Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach
<p>Abstract</p> <p>Background</p> <p>Numerous studies have attempted to relate genetic polymorphisms within the N-acetyltransferase 2 gene (<it>NAT2</it>) to interindividual differences in response to drugs or in disease susceptibility. However, genotyping o...
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| Format: | Article |
| Language: | English |
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BMC
2005-06-01
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| Series: | BMC Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2156/6/30 |
| _version_ | 1818229787337949184 |
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| author | Sabbagh Audrey Darlu Pierre |
| author_facet | Sabbagh Audrey Darlu Pierre |
| author_sort | Sabbagh Audrey |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Numerous studies have attempted to relate genetic polymorphisms within the N-acetyltransferase 2 gene (<it>NAT2</it>) to interindividual differences in response to drugs or in disease susceptibility. However, genotyping of individuals single-nucleotide polymorphisms (SNPs) alone may not always provide enough information to reach these goals. It is important to link SNPs in terms of haplotypes which carry more information about the genotype-phenotype relationship. Special analytical techniques have been designed to unequivocally determine the allocation of mutations to either DNA strand. However, molecular haplotyping methods are labour-intensive and expensive and do not appear to be good candidates for routine clinical applications. A cheap and relatively straightforward alternative is the use of computational algorithms. The objective of this study was to assess the performance of the computational approach in <it>NAT2 </it>haplotype reconstruction from phase-unknown genotype data, for population samples of various ethnic origin.</p> <p>Results</p> <p>We empirically evaluated the effectiveness of four haplotyping algorithms in predicting haplotype phases at <it>NAT2</it>, by comparing the results with those directly obtained through molecular haplotyping. All computational methods provided remarkably accurate and reliable estimates for <it>NAT2 </it>haplotype frequencies and individual haplotype phases. The Bayesian algorithm implemented in the PHASE program performed the best.</p> <p>Conclusion</p> <p>This investigation provides a solid basis for the confident and rational use of computational methods which appear to be a good alternative to infer haplotype phases in the particular case of the <it>NAT2 </it>gene, where there is near complete linkage disequilibrium between polymorphic markers.</p> |
| first_indexed | 2024-12-12T10:24:09Z |
| format | Article |
| id | doaj.art-62862701c0bb48cc9af046deb3394d68 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-12-12T10:24:09Z |
| publishDate | 2005-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genetics |
| spelling | doaj.art-62862701c0bb48cc9af046deb3394d682022-12-22T00:27:30ZengBMCBMC Genetics1471-21562005-06-01613010.1186/1471-2156-6-30Inferring haplotypes at the <it>NAT2 </it>locus: the computational approachSabbagh AudreyDarlu Pierre<p>Abstract</p> <p>Background</p> <p>Numerous studies have attempted to relate genetic polymorphisms within the N-acetyltransferase 2 gene (<it>NAT2</it>) to interindividual differences in response to drugs or in disease susceptibility. However, genotyping of individuals single-nucleotide polymorphisms (SNPs) alone may not always provide enough information to reach these goals. It is important to link SNPs in terms of haplotypes which carry more information about the genotype-phenotype relationship. Special analytical techniques have been designed to unequivocally determine the allocation of mutations to either DNA strand. However, molecular haplotyping methods are labour-intensive and expensive and do not appear to be good candidates for routine clinical applications. A cheap and relatively straightforward alternative is the use of computational algorithms. The objective of this study was to assess the performance of the computational approach in <it>NAT2 </it>haplotype reconstruction from phase-unknown genotype data, for population samples of various ethnic origin.</p> <p>Results</p> <p>We empirically evaluated the effectiveness of four haplotyping algorithms in predicting haplotype phases at <it>NAT2</it>, by comparing the results with those directly obtained through molecular haplotyping. All computational methods provided remarkably accurate and reliable estimates for <it>NAT2 </it>haplotype frequencies and individual haplotype phases. The Bayesian algorithm implemented in the PHASE program performed the best.</p> <p>Conclusion</p> <p>This investigation provides a solid basis for the confident and rational use of computational methods which appear to be a good alternative to infer haplotype phases in the particular case of the <it>NAT2 </it>gene, where there is near complete linkage disequilibrium between polymorphic markers.</p>http://www.biomedcentral.com/1471-2156/6/30 |
| spellingShingle | Sabbagh Audrey Darlu Pierre Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach BMC Genetics |
| title | Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach |
| title_full | Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach |
| title_fullStr | Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach |
| title_full_unstemmed | Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach |
| title_short | Inferring haplotypes at the <it>NAT2 </it>locus: the computational approach |
| title_sort | inferring haplotypes at the it nat2 it locus the computational approach |
| url | http://www.biomedcentral.com/1471-2156/6/30 |
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