Heterogeneity in extent of linkage disequilibrium amongst exonic, intronic, non-coding RNA and intergenic chromosome regions

Abstract

Whole genome sequence data enable construction of high resolution linkage disequilibrium (LD) maps revealing the LD structure of functional elements within genic and sub-genic sequences. The Malecot-Morton model defines LD map distances in linkage disequilibrium units (LDUs), analogous to the centimorgan scale of linkage maps. For whole genome sequence-derived LD maps we introduce the ratio of corresponding map lengths kilobases/LDU to describe the extent of LD within genome components. The extent of LD is highly variable across the genome ranging from ~38 Kb for intergenic sequences to ~858 Kb for centromeric regions. LD is ~16% more extensive in genic, compared to intergenic sequences, reflecting relatively increased selection and/or reduced recombination in genes. The LD profile across 18268 autosomal genes reveals reduced extent of LD, consistent with elevated recombination, in exonic regions near the 5’ end of genes but more extensive LD, compared to intronic sequences, across more centrally located exons. Genes classified as essential and genes linked to Mendelian phenotypes show more extensive LD compared to genes associated with complex traits, perhaps reflecting differences in selective pressure. Significant differences between exonic, intronic and intergenic components demonstrate that fine-scale LD structure provides important insights into genome function which cannot be revealed by LD analysis of much lower resolution array-based genotyping and conventional linkage maps.

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Identifiers

ORCID for Sarah Ennis: orcid.org/0000-0003-2648-0869

ORCID for Igor Vorechovsky: orcid.org/0000-0002-6740-6502

ORCID for Reuben Pengelly: orcid.org/0000-0001-7022-645X

ORCID for Andrew Collins: orcid.org/0000-0001-7108-0771

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