Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism

摘要: During the first decade of new millennium, remarkable advances in technology allowed investigators all areas biological research to collect massive amounts genetic data at an unprecedented rate. The genomics revolution, which began with sequencing human genome, was basis for efforts such as 1000 Genomes Project (www.1000genomes. org) that strive compile a comprehensive catalogue variation humans. A across multiple species also borne out this effort. Indeed, genome canonical mouse strain, called C57BL/6, followed by other inbred strains, has opened major opportunities fundamental understanding how organism's makeup (i.e., genotype) is related its observable characteristics phenotype). Sophisticated tools creating genetically engineered animal models diseases have reached point where community-centered begun eclipse previous individual laboratories. These genomic advances, coupled progress genetic-engineering technology, are set significantly enhance disease, including alcoholism. An inherited predisposition alcoholism been suspected hundreds years because observation tends run families. However, familial pattern not direct proof vulnerability, it could be explained shared environment. It until 1970s notion scientifically tested systematic fashion, when Goodwin and colleagues (1973) studied drinking histories 55 adopted-out sons alcoholics 78 nonalcoholics, whom were adopted within 6 weeks life. worth noting study had no knowledge their parents results analysis striking: who nonrelated foster families four times likely become compared nonalcoholics. Similar lines twin family studies convincingly demonstrated factors account between 50 60 percent vulnerability although statistic provides compelling evidence influence on alcoholism, does indicate specific genes increase or decrease risk developing search associated toward more than 25 ago. One concerted map genes, Collaborative Studies Genetics Alcoholism (COGA), established 1989. COGA sample derived from 100 nuclear densely affected extensive genotypic well phenotypic information collected. To date, researchers identified about 20 contribute sample. over world, range different populations, additional variants encode proteins involved almost brain-signaling neurotransmitter) systems, [gamma]-aminobutyric acid (GABA), glutamate, serotonin, dopamine, acetylcholine systems. Genes alcohol metabolism, signaling mechanisms (e.g., neuropeptide neuroendocrine signaling), cellular architecture implicated (Edenberg Foroud 2006; Kranzler Edenberg 2010). Yet, work some candidate only step gaining insight into etiology next understand alters brain function determine most important and, finally, treatment. …