Abstract # 4550 Poster # 176:

Scheduled for Friday, June 21, 2013 07:00 PM-09:00 PM: Session 21 (SG Foyer ABC) Poster Presentation


EXOME SEQUENCE COMPARISONS FOR FUNCTIONAL VARIATION IN AN INDIAN AND A CHINESE MACAQUE (MACACA MULATTA)

C. A. Driscoll1, K. Blackistone1, J. Clemente1, S. G. Lindell1, S. J. Suomi2 and C. S. Barr1
1National Institute on Alcohol Abuse and Alcoholism, NIH, Section on Comparative Behavioral Genomics, Laboratory of Neurogenetics, 5625 Fishers Lane, Rm 3S-32:MSC 9412, Bethesda, MD 20892-9412, USA, 2Laboratory of Comparative Ethology, NICHHD, NIH
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     Behavioral differences in stress reactivity and/or reward sensitivity relating to alcohol exposure are common across individuals and populations. Informative genetic polymorphisms hold particular interest as diagnostic and predictive tools of individual variation in addiction related behaviors. Here two rhesus macaque subjects, one half Chinese and one Indian, typified by marked differences in reactivity and temperament, were characterized for genome-wide protein-coding variation. Exploiting the phylogenetically close relationship between human and macaque we leveraged the high degree of sequence similarity between them by using a human-based exon assay on the Illumina platform, successfully resolving 65% of the sequences expected from a human-on-human assay. After light filtering (depth of coverage > 6), approximately 140,000 SNPs were called in target regions. Non-synonymous SNPs (variants that predicted amino acid changes), were found in the coding regions of six behavior related genes (MPDZ, TDRD1, GAL, CRTAC1, GABRA6, CRHR2), some of which are predicted to be potentially deleterious by in silico analysis. All variants from the six candidate genes were verified by Sanger sequencing in 25 samples including the two individuals that were exome sequenced. Variation in the GABA-A receptor (encoding the alpha-6 subunit) and CRHR2 (corticotropin releasing hormone receptor) has been shown to predict individual differences in alcohol and stress response. These promising techniques are now being extended to New World and Old World monkeys, and the lesser and greater apes.