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Ishizuka K, Paek M, Kamiya A, Sawa A. A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions. Biol Psychiatry . 2006 Jun 15 ; 59(12):1189-97. PubMed Abstract

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Comment by:  Judith Gault
Submitted 24 January 2007 Posted 25 January 2007
  I recommend this paper

When identifying causative genes in Mendelian diseases, the focus is on the identification of mutations that clearly disrupt the gene in more than one family and co-segregate with disease. Importantly, implicating mutations are not found in the general population. DISC1 is promising in this regard. Two different DISC1 mutations have been identified that are predicted to disrupt the protein in two families. The mutations are not found in the general population. There appears to be clinical heterogeneity and reduced clinical penetrance in the two families described with mutations.

Identifying more of these types of mutations in additional families is important and provides unbiased evidence that mutations in the “candidate” actually cause disease, although other types of variants like missense mutations found in affected and unaffected populations may contribute to disease. These types of mutations are much less convincing, especially in the absence of obvious mutations that disrupt the gene and co-segregate with disease. Positive linkage and association studies only...  Read more

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