Genetic Factors in Telomere Length
Human chromosomes are capped and stabilised by telomeres, which essentially act like the aglets on the ends of our shoelaces – preventing them from unravelling. Additionally, telomeres protect chromosome ends from being recognised as broken DNA by repair enzymes, and thus the accidental fusion of one chromosome to another.
Telomeres are predominantly formed from several thousand tandem repeats of a (TTAGGG)n DNA sequence motif. These repeat sequences are inefficiently replicated and so telomeres tend to shorten with each cell division, resulting in a progressive reduction in mean telomere length each year. This progressive shortening can be measured in DNA from our white blood cells and used, like a molecular clock, to estimate our biological age. Much research worldwide, including in this lab, is focused on factors that may make this “clock” run faster or slower in different people and whether critically short telomeres are predictive of the onset of diseases of aging, such as cancer and heart disease. It is believed that “stress factors”, such as cigarette smoking, may increase the rate of telomere shortening and thus speed-up this molecular clock.
We have developed a robust, high-throughput, RealTime PCR method for measuring mean telomere length in DNA from the white blood cells of study volunteers. We have been using this assay to test the hypotheses that mean telomere length is a heritable trait and that short telomeres are associated with increased susceptibility to common cancers. We are conducting experiments to find the genetic determinants of mean telomere length and, subsequently, whether genetic factors that tend to shorten telomeres also predispose to cancer and other diseases of aging.