A Systematic Approach to Mapping Recessive Disease Genes in Individuals from Outbred Populations

2009

Mapping Disease Genes in Outbred Populations

Sample size: 72 publication 10 minutes Evidence: high

Author Information

Author(s): Hildebrandt Friedhelm, Heeringa Saskia F., Rüschendorf Franz, Attanasio Massimo, Nürnberg Gudrun, Becker Christian, Seelow Dominik, Huebner Norbert, Chernin Gil, Vlangos Christopher N., Zhou Weibin, O'Toole John F., Hoskins Bethan E., Wolf Matthias T. F., Hinkes Bernward G., Chaib Hassan, Ashraf Shazia, Schoeb Dominik S., Ovunc Bugsu, Allen Susan J., Vega-Warner Virginia, Wise Eric, Harville Heather M., Lyons Robert H., Washburn Joseph, MacDonald James, Nürnberg Peter, Otto Edgar A.

Primary Institution: University of Michigan School of Medicine

Hypothesis

Can SNP arrays systematically allow gene identification by homozygosity mapping in single individuals from non-consanguineous populations?

Conclusion

Homozygosity mapping can effectively identify disease-causing mutations in single individuals from outbred populations.

Supporting Evidence

93% of cases had the causative gene positioned within a consistent ZLR peak of homozygosity.
The method allows for the detection of homozygous mutations in single cases from outbred populations.
Homozygosity mapping can reduce the complexity of gene discovery from thousands of genes to just a few.
Segments of homozygosity as short as 2 Mb can contain an average of only 16 candidate genes.
Most pediatric specialty clinics have access to cohorts of individuals from outbred populations.

Takeaway

Scientists found a way to find genes that cause diseases by looking at DNA from people who aren't closely related, which helps them discover new disease genes faster.