Human Gene Knockouts Predict Disease Risk

Researchers have used “knockout” mice for decades to study how loss of gene function contributes to diseases. Recently, researchers at the University of Texas Health Science Center (UT Health) at Houston have investigated this gene-disease relationship using naturally occurring “knockout humans.”

Unlike mice, which are genetically engineered in the laboratory to possess certain mutations, the UT Health researchers sequenced the exomes of 8,554 individuals who participated in the Atherosclerosis Risk in Communities, a study conducted by the National Heart, Lung, and Blood Institute. The researchers looked for 20 phenotypes of risk factors related to chronic diseases and identified eight new relationships between gene variants and diseases. Notably, they showed that a heterozygous form of the gene TXNDC5 was related to progression of type 1 diabetes and elevated fasting glucose, and that individuals with a mutation in the SEPT10 gene had significantly reduced lung function.

Although senior author Eric Boerwinkle, PhD indicates further research is needed to determine the gene-disease relationship, he indicated that the data from the current study highlighted the potential utility of functional-variant annotation for assessing disease risk and response to drug therapies.

Read more: Li AH et al. Analysis of loss-of-function variants and 20 risk factor phenotypes in 8,554 individuals identifies loci influencing chronic disease. Nature Genetics, 2015 Mar 12

Source: Science Daily