FTO gains function

Abstract

Previous genome-wide association studies have identified a strong association between FTO and human obesity, although the mechanism by which FTO affects obesity remains unknown. Anew study suggests that the obesity risk alleles are gain-of-function.

Figure 1

Genomic organization of the FTO locus on chromosome 16 (16q12.2, at 52.3–52.4 Mbp). rs9939609, in linkage disequilibrium (LD) with rs8050136, is associated with body mass index (BMI) and is located in a 47-kb LD block. FTO is an AlkB-like demethylase with a strong preference for 3-methylthymidine (3-metT) in single-stranded nucleic acids. RPGRIP1L is a component of the basal body of the cilium. The leptin (LEPR) and melanin-concentrating hormone 1 (MCHR1) receptors localize to neuronal cilia. CUX1, which binds at rs8050136, regulates FTO and RPGRIP1L expression from a site located in the region of association in intron 1 of FTO. Not drawn to scale. Black boxes indicate exons