犬类全基因组关联研究发现DENND 1 B是狗和人类的肥胖基因
犬类全基因组关联研究发现DENND1B是狗和人类的肥胖基因
作者： 小柯机器人 发布时间：2025/3/7 14:15:14
本期文章：《科学》：Online/在线发表
英国剑桥大学Eleanor Raffan小组宣布他们揭示了犬类全基因组关联研究发现DENND1B是狗和人类的肥胖基因。相关论文发表在2025年3月6日出版的《科学》杂志上。
课题组研究人员对241只拉布拉多猎犬进行了身体状况评分（一种衡量肥胖的指标）的犬全基因组关联研究。通过跨物种方法，课题组研究人员发现犬类肥胖基因也与人类罕见和常见的肥胖形式有关。犬的主要关联基因位于DENN结构域（DENND1B）内。交替等位基因的每个拷贝与约7%的体脂增加相关。该研究组证明了该基因在调节黑素皮质素4受体的信号传导和运输中的作用，黑素皮质素4受体是能量稳态的关键控制器。然后，犬类遗传学确定了与狗和人类相关的肥胖基因和机制。
据了解，肥胖是一种遗传性疾病，但其遗传基础尚不完全清楚。犬类种群历史有助于性状定位。
附：英文原文
Title: Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans
Author: Natalie J. Wallis, Alyce McClellan, Alexander Mrseburg, Katherine A. Kentistou, Aqfan Jamaluddin, Georgina K. C. Dowsett, Ellen Schofield, Anna Morros-Nuevo, Sadia Saeed, Brian Y. H. Lam, Natasha T. Sumanasekera, Justine Chan, Sambhavi S. Kumar, Rey M. Zhang, Jodie F. Wainwright, Marie Dittmann, Gabriella Lakatos, Kara Rainbow, David Withers, Rebecca Bounds, Marcella Ma, Alexander J. German, Jane Ladlow, David Sargan, Philippe Froguel, I. Sadaf Farooqi, Ken K. Ong, Giles S. H. Yeo, John A. Tadross, John R. B. Perry, Caroline M. Gorvin, Eleanor Raffan
Issue&Volume: 2025-03-06
Abstract: Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score, a measure of obesity, in 241 Labrador retrievers. Using a cross-species approach, we showed canine obesity genes are also associated with rare and common forms of obesity in humans. The lead canine association was within the gene DENN domain containing 1B (DENND1B). Each copy of the alternate allele was associated with ~7% greater body fat. We demonstrate a role for this gene in regulating signaling and trafficking of melanocortin 4 receptor, a critical controller of energy homeostasis. Thus, canine genetics identified obesity genes and mechanisms relevant to both dogs and humans.
DOI: ads2145
Source: https://www.science.org/doi/10.1126/science.ads2145