A PYY Q62P variant linked to human obesity
| Autor: | Len A. Pennacchio, Nadav Ahituv, Robert Dent, Wendy Schackwitz, Heather Doelle, Ruth McPherson, John Michael Collier, Anna Ustaszewska, Sybil Hébert, Nihan Kavaslar |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Candidate gene Sequence analysis Molecular Sequence Data Mutation Missense Biology medicine.disease_cause Exon Eating Mice Internal medicine Genetics medicine Pancreatic polypeptide Animals Humans Genetic Predisposition to Disease Peptide YY Amino Acid Sequence Obesity Molecular Biology Gene Genetics (clinical) Mutation Life Sciences General Medicine Fasting Sequence Analysis DNA medicine.disease Postprandial Period Pedigree Endocrinology Case-Control Studies Sequence Alignment |
| Zdroj: | Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy; Ustaszewska, Anna; Collier, John Michael; Hebert, Sybil; et al.(2005). A PYY Q62P variant linked to human obesity. Lawrence Berkeley National Laboratory. Lawrence Berkeley National Laboratory: Lawrence Berkeley National Laboratory. Retrieved from: http://www.escholarship.org/uc/item/2060q8g7 |
| ISSN: | 0964-6906 |
| Popis: | Members of the pancreatic polypeptide family and their receptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysis of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|