Life expectancy is affected by the number of copies of genes
Variation in the number of copies of genes is the absence (deletion) of a particular DNA fragment or, conversely, the presence of an extra copy (duplication). Such anomalies are quite rare, but they often play an important role in the formation of an increased or reduced risk of developing various diseases.
Scientists at the Center for Applied Genomics, part of the Children's Clinic of Philadelphia, working under the leadership of Dr. Hakon Hakonarson, conducted the first genome-wide population study of variations in the number of copies of genes potentially associated with human longevity.
As part of their work, they compared variations in the number of gene copies, mainly found in the genomes of 7,313 patients of European origin in their clinic under the age of 18 and in the genomes of 2,701 Icelandic residents aged 67 and older, attracted by the Icelandic Association for the Study of the Heart. To conduct a genome-wide analysis of DNA samples to identify variations in the number of copies of genes, the authors used sets of microchips.
When analyzing the data obtained, the researchers proceeded from the assumption that variations in the number of copies of genes found only in children with health disorders requiring medical supervision are more likely to be associated with high risks of developing diseases, whereas variations in the number of copies of genes more common in elderly people, on the contrary, provide better health and accordingly, a longer life expectancy.
After conducting a similar study using DNA samples from an independent population of US residents, including 2,079 children and 4,692 elderly people, and making statistical adjustments to the structural features of all analyzed populations, scientists identified seven genes, the number of copies of which significantly differed in sick children and adolescents and practically healthy elderly people. Three of them are deletions of the DNA sequence, while the remaining four are duplications.
More than half of the genes affected by the identified mutations are involved in alternative splicing. This important biological mechanism lies in the fact that some genes have the ability not just to express one protein product, but, due to modifications of informational RNAs, to provide synthesis of various proteins encoded by the same DNA sequence.
The results obtained indicate that variations in the number of copies of genes, as well as other genetic variants, can control the biological functions of the body by influencing genetic mechanisms, such as alternative splicing. The authors note that there is still a lot of work ahead to study the mechanism they have uncovered, but they believe that variations in the number of copies of genes that occur mainly in children may be potential new targets that cause a short life expectancy. Perhaps, if the detection of such variations in the number of copies of genes is made a component of early clinical screening, they can become prognostic markers for identifying patients who need personalized preventive measures.
Article by Joseph T. Glessner et al. Copy Number Variations in Alternative Splicing Gene Networks Impact Lifespan is published in the journal PLOS ONE.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Children's Hospital of Philadelphia:
Gene Variants Found to Affect Human Lifespan.
06.02.2013