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

Nat Genet. 2012 Jul 1;44(8):881-5. doi: 10.1038/ng.2334.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group / genetics
  • Base Sequence
  • Chromosome Inversion
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA / genetics
  • DNA Copy Number Variations
  • European Continental Ancestry Group / genetics
  • Evolution, Molecular
  • Female
  • Gene Duplication
  • Gene Frequency
  • Genetics, Population
  • Haplotypes
  • Humans
  • Nuclear Proteins / genetics
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide

Substances

  • NSL1 protein, human
  • Nuclear Proteins
  • DNA