Genome sequencing is changing its approach to focus more on rare conditions affecting individuals instead of common population-wide diseases. Scientists are abandoning genome-wide association studies (GWAS) which focus on DNA analysis of common diseases and which have been the aim of genomics research in the last decade. They are instead returning to study rare disorders which are traceable to defects in single genes.
'The issue is how we're going to understand the architecture of common disorders', says Richard Gibbs, director of the Human Genome Sequencing Center at Baylor College of Medicine in Houston, Texas, US, adding: 'Three or four years ago I thought it was going to be because of GWAS studies, but I now think that we're going to get there by understanding a whole lot of these Mendelian diseases.'
GWAS studies examine the DNA of thousands of unrelated people with common diseases, however, breakthroughs from this type of study have been slow to materialise. The cost of sequencing whole genomes is now dropping and the benefit of extracting information in this way is the availability of in-depth information about individuals, enabling scientists to find the exact gene mutation underlying rare diseases. This change in approach to genomics was revealed at the second Personal Genomes meeting held in New York in September. Where traditional genomics research has centered on high-profile diseases such as cancer, a shift toward targeting more unusual disorders is now evident.
Gibbs reports that together with his colleagues at Baylor, he has sequenced the genomes of one family with a familial neuropathy (a disease which causes muscle weakness and pain) pinpointing a single gene which is very likely to be responsible for the family's condition.
Elsewhere in the US, examples of individually-focused research is already underway. Genetic scientist Richard Lifton (Yale University) was asked to study the DNA of an ill child who presented with symptoms of kidney disease including hourly diarrhoea. Having sequenced the exomes of the child and several of his family members, a variant of the gene SLC26A3 which causes congenital chloride diarrhoea, was discovered.
One group of collaborators working at Complete Genomics in California announced recently that it will offer complete human genome sequencing next year for $5,000, making public access to these services easier, but alarming fellow researchers. Elaine Mardis, a director of the Genome Sequencing Center at Washington University in Missouri warns that error rates are still high and the public should be wary of a service which seems accessible but could be very costly to verify.