Extreme thinness may not be only about dieting or exercise. Scientists have identified a genetic factor, according to a study published on Wednesday in the journal Nature. The research shows that people with extra copies of certain genes are much more likely to be very skinny.
Under normal conditions humans have a copy of each chromosome from each parent, making it two copies of each gene. But sometimes sections of a chromosome can be duplicated or deleted, resulting in an abnormal dose of genes.
According to the study, part of chromosome 16 is duplicated in one among 2,000 people, making such men 23 times and such women five times more likely to be underweight.
Researchers at Imperial College London and the University of Lausanne in Switzerland examined the DNA of more than 95,000 people to verify that duplication of a part of chromosome 16 is associated with being underweight, defined as body mass index below 18.5. Half of all children with the duplication in the study have been diagnosed with a failure to thrive as 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 these genes are 43 times more likely to be morbidly obese.
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, said Professor Philippe Froguel, from the School of Public Health at Imperial College London, who led the study. 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, he said.
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, Froguel said. If we can work out why gene duplication in this region causes thinness, it might throw up new potential treatments for obesity and appetite disorders. We now plan to sequence these genes and find out what they do, so we can get an idea of which ones are involved in regulating appetite.