Article

A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs

National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892-8000, USA.
Science (Impact Factor: 31.48). 05/2007; 316(5821):112-5. DOI: 10.1126/science.1137045
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Badri Padhukasahasram, Jul 07, 2015
0 Followers
 · 
230 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genomic resources developed for domesticated species provide powerful tools for studying the evolutionary history of their wild relatives. Here we use 61K single-nucleotide polymorphisms (SNPs) evenly spaced throughout the canine nuclear genome to analyse evolutionary relationships among the three largest European populations of grey wolves in comparison with other populations worldwide, and investigate genome-wide effects of demographic bottlenecks and signatures of selection. European wolves have a discontinuous range, with large and connected populations in Eastern Europe and relatively smaller, isolated populations in Italy and the Iberian Peninsula. Our results suggest a continuous decline in wolf numbers in Europe since the Late Pleistocene, and long-term isolation and bottlenecks in the Italian and Iberian populations following their divergence from the Eastern European population. The Italian and Iberian populations have low genetic variability and high linkage disequilibrium, but relatively few autozygous segments across the genome. This last characteristic clearly distinguishes them from populations that underwent recent drastic demographic declines or founder events, and implies long-term bottlenecks in these two populations. Although genetic drift due to spatial isolation and bottlenecks seems to be a major evolutionary force diversifying the European populations, we detected 35 loci that are putatively under diversifying selection. Two of these loci flank the canine platelet-derived growth factor gene, which affects bone growth and may influence differences in body size between wolf populations. This study demonstrates the power of population genomics for identifying genetic signals of demographic bottlenecks and detecting signatures of directional selection in bottlenecked populations, despite their low background variability.Heredity advance online publication, 18 December 2013; doi:10.1038/hdy.2013.122.
    Heredity 12/2013; DOI:10.1038/hdy.2013.122 · 3.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this paper we develop a novel mathematical model of the insulin-TOR-MAPK signaling network that controls growth. Most data on the properties of the insulin and MAPK signaling networks are static and the responses to experimental interventions, such as knockouts, overexpression, and hormonal input are typically reported as scaled quantities. The modeling paradigm we develop here uses scaled variables and is ideally suited to simulate systems in which much of the available data are scaled. Our mathematical representation of signaling networks provides a way to reconcile theory and experiments, thus leading to a better understanding of the properties and function of these signaling networks. We test the performance of the model against a broad diversity of experimental data. The model correctly reproduces experimental insulin dose-response relationships. We study the interaction between insulin and MAPK signaling in the control of protein synthesis, and the interactions between amino acids, insulin and TOR signaling. We study the effects of variation in FOXO expression on protein synthesis and glucose transport capacity, and show that a FOXO knockout can partially rescue protein synthesis capacity of an insulin receptor (INR) knockout. We conclude that the modeling paradigm we develop provides a simple tool to investigate the qualitative properties of signaling networks.
    Frontiers in Physiology 09/2013; 4:245. DOI:10.3389/fphys.2013.00245 · 3.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have confirmed that insulin growth factor-1 (IGF1) plays important roles in growth and body size in humans and animals. However, whether single nucleotide polymorphisms (SNPs) within the IGF1 gene affects body size and growth in pigs has been unclear. We identified IGF1 SNPs among 5 pig breeds (Berkshire, Duroc, Landrace, Yorkshire and Korea Native Pig) and found that the G allele of SNP (c.G189A) was associated with higher body weight and was more predominant in western pig breeds, while the Korean Native Pig is the breed with the highest frequency of the A allele. Four haplotypes (–GA–, –GG–, –AG–, and –AA–) were constructed using the 2 identified SNPs. The GA haplotype was most frequently observed, except in the Berkshire breed. In addition, these SNPs and haplotypes were significantly associated with body size (final weight), average daily gain, and backfat thickness (P < 0.05) in 2 intercrossed F2 pig populations (KNP × YS F2 and KNP × LR F2). Furthermore, the major GA haplotype had a significant additive effect on body size and average daily gain. In conclusion, specific SNPs within the porcine IGF1 gene may contribute to the smaller body size and lower growth rate of Korea Native Pigs.
    Genes & genomics 08/2013; 35(4). DOI:10.1007/s13258-013-0098-0 · 0.57 Impact Factor