The Rutgers University Cell and DNA Repository (RUCDR, IRPG site 8, Shared Resource XI) will support the broad objectives of the eight site, investigator initiated IRPG """"""""Novel Phenotypes for Genetic Analysis of Alcoholism"""""""". The seven participating IRPG sites will submit blood obtained from phenotypically well characterized individuals in families that exhibit multiple, well-documented histories of alcoholism as well as individuals from control families. RUCDR will utilize the blood to produce transformed lymphocyte cell lines (LCLS) from which DNA is extracted. RUCDR then submits the DNAs to the genotyping laboratories (Shared Resource VIII) for molecular analysis of marker allele polymorphisms. Statistical analyses of the genotype data will ultimately permit the identification of quantitative trait loci (QTLS) that play major roles in alcoholism susceptibility and severity. The current IRPG approach is to ascertain linkage of novel quantitative phenotypes to polymorphic micro satellite repeat loci, initially at 10 centimorgan intervals but at greater resolution as the data warrant. Linkage to candidate genes will also be tested. Novel alcoholism phenotypes include quantitative indices of neurophysiological disinhibition, dependence, withdrawal, craving, and tolerance. However, a definition of the chromosomal location and, subsequently, the identity of genes involved in the expression of these novel phenotypes will require unknown amounts of high quality DNA from individual subjects. Relatively large amounts of DNA can only be assured with a renewable resource (e.g. viable LCL cultures). A LCL and DNA repository facilitates gene identification through linkage studies and may also foster future metabolic and biochemical analyses of alcoholism related phenotypes that are expressed in LCLs. Thus, the LCL and DNA banks provide an extremely valuable, long-term, renewable resource for investigations of both the genetic and physiologic bases of alcoholism.
