Abstract
Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical parameters for mapping by linkage and association, and their patterns in Caenorhabditis elegans are poorly understood. We performed high-density SNP genotyping on a large panel of recombinant inbred advanced intercross lines (RIAILs) of C. elegans to characterize the landscape of recombination and, on a panel of wild strains, to characterize population genomic patterns. We confirmed that C. elegans autosomes exhibit discrete domains of nearly constant recombination rate, and we show, for the first time, that the pattern holds for the X chromosome as well. The terminal domains of each chromosome, spanning about 7% of the genome, exhibit effectively no recombination. The RIAILs exhibit a 5.3-fold expansion of the genetic map. With median marker spacing of 61 kb, they are a powerful resource for mapping quantitative trait loci in C. elegans. Among 125 wild isolates, we identified only 41 distinct haplotypes. The patterns of genotypic similarity suggest that some presumed wild strains are laboratory contaminants. The Hawaiian strain, CB4856, exhibits genetic isolation from the remainder of the global population, whose members exhibit ample evidence of intercrossing and recombining. The population effective recombination rate, estimated from the pattern of linkage disequilibrium, is correlated with the estimated meiotic recombination rate, but its magnitude implies that the effective rate of outcrossing is extremely low, corroborating reports of selection against recombinant genotypes. Despite the low population, effective recombination rate and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of genomic similarity, permit association mapping in wild C. elegans strains.
Highlights
The allelic variants that underlie heritable phenotypic variation are distributed along chromosomes
The recombinant inbred advanced intercross lines (RIAILs) contain 3,629 breakpoints in 772 marker intervals; some breakpoints may be identical by descent because of the shared ancestry during the intercrossing phase of RIAIL construction
To assess the utility of C. elegans for association mapping, we explored the correlations between the 907 non-singleton SNPs in out dataset that are not missing any data and two traits, copulatory plugging and epistatic embryonic lethality, that we have phenotyped in the wild isolates and whose underlying causative variants are known [40,41]
Summary
The allelic variants that underlie heritable phenotypic variation are distributed along chromosomes. Their distribution is shaped by the machinery of meiosis within individuals and by mutation, selection, and drift among them. To discover the genetic basis of complex traits, and to understand the evolutionary dynamics that shape this genetic architecture, we must characterize empirical patterns of linkage and linkage disequilibrium. We have undertaken this task in the nematode C. elegans. Because recombination patterns have been studied only on broad scales in individual crosses, involving fewer than two dozen markers per chromosome, dense characterization of a massive cross promises to clarify the recombinational landscape
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