By comparing the DNA of children to that of elderly people, genetic researchers have identified gene variants that influence the lifespan by either raising the risk of disease or by providing protection from disease.
Study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, said of the study, hwich was published in the Jan. 30 edition of the journal PLoS ONE:
"This research is the first genome-wide, population-based study of copy number variations in children associated with human longevity."
Copy number variations, or CNVs, are losses or gains in DNA sequence that are usually rare, but often play an important role in raising or lowering the risk of disease. For the study, the researchers compared the rates of CNVs in a sample of 7,313 subjects under the age of 18 from the Children's Hospital network to a a group of 2,701 Icelandic subjects aged 67 years old or above that were recruited by the Icelandic Heart Association. The scientists used microchip arrays to perform the whole-genome CNV analyses.
Hakonarson said that they assumed that CNVs appearing in children, but not in the elderly were more likely to be disease-causing, while CNVs that were proportionately higher in the elderly were more likely to be protective, which would allow them to live longer.
After performing a replication study in an independent U.S. cohort of 2,079 children and 4,692 older people and making statistical adjustments to address population stratification, the researchers found seven significant CNVs.
Three of the CNVs were deletions of DNA sequence, and four were duplications. The genes that were impacted by the CNVs disproportionately involved alternative splicing, which is an important biological mechanism in which instead of one gene simply expressing one protein, modifications to messenger RNA result in different protein products based on the same underlying DNA code in a given gene.
The CNVs found to be overrepresented in children may represent novel targets implicated in short lifespan. Hakonarson said that if such CNVs are incorporated into early clinical screening tests in the future, their presence could be prognostic markers indicating which patients should take individualized preventative health measures.