Scans of the entire human genome turn up genes involved in common diseases.

A number of recent studies have identified genes involved in common disorders, including obesity, diabetes, and heart disease. Researchers used gene chips to scan hundreds of thousands of DNA variations across thousands of individuals to find changes associated with the disorders.

"A Common Variant in the FTO Gene is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity" by Timothy M. Frayling and others, Science (volume 316), May 11, 2007, pages 889-894.

"A Common Allele on Chromosome 9 Associated with Coronary Heart Disease" by Ruth McPherson and others, Sciencexpress May 3, 2007 (published online 10.1126/science.1142447).

"A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction" by Anna Helgodottir and others, Sciencexpress May 3, 2007 (published online 10.1126/science.1142842).

"Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels" by Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research, Sciencexpress April 26, 2007 (published online 10.1126/science.1142358).

"A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants" by Laura J. Scott and others, Sciencexpress April 26, 2007 (published online 10.1126/science.1142382).

"Replication of Genome-Wide Association Signals in U.K. Samples Reveals Risk Loci for Type 2 Diabetes" by Eleftheria Zeggini and others, Sciencexpress April 26, 2007 (published online 10.1126/science.1142364).

Duration: 3 minutes, 28 seconds

Posted: May 18, 2007

Jan Witkowski: Welcome to DNA Today, I'm Jan Witkowski...

Dave Micklos: …and I'm Dave Micklos. We're here at Cold Spring Harbor Laboratory discussing news about DNA.

JW: Today our news comes not from just one paper but from 9 papers, reporting discovery genes in 5 disorders: diabetes, obesity, prostate cancer, coronary heart disease...

DM: I think you are close enough. But you know, beginning in the 1980's, scientists were successful at isolating disease, genes behind rare disorders, like neurofibromatosis, cystic fibrosis and Duchenne muscular dystrophy. This involved taking family members and comparing their DNA and looking for differences between normal and affected members of the family.

JW: It's been much more difficult to find genes involved in common diseases – common complex diseases like schizophrenia or diabetes. This is because… for 2 reasons. One is that it's thought that there are many genes involved in these disorders – any one which only tribute a little bit to disease. Secondly, their interactions with the environment – diet and stress and so on. Family studies can't be used in these disorders. So how did the studies find these genes?

DM: They use a new method call whole genome association where they look for differences across the entire genome – that's the whole set of human chromosomes. What they were looking for were differences in single nucleotides called single nucleotide polymorphisms – or SNPs. Now, these amount to single letter changes in the DNA alphabet of A, T, C, and G. Behind us we see a sequence of DNA, and this would be a SNP in one of our smallest chromosomes, where some people may have a C at this position and others may have a T. The trick was to scan for hundreds of thousands of these single nucleotide polymorphisms across the chromosomes of tens of thousands of people. This takes gene chips to do.

JW: As Dave just said, you do these studies not within families but simply by taking lots of people who are affected, and compare their DNA with DNA from lots of people who are unaffected. And by “lots”, we really do mean lots. The Coronary heart disease study, for example, examined DNA from over 40,000 individuals. You need to do this because these studies are not very sensitive, so you need large number to get statistical significance. They found interesting things. The diabetes study found nine genes that played a part in diabetes.

DM: Yes, and one of these genes was in fact a gene call FTO – I have no idea what that stands for – but it's not only related to diabetes, but to the body mass index. This is a measure of body fat takes into account on your height and your weight. I happened to check my body mass index and mine is quite good, it is 23.9, which is in the normal range. So I would presume that have two good copies of the FTO gene. How about you?

JW: .. I think I am going to keep mine secret.