September 1, 2011
Genetic Cause Of Extreme Thinness Identified
People with surplus copies of certain genes are much more prone to extreme thinness, as well as a syndrome in children known as "failure to thrive," according to a study published Thursday in the journal Nature.
One in 2,000 people have part of their chromosome 16 duplicated, with men 23 times and women five times more likely to be seriously underweight in these cases, the researchers found.
A person typically inherits a copy of each chromosome from each parent, giving us two copies of each gene. However, sometimes sections of a chromosome can be duplicated or deleted, resulting in an abnormal 'dosage' of genes.
"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,” said Philippe Froguel of the School of Public Health at Imperial College London, who led the study.
Froguel and colleagues examined the DNA of over 95,000 people searching for patterns linked to extreme thinness, and found that duplication of a part of chromosome 16 containing 28 genes is highly associated to being underweight.
The researchers defined underweight as a body-mass index (BMI) below 18.5, with normal weight corresponding to a BMI of 18.5 to 25, overweight corresponding to a BMI of 25-to-30, and obese meaning a BMI greater than 30.
Nearly half of all the children in the study with this particular genetic irregularity had been diagnosed with "failure to thrive," and did not gain weight normally as they grew older.
"One reason (the new finding) 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," said Froguel in a statement.
Additionally, one-in-four study participants with the surplus genes had microcephaly, a condition in which the head and brain are abnormally small. The disorder is also associated with neurological defects and a shorter life expectancy.
Last year, the researchers discovered that people missing a copy of these genes are 43 times more likely to be morbidly obese, something Froguel called “the first example of a deletion and a duplication of one part of the genome having opposite effects.”
While previous research has identified a large number of genetic changes that lead to obesity, this study is the first to pinpoint a genetic cause of thinness, Froguel said.
"At the moment we don't know anything about the genes in this region. 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,” he said.
Froguel said the next step is to sequence the genes to determine which ones are involved in regulating appetite.
Duplications in the part of chromosome 16 identified in the study have previously been linked with schizophrenia, and deletions with autism.
The study was published September 1 in the journal Nature.
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