A study published in the journal Nature this past week provides evidence that paternal age is correlated with autism and schizophrenia. There are multiple interesting nuances from the study. Below I mention a few. But first a little background . . . .
DNA provides a manual for how a single fertilized egg will grow into a person. If the ‘text’ of the ‘manual’ contains errors, either it is inconsequential or it will result in changes as the embryo/fetus/person develops. (Normally, therefore, one would think of these errors, or mutations, as undesirable, though it must be remembered that some errors produce positive change resulting in the benefits of evolution). At birth, a baby girl already has all the eggs she will ever possess. A baby boy however, has no sperm. Sperm production begins at puberty (it takes about two weeks to produce sperm) and continues throughout the remainder of a man’s life. So over many years, there are lots of rounds of sperm production, with each cycle having the potential for a mutation to occur.
So . . . the interesting findings from the study are:
1) Mutations arising from the eggs (Mom’s side) tend to number approximately 14, and this is constant regardless of maternal age. [Note that conditions like Down syndrome, which are related to maternal age, occur because of problems with cell division as eggs age, which is different from the number of mutations at individual points along the genetic/DNA code.]
2) Mutations from Dad’s side average about 55 in number. The number of paternal mutations doubles every 16.5 years. For context, there are about 60 mutations in sperm from a 28 year old, 75 mutations from the sperm of a 36 year old, and 120 mutations from the sperm of a 45 year old man. Most mutations (maternal and paternal) are not harmful.
3) Schizophrenia and autism are poorly understood and have multi-factorial causes. The higher rates of mutations seen with increasing paternal age only explain 20-30 percent of the cases of these conditions, as suggested by the baseline rates seen with younger parents and also by genetic patterns observed in studies (schizophrenia is known to have a familial pattern, with stronger association of the disease on the father’s side).
A final note . . . this study was done by researchers at deCODE genetics. This company has compiled an impressive genetic and genealogical database across the population of Iceland. Because Iceland is both homogenous and historically isolated (and because the Icelandic people placed an importance on keeping rich, detailed genealogy records), deCODE has a unique ability to look at occurrences of disease in this population and identify common mutations which are likely to be implicated as positive. This, along with the detailed genome mapping that is now being undertaken at academic centers to better understand disease, should hopefully advance science and provide new avenues for drug development.