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

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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.

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    ABSTRACT: The mechanism(s) responsible for diversity of human height remain poorly understood at a molecular level. Clearly, genetics plays an important role as, in general, tall parents breed tall children, average-sized parents breed average-sized children, and small parents breed small children. With the critical role of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in the regulation of human statural growth, variations in the amounts of hormones produced and/or to the responsiveness of tissues to them could underlie such height diversity. To that end, various biochemical studies to date have reported that taller children produce greater amounts of GH and IGF-I than do shorter children (1,2). Other research has noted increased acute sensitivity to GH (measured by IGF-I generation) in taller than in normal-sized children (3). With regard to hormone sensitivity in humans, recently two isoforms of the GH receptor (GHR), a full-length version and another lacking exon 3 (d3-GHR) generated by retention or exclusion of exon 3 of the GHR gene during splicing, have been described. Approximately 50% of Europeans are either heterozygous or homozygous for the d3-GHR. In 2006, Dos Santos et al (4) reported that the d3-GHR was associated with increased stature after one year of GH therapy in children with idiopathic short stature. Subsequent studies aimed at verifying this initial observation and others attempting to link the d3-GHR to responsiveness to GH treatment in other disorders associated with short stature, including GH deficiency, small-for-gestational age, and Turner syndrome, have yielded conflicting results (5-8). Variations in in vitro IGF-I sensitivity have been reported in African Efe Pygmies and could account for their short stature (9).

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