A meta-analysis of twin selleck chemical Bortezomib studies estimated the heritability to be 81% (confidence interval 73% to 90% )3 and a recent Swedish study of more than 2 million families
estimated it to be 64%. 4 Of all the known risk factors for schizophrenia, genetics is the single largest one. No precise mode of inheritance is known, and less than one third of patients with schizophrenia have a family history. Elucidation of etiological factors remains the overwhelming challenge Inhibitors,research,lifescience,medical to schizophrenia researchers. In fact, the most effective method for identification of genetic risk factors for schizophrenia is not clear, and this has led to a number of approaches, including epigenetics, being adopted, in an attempt to clarify the genetic etiology. Since the initial observation that schizophrenia has a polygenic Inhibitors,research,lifescience,medical mode of inheritance and availability of polymorphic markers for genetic mapping, many attempts have been made to find susceptibility genes for schizophrenia using either the methods of linkage or association.5,6 One of the early strategies used to begin unraveling the genetic contribution of schizophrenia was the investigation of chromosomal aberrations and familial syndromes with schizophrenia-like phenotypes. Chromosomal aberrations have been reported in families with schizophrenia and other psychiatric disorders.7,8 The
deletion of a section of 22q11 leads to the phenotype Inhibitors,research,lifescience,medical of velocardiofacial (DiGeorge) syndrome that includes abnormalities in facial features, the palate, Inhibitors,research,lifescience,medical and midline heart defects. Patients with 22q11 deletion syndrome exhibit psychotic symptoms resembling schizophrenia at a frequency of 18%, a rate that is much higher than the overall 1% prevalence of schizophrenia in the general population. On the other hand, when focusing on populations of patients who have the diagnosis of schizophrenia, at least 2% of these individuals are reported to have 22q11 deletions compared with the 0.025% prevalence Inhibitors,research,lifescience,medical in the general population.9,10 This region of 22q11 harbours
the COMT and PRODH genes among others (Table I). Table I Some schizophrenia candidate genes and their association with schizophrenia according to chromosomal location, genetic association, biology/animal models, expression alterations, and meta-analysis results. The number of “+” indicates the … A AV-951 number of other chromosomal aberrations have been associated with schizophrenia. On chromosome one, a balanced (1;11)(q42.1;q14.3) translocation, which disrupted the DISC1 gene (Table I), was found in a large Scottish family with high frequency of psychiatric disorders including schizophrenia.22,56,57 More recently, another family of mother-daughter pair with schizophrenia was identified with t(9;14)(q34;q13) translocation which disrupts the NPAS3 (neuronal selleck Dorsomorphin Period Aryl hydrocarbon receptor Single-minded) gene,58,59 that codes for a transcription factor implicated in neurogenesis.