Gene Found for Early-Onset Obesity

Scientists investigating the genetic differences between DNA samples from around 200 people with early-onset obesity and people with normal weight have found a striking difference between these groups: those with hyperphagia, an overeating disorder, had a high frequency of a gene named COB1 by Myriad Genetics, Inc. (Salt Lake City, UT, USA), which conducted the investigation.

The COB1 gene is the first common genetic mutation to be associated with childhood obesity. Although it was previously known to be involved in the regulation of insulin signaling, it was not known to be linked to hyperphagia. People with early-onset obesity have a markedly increased risk for type 2 diabetes. The COB1 gene has potential as a drug target to treat obese children and may also help diagnose the exact cause of the disease.

The Myriad scientists utilized a novel proprietary technology developed by Myriad to advance traditional positional cloning, the technique used in the 1990s to discover genes such as BRCA1 and BRCA2 genes for breast cancer and ovarian cancer. Certain aspects of COB1's biology are already known. For example, it has a prominent role in the regulation of insulin signaling. Insulin acts on certain neurons to inhibit food intake. Mutations in COB1 may alter this signaling and promote abnormal eating behavior.

The link between COB1 and hyperphagia was discovered with genomic DNA from a large number of people. This DNA was combined in equal amounts into a pool and hybridized to a high-density single nucleotide polymorphism (SNP) array. Each one of the 100,000 different SNPs, representing parts of genes in the human genome, was analyzed for its relative proportion of hybridized DNA and compared to the total amount in the pool. This provides a quantitative frequency of each gene in the disease samples when compared with known controls. When one gene frequency is over- or under-represented by a sufficient margin, a disease association can be proposed. In the case of COB1, the association was highly robust.



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