NEW PAPER Older Paternal Age and Schizophrenia, CNVs, Point Mutations,Dysregulation of Epigenic Factors, Chromosome Breakage

Schizophr Bull. 2007 Aug 21; [Epub ahead of print]
Aberrant Epigenetic Regulation Could Explain the Relationship of Paternal Age to Schizophrenia.
Perrin MC, Brown AS, Malaspina D.
2Department of Psychiatry, School of Medicine, New York University, New York, NY.
The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age and schizophrenia. Evidence suggests that advancing age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors.
PMID: 17712030 [PubMed - as supplied by publisher]








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Would Dr. Malaspina think that Dr. Wigler has a valid basis for this statement? Would she, as a pre-eminent researcher find the comparison between Down syndrome which is only 50% based on the age of the mother and autism misleading?


"Almost all cases [of spontaneous mutations] happen in the mother and are transmitted by the mother," he said, adding that the trait for Down is transmitted at the moment of conception. The trait is not hereditary in the same sense a "disease gene" is transmitted from one generation to the next.

"As people age, their genes increasingly acquire mutations that are not fixed through DNA repair mechanisms. That's why a spontaneous strike can lead to Down syndrome. And that is also why autism can similarly occur through CNVs, Dr. Wigler said.
"The older the mother, the more likely she has acquired spontaneous mutations" in her chromosomes, and will transmit them at conception, Dr. Wigler said. Less frequently, but just as likely, Dr. Wigler said, fathers can transmit autism traits as well."