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Schizophrenia as variation in the sapiens‐specific epigenetic instruction to the embryo
Author(s) -
Crow TJ
Publication year - 2012
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2012.01830.x
Subject(s) - biology , genetics , homo sapiens , epigenetics , evolutionary biology , gene , anthropology , sociology
Crow TJ. Schizophrenia as variation in the sapiens‐specific epigenetic instruction to the embryo. The psychoses (schizophrenia and bipolar disorder) occur in all populations with approximately uniform incidence and sex‐dependent age of onset. Core symptoms involve aspects of language; brain structural deviations are sex and hemisphere‐related. Genetic predisposition is unaccounted for by linkage or association. The hypothesis is proposed that the ‘missing heritability’ is epigenetic in form and generated in meiosis on a species‐specific XY chromosomal template. A duplication from Xq21.3 to Yp11.2 that occurred 6 million years ago is proposed as critical to hominin evolution. Within this block of homology the Protocadherin11XY gene pair is expressed as a cell surface adhesion factor in both X and Y forms; it has undergone a series of coding changes (16 in the Y sequence and 5 in the X including two to cysteines) in the hominin lineage. According to the hypothesis these sequence changes, together with one or more deletions and a paracentric inversion in the Y block, were successively selected; late events in this series established cerebral asymmetry (the ‘torque’) as the defining characteristic of the human brain. Built around this reference frame, an epigenetic message channels early development of the embryo in a sapiens‐specific format. Diversity in meiotic pairing is postulated as the basis for species‐specific deviations in development associated with psychosis.