Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence
| ISSN: | 0964-6906 |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d40aab35137156feeac5df51720f8c7b https://pubmed.ncbi.nlm.nih.gov/11092766 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....d40aab35137156feeac5df51720f8c7b |
| Autor: | Klaus Rohde, Birgit Wendel, Karla Köpke, George M. Church, Kenneth K. Kidd, Christina Flachmeier, Margret R. Hoehe, Wade H. Berrettini |
| Rok vydání: | 2000 |
| Předmět: |
Adult
Candidate gene Heterozygote Substance-Related Disorders Receptors Opioid mu Black People Biology Polymerase Chain Reaction Genetic variation Genetics Humans Genetic Predisposition to Disease Molecular Biology Gene Genetics (clinical) Phylogeny Sequence (medicine) Polymorphism Genetic Haplotype Nucleic acid sequence Genetic Variation General Medicine Sequence Analysis DNA Black or African American Phenotype Haplotypes Candidate Disease Gene Candidate Gene Analysis |
| Zdroj: | Human molecular genetics. 9(19) |
| ISSN: | 0964-6906 |
| Popis: | To analyze candidate genes and establish complex genotype-phenotype relationships against a background of high natural genome sequence variability, we have developed approaches to (i) compare candidate gene sequence information in multiple individuals; (ii) predict haplotypes from numerous variants; and (iii) classify haplotypes and identify specific sequence variants, or combinations of variants (pattern), associated with the phenotype. Using the human mu opioid receptor gene (OPRM1) as a model system, we have combined these approaches to test a potential role of OPRM1 in substance (heroin/cocaine) dependence. All known functionally relevant regions of this prime candidate gene were analyzed by multiplex sequence comparison in 250 cases and controls; 43 variants were identified and 52 different haplotypes predicted in the subgroup of 172 African-Americans. These haplotypes were classified by similarity clustering into two functionally related categories, one of which was significantly more frequent in substance-dependent individuals. Common to this category was a characteristic pattern of sequence variants [-1793T-->A, -1699Tins, -1320A-->G, -111C-->T, +17C-->T (A6V)], which was associated with substance dependence. This study provides an example of approaches that have been successfully applied to the establishment of complex genotype-phenotype relationships in the presence of abundant DNA sequence variation. |
| Databáze: | OpenAIRE |
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