Genetic basis of schizophrenia: Trinucleotide repeats - An update

1. Recent developments in technologies permit systematic screening of the e ntire human genome as a strategy for identification of susceptibility genes of small effect that influence risk to complex traits, like schizophrenia (Schz), inflammatory bowel disease, bipolar affective disorder (BPAD) etc. 2. Schizophrenia is known to have a high heritability and a complex inherit ance pattern. Several studies provide evidence that both genes acid environ ment play a role in the etiology of schizophrenia. Linkage studies have obs erved racial and sex bias in the genetic constitution of schizophrenia. Sch izophrenia also manifests clinical anticipation and genomic imprinting. 3. "Dynamic mutations" or "tandem repeat expansions" in DNA, explain a numb er of observations associated with clinical anticipation and genomic imprin ting. In patient populations, the repeat expands well beyond the normal ran ge, altering the biological function of the gene. These sequence are unstab le and increase in size between family members in successive generations, g iving rise to greater severity of disease. 4. Several workers have reported an association of trinucleotide repeat len gth with adult- and child-onset schizophrenia. One such expanded allele has been found at the CTG18.1 locus on the 18th chromosome. Other genes known to have similar mutation are SEF2-1, which codes for a helix-loop-helix pro tein, hSKCa3 gene, which codes for a calcium- activated potassium channel a nd the transthyretin gene. Ln schizophrenic patients, significant differenc e in allele frequency distribution of these genes has been reported. 5. Population based genetic research would not only help identify different subgroups of this of schizophrenia.