A single IGF1 allele is a major determinant of small size in dogs

被引:491
作者
Sutter, Nathan B.
Bustamante, Carlos D.
Chase, Kevin
Gray, Melissa M.
Zhao, Keyan
Zhu, Lan
Padhukasahasram, Badri
Karlins, Eric
Davis, Sean
Jones, Paul G.
Quignon, Pascale
Johnson, Gary S.
Parker, Heidi G.
Fretwell, Neale
Mosher, Dana S.
Lawler, Dennis F.
Satyaraj, Ebenezer
Nordborg, Magnus
Lark, K. Gordon
Wayne, Robert K.
Ostrander, Elaine A.
机构
[1] NHGRI, Bethesda, MD 20892 USA
[2] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14850 USA
[3] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
[4] Univ Calif Los Angeles, Dept Ecol & Environm Biol, Los Angeles, CA 90095 USA
[5] Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA
[6] WALTHAM Ctr Pet Nutr, Melton Mowbray LE14 4RT, Leics, England
[7] Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA
[8] Nestle Res Ctr NRC STL, St Louis, MO 63164 USA
关键词
D O I
10.1126/science.1137045
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:112 / 115
页数:4
相关论文
共 28 条
[1]  
BAKER J, 1993, CELL, V75, P73, DOI 10.1016/0092-8674(93)90680-O
[2]   Interaction between the X chromosome and an autosome regulates size sexual dimorphism in Portuguese Water Dogs [J].
Chase, K ;
Carrier, DR ;
Adler, FR ;
Ostrander, EA ;
Lark, KG .
GENOME RESEARCH, 2005, 15 (12) :1820-1824
[3]   Genetic basis for systems of skeletal quantitative traits: Principal component analysis of the canid skeleton [J].
Chase, K ;
Carrier, DR ;
Adler, FR ;
Jarvik, T ;
Ostrander, EA ;
Lorentzen, TD ;
Lark, KG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (15) :9930-9935
[4]   Overview of the IGF-I system [J].
Cohen, P .
HORMONE RESEARCH, 2006, 65 :3-8
[5]   BODY SIZE PARALLELS INSULIN-LIKE GROWTH FACTOR-I LEVELS BUT NOT GROWTH-HORMONE SECRETORY CAPACITY [J].
EIGENMANN, JE ;
PATTERSON, DF ;
FROESCH, ER .
ACTA ENDOCRINOLOGICA, 1984, 106 (04) :448-453
[6]  
Epstein H., 1971, ORIGIN DOMESTIC ANIM, VII.
[7]   Large body size in the dog is associated with transient GH excess at a young age [J].
Favier, RP ;
Mol, JA ;
Kooistra, HS ;
Rijnberk, A .
JOURNAL OF ENDOCRINOLOGY, 2001, 170 (02) :479-484
[8]   Molecular origins of rapid and continuous morphological evolution [J].
Fondon, JW ;
Garner, HR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (52) :18058-18063
[9]   Regulation of apoptosis by insulin-like growth factor (IGF)-I [J].
Kooijman, Ron .
CYTOKINE & GROWTH FACTOR REVIEWS, 2006, 17 (04) :305-323
[10]   Genome sequence, comparative analysis and haplotype structure of the domestic dog [J].
Lindblad-Toh, K ;
Wade, CM ;
Mikkelsen, TS ;
Karlsson, EK ;
Jaffe, DB ;
Kamal, M ;
Clamp, M ;
Chang, JL ;
Kulbokas, EJ ;
Zody, MC ;
Mauceli, E ;
Xie, XH ;
Breen, M ;
Wayne, RK ;
Ostrander, EA ;
Ponting, CP ;
Galibert, F ;
Smith, DR ;
deJong, PJ ;
Kirkness, E ;
Alvarez, P ;
Biagi, T ;
Brockman, W ;
Butler, J ;
Chin, CW ;
Cook, A ;
Cuff, J ;
Daly, MJ ;
DeCaprio, D ;
Gnerre, S ;
Grabherr, M ;
Kellis, M ;
Kleber, M ;
Bardeleben, C ;
Goodstadt, L ;
Heger, A ;
Hitte, C ;
Kim, L ;
Koepfli, KP ;
Parker, HG ;
Pollinger, JP ;
Searle, SMJ ;
Sutter, NB ;
Thomas, R ;
Webber, C ;
Lander, ES .
NATURE, 2005, 438 (7069) :803-819