Gene ‘overdose’ significantly increases risk of extreme thinness
1 September 2011
In a study part-funded by the Wellcome Trust and the Medical Research Council, researchers from Imperial College London and the University of Lausanne examined the DNA of over 95 000 people and found that this duplication was associated with being underweight, defined as a body mass index below 18.5.
Half of all children with the duplication in the study have been diagnosed with a 'failure to thrive', meaning that their rate of weight gain is significantly lower than normal. A quarter of people with the duplication have microcephaly, a condition in which the head and brain are abnormally small, which is associated with neurological defects and shorter life expectancy.
Last year, the same researchers discovered that people with a missing copy of the particular genes in this segment of the chromosome are 43 times more likely to be morbidly obese. Duplications in this region have also been linked previously with schizophrenia and deletions with autism.
Professor Philippe Froguel from the School of Public Health at Imperial College London, who led the study, said: "The dogma is that we have two copies of each gene, but this isn't really true. The genome is full of holes where genes are lost, and in other places we have extra copies of genes. In many cases, duplications and deletions have no effect, but occasionally they can lead to disease.
"So far, we have discovered a large number of genetic changes that lead to obesity. It seems that we have plenty of systems that increase appetite since eating is so important - you can suppress one and nothing happens. This is the first genetic cause of extreme thinness that has been identified.
"One reason this is important is that it shows that failure to thrive in childhood can be genetically driven. If a child is not eating, it's not necessarily the parents' fault."
The finding is also the first example of a deletion and a duplication of one part of the genome having opposite effects. At the moment, it is not understood how the genes in this region affect our appetite and body weight. However, Professor Froguel believes that understanding why this gene duplication causes thinness may help in the development of new treatments for obesity and appetite disorders.
Image credit: Anne-Katrin Purkiss, Wellcome Images.
Reference
Jacquemont S et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 2011 (epub ahead of print).
