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Frans EM, McGrath JJ, Sandin S, Lichtenstein P, Reichenberg A, Långström N, Hultman CM. Advanced paternal and grandpaternal age and schizophrenia: a three-generation perspective. Schizophr Res . 2011 Dec ; 133(1-3):120-4. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Michael O'Donovan, SRF Advisor
Submitted 24 October 2011 Posted 25 October 2011
  I recommend this paper

A useful addition to the literature on parental age and schizophrenia, and the possibility this might reflect de-novo mutations.

View all comments by Michael O'Donovan

Comment by:  Timothy Crow
Submitted 26 October 2011 Posted 27 October 2011
  I recommend this paper

In agreement with Mick O'Donovan, but for further reasons I recommend this paper. The authors point out that the pattern of transmission is consistent with X linkage. On this assumption, to account for the fact that the well-established paternal age effect applies to sons as well as daughters, one must also postulate Y linkage. This is consistent with the hypothesis that an X-Y linked gene plays a significant role in predisposing to psychosis. In this respect, the Protocadherin11XY gene-pair has a relevant history, as it was established by an X to Y duplication early in hominin evolution, and has been subject to subsequent change (16 coding substitutions in the Y and 5 in the X sequence). But if relevant, I expect the variation to be epigenetic rather than sequence based, for reasons associated with the role of the sex chromosomes in relation to species-defining characteristics.


Crow TJ (2002) Handedness, language lateralization and anatomical asymmetry: relevance to hominid speciation and the etiology of psychosis. Brit J Psychiat 181: 295-297. Abstract

Williams NA, Close J, Giouzeli M, Crow TJ. (2006) Accelerated evolution of Protocadherin11XY: a candidate gene-pair for cerebral asymmetry and language. Amer J Med Genet, NPG, 141B: 623-635. Abstract

View all comments by Timothy Crow

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