Fellowships Grants and Awards November 2003 Toxicogenomics
Journal: Environmental Health Perspectives (2003)

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) solicits research proposals to identify and characterize genes that contribute to individual susceptibility to alcoholism and alcohol-related behaviors.This PA encourages multidisciplinary studies using advanced genetic and genomics technologies to find and characterize candidate genes in humans and animal models.Genetic linkage and association studies have identified many chromosomal regions and quantitative trait loci (QTL) associated with complex phenotypes related to alcohol induced behaviors and/or alcoholism.However, the large number of genes residing in those previously identified chromosomal regions/QTLs remain undefined, due to the lack of power and sensitivity of previously available methodology and technology.The completion of the sequences of the human and mouse genomes, and the development of new genomics technologies, have the potential for rapidly advancing the discovery of genes associated with alcoholism and alcohol-related behaviors.NIAAA seeks research applications that will explore and develop innovative computational, statistical, and molecular approaches to increase the power of gene discovery.Areas of emphasis include utilizing advanced technologies such as high-throughput SNP genotyping, haplotype pattern mining, admixture linkage disequilbrium mapping, and DNA pooling for fine mapping.Currently, haplotype maps for both human and mouse genomes are being developed and these maps will provide an additional resource for finding genes.Once fine mapping has further characterized a previously identified QTL or chromosomal region, candidate nucleotide variants within the locus can be identified.Some methods that could be used for fine mapping include high-throughput sequencing, RAGE, SAGE, DNA microarrays, protein arrays, and other high-throughput approaches.Many genes are predicted to reside within a QTL, and multiple polymorphisms are likely to be located in both coding and regulatory regions.Functional tests of candidate genes are needed to determine if the polymorphism(s) or genetic variants are relevant to the alcohol-induced trait.These tests may include the development of transgenic animals, such as BAC and YAC transgenics carrying chromosomal regions that contain large regulatory sequences.This PA specifically seeks applications that propose human or animal studies to identify and characterize genes associated with alcoholism and alcohol-related behaviors.Behaviors include alcohol consumption, tolerance/dependence, sensitivity/sedation, withdrawal, reinforcement, craving, and relapse.Genes identified may be used to develop markers for alcohol vulnerability and dependence.In addition, these genes may also be used to identify potential therapeutic targets and to predict individual responses to medications that treat alcoholism.Examples of research areas appropriate to this announcement include, but are not limited to: 1) identification and characterization of genes associated with alcoholism and alcoholrelated behaviors in the chromosomal regions previously identified in humans or animal models; 2) identification of genetic variants (SNPs/haplotpes) of associated with alcoholism and alcohol-related behaviors among the different populations, which will have high potential as targets for developing pharmacotherapeutic agents; 3) discovery of new genes associated with alcoholism and alcoholrelated behaviors and determination of functional relevance of the candidate genes and their polymorphic variants.This PA will use the NIH R01 and Exploratory/Developmental