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

Heterogeneity in extent of linkage disequilibrium amongst exonic, intronic, non-coding RNA and intergenic chromosome regions
Heterogeneity in extent of linkage disequilibrium amongst exonic, intronic, non-coding RNA and intergenic chromosome regions
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.
1018-4813
1436-1444
Vergara Lope Gracia, Norma, Alejandra
84ea3389-86d8-4b89-ad65-729173419305
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Vergara Lope Gracia, Norma, Alejandra
84ea3389-86d8-4b89-ad65-729173419305
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64

Vergara Lope Gracia, Norma, Alejandra, Ennis, Sarah, Vorechovsky, Igor, Pengelly, Reuben and Collins, Andrew (2019) Heterogeneity in extent of linkage disequilibrium amongst exonic, intronic, non-coding RNA and intergenic chromosome regions. European Journal of Human Genetics, 27 (9), 1436-1444. (doi:10.1038/s41431-019-0419-0).

Record type: Article

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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Accepted/In Press date: 16 April 2019
e-pub ahead of print date: 3 May 2019
Published date: 2019

Identifiers

Local EPrints ID: 431069
URI: http://eprints.soton.ac.uk/id/eprint/431069
ISSN: 1018-4813
PURE UUID: 64de09a3-db21-42b1-8645-51a4bf706f2f
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Reuben Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771

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Date deposited: 22 May 2019 16:30
Last modified: 09 Jan 2022 05:11

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Contributors

Author: Norma, Alejandra Vergara Lope Gracia
Author: Sarah Ennis ORCID iD
Author: Reuben Pengelly ORCID iD
Author: Andrew Collins ORCID iD

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