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Sub‐Saharan African coding sequence variation and haplotype diversity at the NAT2 gene
Author(s) -
Patin Etienne,
Harmant Christine,
Kidd Ken K.,
Kidd Judith,
Froment Alain,
Mehdi S. Qasim,
Sica Lucas,
Heyer Evelyne,
QuintanaMurci Lluís
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9438
Subject(s) - biology , haplotype , genetics , gene , locus (genetics) , coding region , genetic variation , population , genetic diversity , polymorphism (computer science) , evolutionary biology , allele , demography , sociology
A total of 530 chromosomes from 12 sub‐Saharan African populations were sequenced at the human arylamine N‐acetyltransferase NAT2 gene. We identified seven novel non‐synonymous mutations observed at low frequencies (<11%) in our African multi‐ethnic panel. By using algorithms based on evolutionary conservation, two mutations (c.70T>A [p.L24I] and c.578C>T [p.T193M]) for which the activity of their encoded protein has never been determined, were predicted to entail a potentially damaging effect on protein activity. In addition, approximately 5% of the overall NAT2 African haplotypes presented an unknown functional effect. More interestingly, NAT2 haplotype frequencies and acetylation status inference revealed that the hunter‐gatherer Western Pygmies and !Kung San were mainly composed of fast and intermediate acetylators, in clear contrast with most agriculturalist populations. These observations highlight the need of a detailed genetic characterization of African populations at this locus to adapt medical treatment, such as the antitubercular isoniazid, to individual/population make‐up in the most effective manner. © 2006 Wiley‐Liss, Inc.