Dataset Information

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

ABSTRACT: N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.

SUBMITTER: Fuselli S

PROVIDER: S-EPMC3099416 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

Fuselli S S Gilman R H RH Chanock S J SJ Bonatto S L SL De Stefano G G Evans C A CA Labuda D D Luiselli D D Salzano F M FM Soto G G Vallejo G G Sajantila A A Pettener D D Tarazona-Santos E E

The pharmacogenomics journal 20060718 2

N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharma ...[more]

PMID: 16847467

Similar Datasets

Project description:BACKGROUND: Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Previous and recent studies have suggested a diversification of type 1 HCV in the South American region. The degree of genetic variation among HCV strains circulating in Bolivia and Colombia is currently unknown. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' non-coding region (5'NCR) sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America. METHODS: Phylogenetic tree analysis was performed using the neighbor-joining method under a matrix of genetic distances established under the Kimura-two parameter model. Signature pattern analysis, which identifies particular sites in nucleic acid alignments of variable sequences that are distinctly representative relative to a background set, was performed using the method of Korber & Myers, as implemented in the VESPA program. Prediction of RNA secondary structures was done by the method of Zuker & Turner, as implemented in the mfold program. RESULTS: Phylogenetic tree analysis of HCV strains isolated in the South American region revealed the presence of a distinct genetic lineage inside genotype 1. Signature pattern analysis revealed that the presence of this lineage is consistent with the presence of a sequence signature in the 5'NCR of HCV strains isolated in South America. Comparisons of these results with the ones found for Europe or North America revealed that this sequence signature is characteristic of the South American region. CONCLUSION: Phylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct type 1 sub-population. The coexistence of distinct type 1 HCV subpopulations is consistent with quasispecies dynamics, and suggests that multiple coexisting subpopulations may allow the virus to adapt to its human host populations.

Project description:BackgroundThroughout the world, harvesting of mussels Mytilus spp. is based on the exploitation of natural populations and aquaculture. Aquaculture activities include transfers of spat and live adult mussels between various geographic locations, which may result in large-scale changes in the world distribution of Mytilus taxa. Mytilus taxa are morphologically similar and difficult to distinguish. In spite of much research on taxonomy, evolution and geographic distribution, the native Mytilus taxa of the Southern Hemisphere are poorly understood. Recently, single nucleotide polymorphisms (SNPs) have been used to clarify the taxonomic status of populations of smooth shelled mussels from the Pacific coast of South America. In this paper, we used a set of SNPs to characterize, for the first time, populations of smooth shelled mussels Mytilus from the Atlantic coast of South America.ResultsMytilus spp. samples were collected from eastern South America. Six reference samples from the Northern Hemisphere were used: Mytilus edulis from USA and Northern Ireland, Mytilus trossulus from Canada, and Mytilus galloprovincialis from Spain and Italy. Two other reference samples from the Southern Hemisphere were included: M. galloprovincialis from New Zealand and Mytilus chilensis from Chile. Fifty-five SNPs were successfully genotyped, of which 51 were polymorphic. Population genetic analyses using the STRUCTURE program revealed the clustering of eight populations from Argentina (Mytilus platensis) and the clustering of the sample from Ushuaia with M. chilensis from Chile. All individuals in the Puerto Madryn (Argentina) sample were identified as M. platensis × M. galloprovincialis F2 (88.89%) hybrids, except one that was classified as Mediterranean M. galloprovincialis. No F1 hybrids were observed.ConclusionsWe demonstrate that M. platensis (or Mytilus edulis platensis) and M. chilensis are distinct native taxa in South America, which indicates that the evolutionary histories of Mytilus taxa along the Atlantic and Pacific coasts differ. M. platensis is endangered by hybridization with M. galloprovincialis that was introduced from Europe into the Puerto Madryn area in Argentina, presumably by accidental introduction via ship traffic. We confirm the occurrence of a native M. chilensis population in southern Argentina on the coast of Patagonia.

Dataset Information

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

Publications

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets