| Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci. | |
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MedLine Citation:
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PMID: 16086309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bitter taste perception in humans is mediated by receptors encoded by 25 genes that together comprise the TAS2R (or T2R) gene family. The ability to identify the ligand(s) for each of these receptors is dependent on understanding allelic variation in TAS2R genes, which may have a significant effect on ligand recognition. To investigate the extent of coding variation among TAS2R alleles, we performed a comprehensive evaluation of sequence and haplotype variation in the human bitter taste receptor gene repertoire. We found that these genes exhibit substantial coding sequence diversity. In a worldwide population sample of 55 individuals, we found an average of 4.2 variant amino acid positions per gene. In aggregate, the 24 genes analyzed here, along with the phenylthiocarbamide (PTC) receptor gene analyzed previously, specify 151 different protein coding haplotypes. Analyses of the ratio of synonymous and nonsynonymous nucleotide substitutions using the Ka/Ks ratio revealed an excess of amino acid substitutions relative to most other genes examined to date (Ka/Ks = 0.94). In addition, comparisons with more than 1,500 other genes revealed that levels of diversity in the TAS2R genes were significantly greater than expected (pi = 0.11%; p < 0.01), as were levels of differentiation among continental populations (FST = 0.22; p < 0.05). These diversity patterns indicate that unusually high levels of allelic variation are found within TAS2R loci and that human populations differ appreciably with respect to TAS2R allele frequencies. Diversity in the TAS2R genes may be accounted for by natural selection, which may have favored alleles responsive to toxic, bitter compounds found in plants. These findings are consistent with the view that different alleles of the TAS2R genes encode receptors that recognize different ligands, and suggest that the haplotypes we have identified will be important in studies of receptor-ligand recognition. |
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Authors:
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Unkyung Kim; Stephen Wooding; Dante Ricci; Lynn B Jorde; Dennis Drayna |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Human mutation Volume: 26 ISSN: 1098-1004 ISO Abbreviation: Hum. Mutat. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-18 Completed Date: 2006-07-28 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9215429 Medline TA: Hum Mutat Country: United States |
Other Details:
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Languages: eng Pagination: 199-204 Citation Subset: IM |
Affiliation:
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Department of Biology, Kyungpook National University, Daegu, Republic of Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Genetic Variation* Haplotypes / genetics* Humans Ligands Polymorphism, Single Nucleotide Receptors, Cell Surface / genetics* Receptors, G-Protein-Coupled Selection, Genetic Sequence Analysis, DNA Taste* Taste Buds / physiology |
| Grant Support | |
ID/Acronym/Agency:
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ES12125/ES/NIEHS NIH HHS; HL070048/HL/NHLBI NIH HHS; Z01-DC000046-04/DC/NIDCD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/taste receptors, type 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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