生物谷报道：美国康奈尔大学等单位的研究人员，最近鉴别出决定狗体型大小的关键基因IGF1，向弄清人类体型大小差异迈出重要一步。相关文章被选为4月6日《Science》封面文章。
研究人员通过在骨骼尺寸变化较大的葡萄牙水犬（Portuguese water dogs）中对比个体DNA差异，发现小体型和大体型个体有差异的基因组区域。其中一个区域包括编码胰岛素样生长因子1（insulin-like growth factor 1，IGF1）基因，于是研究人员在开始包括奇瓦瓦犬（Chihuahuas）、玩具更犬（Toy Fox Terrier）和博美犬( Pomeranian)在内的14种小体型狗和包括猎狼犬（Irish wolfhounds）、圣伯纳犬(Saint Bernard)和大丹犬(Great Dane)在内的9种大体型狗中分析此区域。
图左为猎狼犬，右为奇瓦瓦犬
奇怪的是，大多数小体型狗拥有一段与大体型葡萄牙水犬相似的DNA片段，但大体积葡萄牙水犬、狼犬和豺狗等野生犬中没有这段DNA。研究人员推测，在狗驯化历史早期出现的一个基因突变，产生了“小狗”版的IGF1， 并随着驯化过程逐渐在小体型狗中固定下来，提示IGF1在决定同一品种狗体型大小差异中的作用，与在小体型狗品种与大体型狗品种分离过程中的作用相似。
“这么多种小体积狗品种是由对同一个基因的同一种突变的选择实现的，令人惊愕。这些结果提示尽管不同品系间存在各种各样的差异（甚至基因大小），IGF1作为一个一贯影响体型大小的基因，在众多小体积品种狗的进化过程种发挥重要作用，” Bustamante说，研究证明了家狗模式系统对鉴定重要基因（研究）中的作用。
因为小体型狗品种相互间亲缘关系较远，研究人员认为小体型狗间的基因变异在进化历史中出现较早，通过若干代的人工选育，现代狗已经成为个体间体型差异最大的哺乳动物。
Science 6 April 2007:
Vol. 316. no. 5821, pp. 112 - 115
DOI: 10.1126/science.1137045
Reports
A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs
Nathan B. Sutter,1 Carlos D. Bustamante,2 Kevin Chase,3 Melissa M. Gray,4 Keyan Zhao,5 Lan Zhu,2 Badri Padhukasahasram,2 Eric Karlins,1 Sean Davis,1 Paul G. Jones,6 Pascale Quignon,1 Gary S. Johnson,7 Heidi G. Parker,1 Neale Fretwell,6 Dana S. Mosher,1 Dennis F. Lawler,8 Ebenezer Satyaraj,8 Magnus Nordborg,5 K. Gordon Lark,3 Robert K. Wayne,4 Elaine A. Ostrander1*
The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.
1 National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892–8000, USA.
2 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14850, USA.
3 Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
4 Department of Ecology and Environmental Biology, University of California, Los Angeles, CA 90095, USA.
5 Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
6 The WALTHAM Centre for Pet Nutrition, Waltham on the Wolds, Leicestershire, LE14 4RT, UK.
7 Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
8 Nestle Research Center (NRC-STL), St. Louis, MO 63164, USA.
* To whom correspondence should be addressed. E-mail: eostrand@mail.nih.gov
