Abstract # 67:

Scheduled for Thursday, August 18, 2005 07:00 PM-09:00 PM: (Cambridge/Oxford Room) Poster Presentation


SEQUENCE VARIATION IN THE 5’-FLANKING REGION OF THE Macaca mulatta NEUROPEPTIDE Y GENE

C. S. Barr1,2, S. G. Lindell1, T. K. Newman1,2, S. Higley3, S. J. Suomi3, D. Goldman2 and J. D. Higley1
1NIH/NIAAA-Laboratory of Clinical and Translational Studies, NIH Animal Center, Poolesville, MD 20837, USA, 2NIH/NIAAA- Laboratory of Neurogenetics, 3NIH/NICHD-Laboratory of Comparative Ethology
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     Neuropeptide Y (NPY) is an anxiolytic peptide that is involved in modulation of stress response. As such, the NPY gene may be a good candidate for investigating genetic variation as it relates to individual differences in anxious responding and vulnerability to stress in nonhuman primates. In humans, a functional variant in the NPY gene (Leu7Pro) results in decreased release of mature NPY from neuron terminals and is associated with stress-related disorders. We wanted to sequence the rhesus NPY gene to screen for genetic variation. Sequences of the Macaca mulatta NPY gene and 5’-flanking region were determined using PCR and direct sequencing from genomic DNA. DNA samples from 96 animals at the National Institutes of Health Animal Center were sequenced, and variants were detected by direct visualization of electropherograms generated by Applied Biosystems Sequencing Analysis software. Primers were designed from published human sequence and, subsequently, from rhesus sequence generated in our lab. Six polymorphisms were identified in the 5’-flanking region of the NPY gene. One of these is adjacent to a GRE 1/2 site, which could potentially disrupt glucocorticoid receptor-mediated regulation of NPY transcription. Consistent with the demonstrated role for corticosteroids in induction of NPY, haplotype analysis revealed that carriers of this genetic variant exhibited lower cerebrospinal fluid levels of NPY (n = 50, P ≤ 0.05). This NPY promoter variant may also influence behavioral and neuroendocrine responses to stress in rhesus macaques.