Structural haplotypes and recent evolution of the human 17q21.31 region.

Nat Genet
Authors
Keywords
Abstract

Structurally complex genomic regions are not yet well understood. One such locus, human chromosome 17q21.31, contains a megabase-long inversion polymorphism, many uncharacterized copy-number variations (CNVs) and markers that associate with female fertility, female meiotic recombination and neurological disease. Additionally, the inverted H2 form of 17q21.31 seems to be positively selected in Europeans. We developed a population genetics approach to analyze complex genome structures and identified nine segregating structural forms of 17q21.31. Both the H1 and H2 forms of the 17q21.31 inversion polymorphism contain independently derived, partial duplications of the KANSL1 gene; these duplications, which produce novel KANSL1 transcripts, have both recently risen to high allele frequencies (26% and 19%) in Europeans. An older H2 form lacking such a duplication is present at low frequency in European and central African hunter-gatherer populations. We further show that complex genome structures can be analyzed by imputation from SNPs.

Year of Publication
2012
Journal
Nat Genet
Volume
44
Issue
8
Pages
881-5
Date Published
2012 Jul 01
ISSN
1546-1718
URL
DOI
10.1038/ng.2334
PubMed ID
22751096
PubMed Central ID
PMC4020351
Links
Grant list
U01 HG005208 / HG / NHGRI NIH HHS / United States