genes, disease liability, genome wide association, diabetes

In 1913, RA Fisher, an evolutionary biologist and pioneer of modern statistics, published a paper on the genetic causes of dis­ease that brought together two rival factions.
1. Geneticists who proposed a theory that diseases worked like Mendel’s pea plants, with just one or two genes responsible for each condition.
2. Biometricians, however, advocated a continuous distribution of phenotypes.
Fisher suggested that many mendelian traits could result in the continuous distribution of a disease.
But Fisher’s theories had been difficult to substantiate. Even the much-heralded Human Genome Project in the 1980s didn’t help as much as expected.
The two methods traditionally used to hunt down disease genes are linkage analysis, which uses large family trees to work out which genes are shared by affected individuals, and the candidate-gene approach, which uses physiological clues to narrow down potential culprits. But when it comes to complex conditions such as heart disease or diabetes, in which multiple environmental and genetic factors combine, neither method is very powerful- Scientists have identified just a handful of disease genes, along with lots of weak, unconfirmed hits.
Modern gene-chip technology combined with recently published maps of human genetic variants that groups together related variants single nucleotide polymorphisms enables the entire genomes of thousands of people to be scanned The GWA approach ( genome wide association )
Yet new results, including a stud)- en type 2 diabetes published this week (R. Sladek et al. .(Nature doi :10.1038/nature05616;2007 ) suggest that the GW’A approach will bear fruit, and lots of it This study on large numbers of type 2 diabetics and normals show . four genomic regions that confer a significant risk to developing the disease. Along with the pre­viously identified TCF7L2 gene, these regions together account for 70% of the genetic risk for the disease.
Of the four new genes, the best hit is SLC30A8, a zinc transporter, which is important because zinc assists with insulin secretion
Other diseases in the pipeline include coronary heart disease and rheumatoid arthritis.
Gene Russo Nature vol 445, 15 February 2007 pp 688-9

Martin Eastwood
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