title: Where and what is the right shift factor or cerebral dominance gene? A critique of Francks et al. (2007).
abstract: Francks et al. (2007, p. 1129) claim to have identified "The first potential genetic influence on human handedness ... and the first putative genetic effect on variability in human brain asymmetry" and a gene "that underlies much of human cognition, behaviour and emotion" (p. 1129). We criticise this claim on the basis that the authors have made unjustified assumptions concerning mode of transmission both of psychosis and relative hand skill, that they have failed to establish a parent of origin effect, and have overlooked previous findings concerning the genetic basis of handedness and asymmetry. We suggest that some of these errors relate to the application of linkage disequilibrium to detect variation that is common in the population and relates to the characteristic that defines the species. While we agree (and indeed first proposed) that the variation underlying psychosis is intrinsically related to the cerebral torque, which we take to be the anatomical basis of language, we are unconvinced by the data for LRRTM1 presented by Francks et al. We consider that a stronger case can be mounted for the Protocadherin11X/Y gene pair located in the hominid specific Xq21.3/Yp11.2 region of homology that was generated by a duplication from the X between 6 and 5 million years ago and that has been subject to a number of chromosomal and sequence changes. This gene pair can account for relationships between relative hand skill and verbal and non-verbal ability that are sex dependent, and morphological changes in the brain in psychosis that reflect interactions between sex and laterality, which are already established in the literature.
authors.affiliation: Warneford Hospital, Oxford, UK. tim.crow@psych.ox.ac.uk
authors.forename: T J
authors.initials: TJ
authors.lastname: Crow
authors.forename: J P
authors.initials: JP
authors.lastname: Close
authors.forename: A M
authors.initials: AM
authors.lastname: Dagnall
authors.forename: T H
authors.initials: TH
authors.lastname: Priddle
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015820:Cadherins / Q000235:genetics*; D004292:Dominance, Cerebral / Q000235:genetics*; D007839:Functional Laterality / Q000235:genetics*; D015186:Hominidae; D006801:Humans; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000091363:Protocadherins; D011618:Psychotic Disorders / Q000235:genetics*
chemical_list: D015820:Cadherins; C526971:LRRTM1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C404498:PCDH11X protein, human; C468654:PCDH11Y protein, human; D000091363:Protocadherins