Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence

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. -->
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:
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