The overall goal of the Genomics and Molecular Biology Core of this Indiana Alcohol Research Center (IARC) is to support both human and animal studies that pursue the genes underlying alcohol-seeking behavior, alcoholism, and related diseases. The services offered will be contributing to the goals of the IARC by supporting research projects involved in identifying the genetic determinants of alcohol ingestion and response to ethanol, goals of the IARC. The Core has developed genotyping assays for the human alcohol metabolizing enzymes, ADH1B, ADH1C, ALDH2, and ALDH1A1 and has determined the allele frequencies of these loci in many collaborative studies. The Core has expanded its human genotyping services to include high throughput genotyping using the Sequenom MassArray system. For the ADH cluster of genes, 63 SNPs covering all 7 genes across the ADH region will be genotyped, resulting in haplotypes that are used in association studies. Likewise, SNP panels have been developed to genotype SNPs covering the GABA receptors and the cholinergic receptor, muscarinic 2 (CHRM2). To identify genes that are differentially expressed between high alcohol drinking and low alcohol drinking animal models under various experimental conditions, the Core will continue to offer microarray technology. These findings will help us understand the biological mechanisms of alcohol drinking by pointing to CMS pathways that are differentially changed between high and low drinking models as a result of alcohol drinking. This technology will also be used to determine whether alcohol exposure during critical periods of development result in differential gene expression between embryos from C57BI/6 and DBA/2 mice which are differentially vulnerable to alcohol exposure. The Core will offer quantitative Real-Time PCR as a means to verify differential expression of key genes identified by microarray technology. A new service of the Core will be to provide genetic monitoring of the alcohol preferring and nonpreferring rat lines and strains. An overall increase in accuracy and cost savings result in having the genotyping and microarray analyses performed in a core laboratory rather than having independent facilities. The Core services benefit the Human Component, and Dr. Davidson's pilot projects and numerous existing and future collaborators by performing genotyping of various genes, the Animal Production Core for genetic monitoring of their rat lines and strains, and the Rat Research and Fetal Alcohol Syndrome Components for microarray analyses and confirmation studies to identify candidate genes for alcohol-related phenotypes. In addition, the Core interacts with and is dependent on the guidance of the Administration Core. The findings of the Core, identification of genes that determine vulnerability to alcoholism, will advance the understanding of alcohol-seeking behavior and provide information for developing treatments to prevent excessive alcohol consumption.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA007611-24
Application #
8208639
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
24
Fiscal Year
2011
Total Cost
$151,945
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Ding, Zheng-Ming; Ingraham, Cynthia M; Hauser, Sheketha R et al. (2017) Reduced Levels of mGlu2 Receptors within the Prelimbic Cortex Are Not Associated with Elevated Glutamate Transmission or High Alcohol Drinking. Alcohol Clin Exp Res 41:1896-1906
Hendershot, Christian S; Wardell, Jeffrey D; McPhee, Matthew D et al. (2017) A prospective study of genetic factors, human laboratory phenotypes, and heavy drinking in late adolescence. Addict Biol 22:1343-1354
Czachowski, Cristine L; Froehlich, Janice C; DeLory, Michael (2017) The Effects of Long-Term Varenicline Administration on Ethanol and Sucrose Seeking and Self-Administration in Male P Rats. Alcohol Clin Exp Res :
Linsenbardt, David N; Smoker, Michael P; Janetsian-Fritz, Sarine S et al. (2017) Impulsivity in rodents with a genetic predisposition for excessive alcohol consumption is associated with a lack of a prospective strategy. Cogn Affect Behav Neurosci 17:235-251
Froehlich, Janice C; Fischer, Stephen M; Nicholson, Emily R et al. (2017) A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking. Alcohol Clin Exp Res 41:644-652
Weera, Marcus M; Fields, Molly A; Tapp, Danielle N et al. (2017) Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference. Alcohol Clin Exp Res :
Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E et al. (2017) Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats. Alcohol Clin Exp Res 41:1510-1517
Liang, Tiebing; Chalasani, Naga P; Williams, Kent Edward et al. (2017) Differential Expression of miRNAs in Nontumor Liver Tissue of Patients With Hepatocellular Cancer Caused by Nonalcoholic Steatohepatitis Cirrhosis. Clin Gastroenterol Hepatol 15:465-467
Gowin, Joshua L; Sloan, Matthew E; Stangl, Bethany L et al. (2017) Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption. Am J Psychiatry 174:1094-1101
King, Andrea C; Hasin, Deborah; O'Connor, Sean J et al. (2016) A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder. Biol Psychiatry 79:489-98

Showing the most recent 10 out of 280 publications