Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease

The Metabolic Syndrome is one of the most prevalent polygenic disorders, affecting about 20 million people in Germany and as many as 47 million in the United States. Comprised of a cluster of disorders of the body's metabolism, the clinical markers include obesity, hypertension, insulin resistance, and dyslipidemia. As a result, affected persons have a higher risk of developing type II diabetes, heart disease, or stroke.

Now, using expression profiling in a genome-wide screen, linkage analysis, and comparative mapping techniques, Norbert Hübner and colleagues have identified 73 candidate genes for hypertension in humans. (Nature Genetics , online doi: 10.1038/ng1522). Using a BXH/HXB panel of recombinant inbred (RI) rat strain which mimics the human metabolic syndrome, the researchers analyzed genome-wide expression data of almost 16,000 transcripts generated from fat and kidney tissues of 30 RI strains. The study detected cis- and trans- acting quantitative trait loci (called eQTLs) and showed that gene expression is regulated in cis by many of the eQTLs as a monogenic trait. Mining of this data should lead to new insights into the genes and regulatory pathways involved in metabolic and cardiovascular diseases.

Contact

Pamela Cohen
p.cohen@mdc-berlin.de
+49 30 9406 2121