Paternal Age and Epigenetics Why One Twin Can Be Affected and Not the Other

Geneticists have also been unable to explain why identical twins sometimes aren't. Born of the same egg and sperm, the twins' genetic blueprints couldn't be more similar. Yet physicians have known for decades that one twin can become chronically ill while the other carries on in perfect health. If one identical twin is autistic, for example, the other often is, too, but only in 60 percent of the cases. For people with schizophrenia and bipolar disorder, two debilitating mental illnesses, the rate for their identical twins hovers near 50 and 75 percent.

Doctors have explained this twin paradox by saying something in the environment – a virus, say, or stress – triggers disease in one twin but not the other. But decades of searching hasn't turned up convincing triggers.

Enter epigenetics. What if, scientists are asking, chemical flags settle on one twin's DNA but not the other's? If these flags are sprinkled on or stripped from a gene that's critical for brain development, could autism or schizophrenia develop?

Epigenetically unique
The scientists scrutinized the epigenetic flags on a gene implicated in schizophrenia. In the pair who both had the disease, the scientists noted similar epigenetic patterns. In the other pair, the twin who had schizophrenia was epigenetically more similar to the first pair than to the sibling. It could be that the "sick" epigenetic pattern is contributing to schizophrenia, Petronis said. Even if that's not the case, he said, the study shows that two people who are genetically matched can be epigenetically unique.


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Thursday, August 23, 2007
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.
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"Pediatricians will call me and say this is cool," said Rockefeller's David Allis. "One identical twin will be hugely normal and the other will be hugely autistic. What gives? The biology tells us that the kids are really genetically matched sets."

There's still no proof that epigenetics is behind identical twins' differences. But it's such a logical explanation, researchers argue, it's worth investigating.

A recent study by Petronis and colleagues, for example, shows that genetically identical twins can differ epigenetically. This year in Schizophrenia Bulletin, the scientists reported on a study of two pairs of identical twins. In one pair, both twins had schizophrenia. In the other pair, only one did.