Small Dog Gene? The Canine IGF1 gene has a "small dog code"

[dogs4life]

Small breeds (adult under 20 lbs) have a mutation or regulatory sequence on the IGF1 gene where most giant breeds do not. It makes sense that the mutation is on the IGF1 gene since we know it's an important gene involved in growth regulation. So does this mean we can create and miniature Dane or a giant Chihuahua with gene manipulation? Gads, I hope not.

A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs -- Sutter et al. 316 (5821): 112 -- Science

From Science April 2007

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

Nathan B. Sutter, Carlos D. Bustamante, Kevin Chase, et al.

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.

Physorg.com - Ancient Genetic Material Keeps Pups Pint-Sized

Scientists track down the gene that turns Great Dane into a chihuahua - xenoMED

Insulin-like growth factor 1 - Wikipedia, the free encyclopedia

Insulin-like growth factor 1 (IGF-1) is a polypeptide protein hormone similar in molecular structure to insulin. It plays an important role in childhood growth and continues to have anabolic effects in adults.

Production and circulation

IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges. IGF-1 has a molecular weight of 7649 daltons. IGF-1 is produced primarily by the liver as an endocrine hormone as well as target tissues in a paracrine/autocrine fashion. Production is stimulated by growth hormone and can be retarded by undernutrition, growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signalling pathway post GH receptor including SHP2 and STAT5b. Approximately 98% of IGF-1 is always bound to one of 6 binding proteins (IGF-BP). IGFBP-3, the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio.

Action

Its primary action is mediated by binding to specific IGF receptors present on many cell types in many tissues. The signal is transduced by intracellular events. IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and multiplication and a potent inhibitor of programmed cell death.

Almost every cell in the human body is affected by IGF-1, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs. In addition to the insulin-like effects, IGF-1 can also regulate cell growth and development, especially in nerve cells, as well as cellular DNA synthesis.

Diseases of deficiency and resistance

Rare diseases characterized by inability to make or respond to IGF-1 produce a distinctive type of growth failure. One such disorder, termed Laron dwarfism does not respond at all to growth hormone treatment due to a lack of GH receptors. The FDA has grouped these diseases into a disorder called severe primary IGF deficiency. Patients with severe primary IGFD typically present with normal to high GH levels, height below -3 standard deviations (SD), and IGF-1 levels below -3SD. Severe primary IGFD includes patients with mutations in the GH receptor, post-receptor mutations or IGF mutations, as previously described. As a result, these patients cannot be expected to respond to GH treatment.

The IGF signaling pathway appears to play a crucial role in cancer. Several studies have shown that increased levels of IGF lead to an increased risk of cancer. Studies done on lung cancer cells show that drugs inhibiting such signaling can be of potential interest in cancer therapy.

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