Abstract # 166:

Scheduled for Sunday, August 27, 2017 09:30 AM-09:45 AM: (Grand Ballroom) Oral Presentation


AN INTEGRATIVE APPROACH FOR EVALUATING RHESUS MACAQUE SOCIAL BEHAVIOR: WHOLE GENOME SEQUENCING REVEALS A NATURAL LOSS-OF-FUNCTION MUTATION IN THE NEURONAL SCAFFOLDING PROTEIN GRIP1$

M. J. Montague1, N. Snyder-Mackler2, S. Madlon-Kay1, L. J. Brent3, J. H. Skene2, J. E. Horvath4 and M. L. Platt1
1University of Pennsylvania, Department of Neuroscience, Perelman School of Medicine, Philadelphia, PA 19104, USA, 2Duke University, 3University of Exeter, 4North Carolina Central University
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     Evidence suggests that individual variation in social behavior arises from a combination of genetic predispositions and individual experience, yet the underlying biological mechanisms remain poorly understood. To address this gap, we have sought to understand the genetic contributions to social behavior in a large, free-ranging population of rhesus macaques (Macaca mulatta) with a known pedigree and detailed behavioral phenotypes. We hypothesized that genetic variants underlying molecular differences in neuroreceptors may be associated with behavioral variation in this socially complex species. For example, glutamate receptor interacting protein 1 (GRIP1) helps to stabilize glutamate receptors at excitatory synapses, and studies of neuronal-specific loss-of-function mice resulted in increased rates of prosocial behavior. To this end, we generated whole genome sequences for 217 individuals and identified over nineteen million population-wide single nucleotide variants, including those that alter amino acid changes in neuromodulatory pathway genes, including dopamine receptors, oxytocin and vasopressin receptors, serotonin transporters, and the mu-1 opioid receptor. Of the 2,022 highest-impact variants, seventeen were predicted to affect candidate genes for autism spectrum disorders, per the online database, SFARI Gene. One such variant, with a population allele frequency of 0.16, was predicted to eliminate the start codon of GRIP1. We describe the social behavior among the seventeen heterozygous and eleven homozygous macaques with this variant, suggesting approaches for integrating natural loss-of-function mutations with long-term behavioral data.