Genes of The Thin

Underweight, defined as a body mass index (BMI, the ratio of weight in kilograms on height in meters squared) less than 18.5 is associated with a high risk of death (mortality is twice higher, compared to people with a BMI between 18.5 and 25). An international collaboration led by the team of Philippe Froguel, from Imperial College London, and that of Jacques Beckmann, University of Lausanne, has discovered a genetic defect responsible for the extreme thinness: People have three copies instead of two genes from a certain region of chromosome 16. About one in 2000 would present this excess of genes, resulting in a risk 20 times higher than average to have a body mass index below 18.5.

In 2010, geneticists have shown that this fragment of chromosome 16 is involved in one percent of severe cases of obesity, when there is only one of the two copies of the chromosome. In general, an individual has two copies of chromosome 16, one inherited from her mother and one of his father. In seeking the number of copies of this region of chromosome 16 in the genome of 100 000 people, scientists have identified 138 people this time with three copies.

Two thirds of them have inherited the mutation from their parents, one third have a spontaneous mutation. Half of children with this mutation are underweight and very difficult to feed. Some suffer from a developmental disorder and may, for four years, weigh the weight of a child aged one year and a half. According to Philippe Froguel, among the 28 genes in the supernumerary fragment, those involved in the pathology regulate appetite and satiety. It remains to identify which to understand how they have opposite effects depending on whether they are under-or over-represented.