The state of the art technique for finding low frequency/rare genetic variants relies on next generation sequencing technologies to undertake whole exome sequencing. The GOOS laboratory research team has been at the forefront of such emerging technologies for gene discovery. Whole exome capture coupled with high throughput sequencing provides sequence on all 19,000 genes that code for proteins.
Recently, we have completed a whole exome sequencing study in 1000 patients from GOOS. This study was performed in collaboration with the UK10K consortium, in which we play a major role, to identify rare variants in health and disease (www.uk10k.org). In order to manage the large amount of data produced from whole exome sequencing, we adopted a strategy that allowed us to interrogate new and known obesity genes. We are now performing further association analyses to search for new obesity-associated genes.
In these areas, we collaborate with Dr Ines Barroso at the Wellcome Trust Sanger Institute, located just outside Cambridge which is one of the major centres for genetics research in the world.
We have also embarked upon a case control association study in people with a low BMI to study the genetics of thinness. STILTS (STudy Into Lean and Thin Subjects) will allow us to investigate genes and pathways that play a role in thinness, which is as highly heritable as severe obesity.