title: Sub-Saharan African coding sequence variation and haplotype diversity at the NAT2 gene.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS) FRE 2849, Unit of Molecular Prevention and Therapy of Human Diseases, Institut Pasteur, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.forename: Christine
authors.initials: C
authors.lastname: Harmant
authors.forename: Ken K
authors.initials: KK
authors.lastname: Kidd
authors.forename: Judith
authors.initials: J
authors.lastname: Kidd
authors.forename: Alain
authors.initials: A
authors.lastname: Froment
authors.forename: S Qasim
authors.initials: SQ
authors.lastname: Mehdi
authors.forename: Lucas
authors.initials: L
authors.lastname: Sica
authors.forename: Evelyne
authors.initials: E
authors.lastname: Heyer
authors.forename: Lluís
authors.initials: L
authors.lastname: Quintana-Murci
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005843:Geography; D006239:Haplotypes; D006801:Humans; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human