JERUSALEM, Aug 1 – Israeli genomics company IDGene Pharmaceuticals said Wednesday it has found further evidence to support the study of homogenous populations as a way of determining the genetic basis of disease.
In an article published this week in Nature Genetics , IDGene’s CEO, Ariel Darvasi, and Sagiv Shifman, of Hebrew University’s Department of Evolution Systematics and Ecology, assert that in a study of the Ashkenazi Jewish population they found a significantly greater level of linkage disequilibrium particularly for SNPs located at relatively big distances from one another.
"There has been a dispute in the literature regarding the advantage of using isolated populations and the claim was that for common variants the linkage disequilibrium was not that great," Darvasi told GenomeWeb.
"We found that along small distances between SNPs there is no difference between two populations, but when you start having SNPs separated a bit more there is a five- to seven-fold increase in favor of the isolated populations," Darvasi said.
In their study, the authors said they also found that the background noise decreased significantly in the homogenous population.
Darvasi said his findings go one step further than recent research conducted by Eric Lander to demonstrate that the significance of linkage disequilibrium increases with the homogeneity of a population.
"In the Lander paper, they looked at two populations, Caucasians and Africans, and determined the linkage disequilibrium between the two. With the Ashkenazi population we are even one step ahead of that," said Darvasi.
In May, Lander, director of the Whitehead Institute Center for Genome Research, published a paper in Nature demonstrating that in 19 randomly selected regions of SNPs along the human genome, linkage disequilibrium in a group of Americans of north-European descent typically extends 60 kilobases from common alleles versus less than five kilobases for a Nigerian population.
Some researchers have warned, however, that linkage disequilibrium can vary along different regions of the genome and have cautioned that the bigger the linkage disequilibrium the harder it can be to pinpoint the gene.
Darvasi said he planned to compensate for the latter effect by using large sample sizes, which would help provide good mapping resolution for the specific regions of interest. He said IDGene would also use samples from other non-Ashkenazi populations to validate the findings.
"With our samples we can make the discoveries faster and then we can validate the results using samples from other populations," he said.
Darvasi added that he is confident the current research further supports IDGene's approach, which he expects will eventually reap rewards in the form of new and better treatments.
IDGene is currently applying its findings to study the genetic basis for a variety of diseases, including type 2 diabetes. So far, the company has collected 10,000 DNA samples from Israel’s Ashkenazi population, which dates back 500 years to Germany. Ashkenazi Jews comprise about half of Israel’s five million Jewish citizens.
Using Pyrosequencing’s technology, IDGene is generating genetic profiles based on specific regions of the genome it believes play a crucial role in the diseases of interest. The company is using publicly available data on the mouse to help identify these regions.
Darvasi said he was currently evaluating other companies’ technologies in order to increase throughput. In addition to looking at Pyrosequencing’s 384 wellplate system, Darvasi said he was also considering buying systems from Qiagen, Sequenom, Orchid Bioscience, and Applied Biosystems.
The company, which currently has 40 employees, has so far raised $10 million in venture capital. Darvasi said he expects to raise another round of financing during the last quarter of this year or the first quarter of 2002.