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Monday, 07 December 2009 19:28

Missing chunks of DNA may lead to obese children

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According to a British report highlighted in the journal Nature, the lack of large, rare chromosomes could be the hereditary cause of severe early-onset obesity.


The Nature paper “Large, rare chromosomal deletions associated with severe early-onset obesity” (doi:10.1038/nature08689) was published online on Sunday, December 6, 2009.

It is authored by Elena G. Bochukova, Julia Keogh, Elena Henning, Carolin Purmann, Kasia Blaszczyk, Sadia Saeed, Stephen O'Rahilly, and I. Sadaf Farooqi (all from the University of Cambridge, U.K.); Ni Huang and Matthew E. Hurles (both from the Wellcome Trust Sanger Institute, U.K.); Julian Hamilton-Shield (Bristol Children’s Hospital, U.K.); and Jill Clayton-Smith (Genetic Medicine, St. Mary’s Hospital, U.K.).

They state in the abstract to their Nature paper: “Obesity is a highly heritable and genetically heterogeneous disorder.”

Within the Genetics Of Obesity Study (GOOS), they analyzed the DNA for additions or deletions of chromosomes within 300 Caucasian children with severe early-onset obesity; that is, they weighed up to 220 pounds by the age of ten years.

Of the 300 children, 143 of them already possessed delay in their development.

Within these children, the researchers found large, rare deletions of chromosomes when compared to 7,366 control children.

In fact, in one such deletion, that of chromosome 16, the researchers found that such an absence causes the brain to be unable to respond to the hormone leptin, which controls appetite.

Page two quotes Dr. Farooqu with respect to what happens when children lack a particular chromosome.




Dr. I. Sadaf Farooqu, one of the authors of the study, stated that children with a chromosome 16 DNA deletion "have a very strong drive to eat.” She goes on to say, “They're very, very hungry, they always want to eat." [ABC News: “Study: Missing DNA Can Promote Childhood Obesity”]

According to the University of Cambridge website of Dr. Farooqu, “… we have identified patients with mutations in genes encoding leptin, the leptin receptor and targets of leptin action (including the melanocortin 4 receptor, MC4R). We have demonstrated that the central leptin-melanocortin axis plays a critical role in the regulation of human food intake.”

Although obesity in children has been linked to DNA in the past, this study associates childhood obesity to larger portions of DNA, those that extend over several genes.

For instance, the chromosome 16 deletion mentioned earlier, spans nine genes.

One of these genes, SH2B1, is known to play a critical role in regulating weight in humans.

In fact, they stated within their abstract, “We identified five patients with overlapping deletions on chromosome 16p11.2 that were found in 2 out of 7,366 controls…. In three patients the deletion co-segregated with severe obesity. Two patients harboured a larger de novo 16p11.2 deletion, extending through a 593-kilobase region previously associated with autism and mental retardation; both of these patients had mild developmental delay in addition to severe obesity.”

And, “In an independent sample of 1,062 patients with severe obesity alone, the smaller 16p11.2 deletion was found in an additional two patients. All 16p11.2 deletions encompass several genes but include SH2B1, which is known to be involved in leptin and insulin signalling. Deletion carriers exhibited hyperphagia and severe insulin resistance disproportionate for the degree of obesity.”

Page three concludes.




The researchers concluded, “We show that copy number variation contributes significantly to the genetic architecture of human obesity.”

The researchers are furthering their research in this area.

Dr. Farooqu states on her website, “We are currently using neuroimaging particularly functional MRI to study the brain response to hunger and satiety in defined subsets of patients with molecularly defined causes for their obesity.”

Learn more about childhood obesity at MyFamilyWellness.org and MayoClinic.com.

Find out more about many subject areas within childhood obesity at the Wikipedia.org website.

The article talks about numerous causes of obesity in children, including, diet, sedentary lifestyle, genetics, home environment, developmental factors, medical illness, and psychological factors.

The article includes this statement, "The first problems to occur in obese children are usually emotional or psychological. Childhood obesity however can also lead to life-threatening conditions including diabetes, high blood pressure, heart disease, sleep problems, cancer, and other disorders."

"Some of the other disorders would include liver disease, early puberty or menarche, eating disorders such as anorexia and bulimia, skin infections, and asthma and other respiratory problems."



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