Molecular and population analysis of natural selection on the human haptoglobin duplication

Rodriguez, Santiago, Williams, Dylan M., Guthrie, Philip A. I., Mcardle, Wendy L., Smith, George Davey, Evans, David M., Gaunt, Tom R. and Day, Ian N. M. (2012) Molecular and population analysis of natural selection on the human haptoglobin duplication. Annals of Human Genetics, 76 5: 352-362. doi:10.1111/j.1469-1809.2012.00716.x

Author Rodriguez, Santiago
Williams, Dylan M.
Guthrie, Philip A. I.
Mcardle, Wendy L.
Smith, George Davey
Evans, David M.
Gaunt, Tom R.
Day, Ian N. M.
Title Molecular and population analysis of natural selection on the human haptoglobin duplication
Journal name Annals of Human Genetics   Check publisher's open access policy
ISSN 0003-4800
Publication date 2012
Sub-type Article (original research)
DOI 10.1111/j.1469-1809.2012.00716.x
Open Access Status
Volume 76
Issue 5
Start page 352
End page 362
Total pages 11
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell
Language eng
Subject 2716 Genetics (clinical)
1311 Genetics
Abstract Haptoglobin binds free haemoglobin that prevents oxidative damage produced by haemolysis. There is a copy number variant (CNV) in the haptoglobin gene (HP) consisting of two alleles, Hp1 (no duplication), and Hp2 (1.7kb duplication involving two exons). The spread of the Hp2 allele is believed to have taken place under selective pressures conferred by malaria resistance. However, molecular evidence is lacking and Hp did not emerge in genomewide SNPs surveys for evidence of selection. In Europe, there is geographical constancy of Hp2 frequency, indicative of absence of clinal pressures and that modern day European alleles represent a "snapshot" of their out-of-Africa migrations. In this work we test for signatures of natural selection acting on the Hp CNV in a sample from the UK population (Avon Longitudinal Study of Parents and Children, ALSPAC). We present here heterozygosity decay, pairwise FST values observed between ALSPAC and 301 populations from all five populated continents, extended haplotype homozygosity analyses involving the CNV and 80 SNPs surrounding the CNV ∼500kb in each direction, and linkage disequilibrium and pairwise haplotypic analyses involving 160 SNPs on chromosome 16q22.1. Taken together, our results represent the first molecular analysis of natural selection in the Hp CNV genetic region.
Keyword ALSPAC
Copy number variant
Natural selection
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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