Morbidly obese are missing genes

A small number of extremely overweight people may be missing a section of their DNA, according to a new study.

Researchers from Imperial College London and ten other European Centres say that missing DNA such as that identified in this study may be having a dramatic effect on some people's weight.

According to the new research, around seven in every thousand morbidly obese people are missing a part of their DNA, containing approximately 30 genes. The authors of the study did not find this kind of genetic variation in any normal weight people.

Previous studies have identified several genetic variations that contribute to obesity, most of which are single mutations in a person's DNA that change the function of a gene.

The new research is the first to clearly demonstrate that obesity in otherwise physically healthy individuals can be caused by a rare genetic variation in which a section of a person's DNA is missing.

The researchers do not yet know the function of the missing genes, but previous research has suggested that some of them may be associated with delayed development, autism and schizophrenia.

People inherit two copies of their DNA, one from their mother and one from their father. Sometimes, missing one copy of one or several genes - as in the individuals identified in this latest study - can have a drastic effect on the body.

The research team, led by professor Philippe Froguel from the School of Public Health at Imperial College London, believes there may be other genetic deletions, in addition to those identified in the new study that increase a person's risk of becoming obese.

They hope that by identifying genetic variations causing people to be extremely obese, they can develop genetic tests to help determine the best course of treatment for these individuals.

Froguel and colleagues first identified the missing genes in teenagers and adults who had learning difficulties or delayed development. They found 31 people who had nearly identical 'deletions' in one copy of their DNA. All of the adults with this genetic change had a BMI of over 30, which means they were obese.

The researchers then went on to study the genomes of 16,053 people who were either obese or normal weight, (with a BMI between 18.5 and 25), from eight European cohorts. They identified 19 more people with the same genetic deletion, all of whom were severely obese, but did not find the deletion in any healthy normal weight people.

This means the genetic deletion was found in seven in every 1,000 morbidly obese people, making it the second most frequent known genetic cause of obesity.

People with the deletion tended to be normal weight toddlers, becoming overweight during childhood and then severely obese as adults. The researchers also looked at the genomes of their parents, and found that 11 people inherited the deletion from their mother and four from their father, with ten of the deletions occurring by chance. All the parents with the deletion were also obese.

The new research has been published in the journal Nature.