Variations in the incidence of schizophrenia: Data versus dogma

The schizophrenia research community has shared a belief that the incidence of schizophrenia shows little variation. This belief is related to the dogma that schizophrenia affects all individuals equally, regardless of sex, race, or nationality. However, there is now robust evidence that the incidence of schizophrenia is characterized by substantial variability. There is prominent variation in the incidence of schizophrenia between sites. The incidence of schizophrenia is significantly higher in males than in females (male:female ratio = 1.4). Migrants and those living in urban areas have a higher incidence of schizophrenia. The incidence of schizophrenia has fluctuations across time. In addition, the prevalence of schizophrenia is also characterized by prominent variation. The realization that schizophrenia is characterized by rich and informative gradients will serve as a catalyst for future research.

Rapid screening of 4000 individuals for germ-line variations in the BRAF gene

Background: The BRAF gene is frequently somatically altered in malignant melanoma. A majority of variations are at the valine 600 residue leading to a V600E substitution that constitutively activates the kinase. We screened 4000 patient and control DNAs for germ-line variations at the valine 600 residue. Methods: We developed a novel assay by adapting single-base variation assays and software for MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry to screen for all 5 reported variants at codon 600 of the BRAF gene. We screened a case-control collection comprising samples from 1082 melanoma patients and 154 of their unaffected relatives from 1278 families and from 2744 individuals from 659 unselected twin families with no history of melanoma. A panel of 66 melanoma cell lines was used for variation-positive controls. Results: All melanoma cell lines that we had found previously to carry a codon 600 variation were verified in this study. Three of the 4 possible variants (V600E n = 47, V600K n = 2, V600R n = 1) were detected, but no case of V600D was available. No germ-line variants were found in the samples from the 3980 melanoma patients or from the control individuals. Conclusions: This new assay is a high-throughput, automated alternative to standard sequencing and can be used as a rapid initial screen for somatic variants associated with melanoma. Germ-line variants at valine 600 are unlikely to exist and do not contribute to the reported role of the BRAF gene in melanoma predisposition. (c) 2006 American Association for Clinical Chemistry.