more than 100 kb distant. Although SNPs within regions with polymorphic inversions are highly correlated with somewhat larger numbers of SNPs, and these correlated SNPs are on average farther away, the probability that a SNP in such regions is highly correlated with at least one other SNP is very similar to SNPs outside inversions. Previous karyotyping of the DGRP lines has been inconsistent, and we used LD and genotype to investigate these discrepancies. When previous studies agreed on inversion karyotype, our analysis was almost perfectly concordant with those assignments. In discordant cases, and for inversion heterozygotes, our results suggest errors in two previous analyses or discordance between genotype and karyotype. Heterozygosities of chromosome arms are, in many cases, surprisingly highly correlated, suggesting strong epsistatic selection during the inbreeding and maintenance of the DGRP lines.

SUBMITTER: Houle D

PROVIDER: S-EPMC4528326 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

Houle David D Márquez Eladio J EJ

G3 (Bethesda, Md.) 20150610 8

We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r(2) ≥ 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SN ...[more]

PMID: 26068573

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Project description:Whole-genome resequencing of experimental populations evolving under a specific selection regime has become a popular approach to determine genotype-phenotype maps and understand adaptation to new environments. Despite its conceptual appeal and success in identifying some causative genes, it has become apparent that many studies suffer from an excess of candidate loci. Several explanations have been proposed for this phenomenon, but it is clear that information about the linkage structure during such experiments is needed. Until now only Pool-Seq (whole-genome sequencing of pools of individuals) data were available, which do not provide sufficient information about the correlation between linked sites. We address this problem in two complementary analyses of three replicate Drosophila melanogaster populations evolving to a new hot temperature environment for almost 70 generations. In the first analysis, we sequenced 58 haploid genomes from the founder population and evolved flies at generation 67. We show that during the experiment linkage disequilibrium (LD) increased almost uniformly over much greater distances than typically seen in Drosophila. In the second analysis, Pool-Seq time series data of the three replicates were combined with haplotype information from the founder population to follow blocks of initial haplotypes over time. We identified 17 selected haplotype-blocks that started at low frequencies in the base population and increased in frequency during the experiment. The size of these haplotype-blocks ranged from 0.082 to 4.01 Mb. Moreover, between 42% and 46% of the top candidate single nucleotide polymorphisms from the comparison of founder and evolved populations fell into the genomic region covered by the haplotype-blocks. We conclude that LD in such rising haplotype-blocks results in long range hitchhiking over multiple kilobase-sized regions. LD in such haplotype-blocks is therefore a major factor contributing to an excess of candidate loci. Although modifications of the experimental design may help to reduce the hitchhiking effect and allow for more precise mapping of causative variants, we also note that such haplotype-blocks might be well suited to study the dynamics of selected genomic regions during experimental evolution studies.

Dataset Information

Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

Publications

Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

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