FTO gene

FTO is a gene on human chromosome 16 in which certain variants appear to be correlated with obesity in humans.

Association with obesity
A study by Frayling et al. published in the April 12, 2007 issue of Science Magazine has examined 38,759 Europeans for variants of FTO and identified an obesity risk allele. In particular, carriers of one copy of the allele weighed 1.2 kg more than people with no copies, on average. Carriers of two copies (16% of the subjects) weighed 3 kg more and had a 1.67-fold higher rate of obesity than those with no copies. The association was observed in ages 7 and upwards. The gene is also associated with increased risk of Type 2 Diabetes.

The authors claim that while obesity is known to have a genetic component (from twin studies), until their study, no other study that was replicated has ever identified a risk allele that was so common in the human population. The risk allele is a cluster of 10 single nucleotide polymorphism in the first intron of FTO called rs9939609. According to HapMap, it has population frequencies of 45% in the West/Central Europeans, 52% in Yorubans (West African natives) and 14% in Chinese/Japanese.

Function
The gene's abbreviation is FTO because a deletion in a homologous region in mice results in fused toes (FT) and other abnormalities. The gene name "Fatso" was given in 1999, before its association with obesity was known. The function of FTO is unknown. The study that found the gene, and the only study that experimentally looked at its function, is probably unsuitable for inferring the functional role because the deleted region involved five other genes.

Mechanism
The mechanism of action is also mysterious: "FTO is closely adjacent to a gene of unknown function KIAA1005 which is transcribed in the opposite direction. This opens up the possibility that genetic variation affects a regulatory element for KIAA1005: however, there is no obvious such variant within the 47 kb associated region". They conclude that an intron within the FTO gene is "most likely to contain the predisposing variant(s), but there is, at present, no clear genetic mechanism to explain how this alters the function or expression of FTO, KIAA1005 or more distant genes."

Technical Details
Chromosome: 16; Location: 16q12.2, also known as MGC5149; KIAA1752.

Type 2 Bardet-Biedl syndrome may involve chromosome 16. This syndrome is characterized by obesity.

The gene is especially active in the hypothalamus.