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High-throughput profiling of sequence variation in a single gene
Association between substance dependence and version of µ opioid receptor gene
  
By
Edward R. Winstead


The euphoria-producing effects of drugs such as morphine are likely to be mediated in the brain by the m opioid receptor protein. The protein is a molecular target of morphine and has been linked in animal studies to cocaine and alcohol, making it a prime suspect for playing a role in the biology of reward, tolerance, and dependence.

The m opioid receptor gene contains a number of variable DNA sequences. A study led by Margret R. Hoehe, of the Max Delbrück Center for Molecular Medicine in Berlin, recently assessed the sequence variation of this gene in a population at risk for substance abuse. Hoehe and colleagues profiled the variable DNA sequences in this gene using blood samples from nearly 250 individuals and found a total of 52 different forms of the gene. An analysis revealed that a form of the gene—a combination of the variants—was associated with substance abuse in the sample population.

"Our results suggest that individuals carrying this characteristic pattern may be at an increased risk of developing substance dependence under certain additional environmental and genetic circumstances," the authors write in a recent issue of Human Molecular Genetics. More than 1.7 million letters of genetic code were analyzed for this study, which was a test case for high-throughput sequencing techniques and analytical tools developed by Hoehe and others.

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Hoehe, M.R. et al. Sequence variability and candidate gene analysis in complex disease: association of m opioid receptor gene variation with substance dependence. Hum Mol Genet 9, 2895-2908 (November 22, 2000).
 

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