Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3 0 -UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5-CHRNA3-CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA. Molecular Psychiatry (2009) 14, 501-510; doi:10.1038/mp.2008 published online 15 April 2008 Keywords: nicotinic acetylcholine receptors; mRNA expression; alcohol dependence; polymorphism IntroductionIt is well established that alcohol and tobacco use are highly correlated in humans. Current smokers are more likely to drink heavily and to binge drink than those who have never smoked, and alcoholics smoke more heavily and endorse nicotine withdrawal symptoms at a higher rate than nonalcoholics. [1][2][3][4][5] The National Longitudinal Epidemiologic Survey reported that early onset smoking was a significant predictor of lifetime drinking and subsequent progression to lifetime alcohol abuse and dependence. 6 Both alcohol dependence and habitual smoking are transmitted in families and genetic factors contribute to the development of both of these disorders. [7][8][9][10][11][12][13][14] Evidence from electrophysiological, pharmacological and neurochemical studies suggest that ethanol may interact with nicotinic acetylcholine receptors (nAChR). [15][16][17][18] The nAChR gene family has 11 known subunits (a 2 , a 3 , a 4 , a 5 , a 6 , a 7 , a 8 , a 9 and b 2 , b 3 , b 4 ); these subunits form pentameric receptors with different combinations of subunits. 19,20 The effects of ethanol on nAChRs depend on the receptor subunit composition. Studies using different nAChR subtype compositions expressed in Xenopus oocytes demonstrate that ethanol tends to increase nicotine responsiveness in a2b2, a3b2 and a4b2 receptor subtypes, whereas low concentrations of et...

BackgroundCamelina sativa, an oilseed crop in the Brassicaceae family, has inspired renewed interest due to its potential for biofuels applications. Little is understood of the nature of the C. sativa genome, however. A study was undertaken to characterize two genes in the fatty acid biosynthesis pathway, fatty acid desaturase (FAD) 2 and fatty acid elongase (FAE) 1, which revealed unexpected complexity in the C. sativa genome.ResultsIn C. sativa, Southern analysis indicates the presence of three copies of both FAD2 and FAE1 as well as LFY, a known single copy gene in other species. All three copies of both CsFAD2 and CsFAE1 are expressed in developing seeds, and sequence alignments show that previously described conserved sites are present, suggesting that all three copies of both genes could be functional. The regions downstream of CsFAD2 and upstream of CsFAE1 demonstrate co-linearity with the Arabidopsis genome. In addition, three expressed haplotypes were observed for six predicted single-copy genes in 454 sequencing analysis and results from flow cytometry indicate that the DNA content of C. sativa is approximately three-fold that of diploid Camelina relatives. Phylogenetic analyses further support a history of duplication and indicate that C. sativa and C. microcarpa might share a parental genome.ConclusionsThere is compelling evidence for triplication of the C. sativa genome, including a larger chromosome number and three-fold larger measured genome size than other Camelina relatives, three isolated copies of FAD2, FAE1, and the KCS17-FAE1 intergenic region, and three expressed haplotypes observed for six predicted single-copy genes. Based on these results, we propose that C. sativa be considered an allohexaploid. The characterization of fatty acid synthesis pathway genes will allow for the future manipulation of oil composition of this emerging biofuel crop; however, targeted manipulations of oil composition and general development of C. sativa should consider and, when possible take advantage of, the implications of polyploidy.

More extensive genotyping across DRD2 and ANKK1 suggests that the association with alcohol dependence observed in this region may be due to genetic variants in the ANKK1 gene. ANKK1 is involved in signal transduction pathways and is a plausible biological candidate for involvement in addictive disorders.