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Peptide YY (PYY) has been implicated in the control of food intake through functional
studies in rodents and humans. To investigate whether genetic alterations within this
gene result in abnormal weight in humans, we sequenced its coding exons and splice sites
in a large cohort of extremely obese [n=379; average body mass index (BMI) 49.0 kg/m2]
and lean (n=378; average BMI 19.5 kg/m2) individuals. In total, three rare non-
synonymous variants were identified, only one of which, PYY Q62P, exhibited familial
segregation with body mass. Through serendipity, previous cell culture based studies
revealed this precise variant to have altered receptor binding selectivity in vitro. We
further show using mouse peptide injection experiments that while the wild-type PYY
peptide reduces food intake, the mutant PYY 62P had an insignificant effect in reducing
food intake in vivo. Taken together, these results are the first to support that rare
sequence variants within PYY can influence human susceptibility to obesity.
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Ruhl, J.E.; Ade, P.A.R.; Carlstrom, J.E.; Cho, H.M.; Crawford,T.; Dobbs, M. et al. The South Pole Telescope, article, November 4, 2004; (digital.library.unt.edu/ark:/67531/metadc885152/m1/2/: accessed October 20, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.