Guest Post by Kevin Smith
It is well known that the risk of disorders resulting from chromosomal abnormalities, such as Down’s syndrome, correlates with advancing maternal age. Less widely known is the correlation between the age of fathers and an increased risk of a range of disorders in their resultant offspring, the most prominent of which are neuropsychiatric conditions including schizophrenia and autism. This is the paternal age effect, the importance of which has recently become clear through a growing body of molecular genetic and epidemiological data.
The paternal age effect results from new mutations occurring in the stem cells from which sperm cells are derived, resulting in an accumulating mutational burden as the male ages. Genetic abnormalities resulting from these paternal mutations are usually subtle at the molecular level (involving as little as a single nucleotide change), highly heterogeneous, and do not usually result in detectable foetal abnormalities. Accordingly, the opportunity for prenatal detection of such cases is very limited. (By contrast, the genetic abnormalities associated with maternal aging typically involve substantive chromosomal aberrations, comprise a relatively restricted range of commonly occurring forms, and frequently produce marked foetal defects; these features ensure that routine screening and testing reveals the majority of such cases prior to birth, permitting termination of affected foetuses.) Additionally, and again in contrast to genetic aberrations associated with maternal age, paternal de novo mutations are transmitted through successive generations of males, with a concomitant intergenerational accumulation of genetic abnormalities. Moreover, at least in Western societies, the average age of fatherhood is increasing markedly, a situation that will increase the burden of these mutations.
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