NOVEL MUTATIONS IN THE PROMOTER AND CODING REGION OF THE HUMAN 5-HT1ARECEPTOR GENE AND ASSOCIATION ANALYSIS IN SCHIZOPHRENIA

Dysfunction of serotonin systems has been implicated in schizophrenia, In the present study, the human 5-HT1A receptor gene containing the 5 ' untranslated region was screened in order to detect genetic variatio ns, through which alteration of protein function or level of expressio n might contribute to schizophrenia. Genomic DNAs were isolated from w hole-blood samples of 61 unrelated schizophrenic patients and 100 heal thy controls. Genetic variations were screened systematically by singl e-strand conformational polymorphism (SSCP) analysis, followed by dire ct sequencing of polymerase chain reaction (PCR) product as well as re striction fragment-length polymorphism (RFLP), The novel mutations (-5 1T --> C, -152C --> G, -321G --> C, -480delA, and -581C --> A) were fo und in the 5' untranslated region. Furthermore, we found a novel misse nse mutation (Gly272Asp) in the coding region in addition to the mutat ions (Pro16Leu, 294G --> A, and 549C --> T) reported previously. No si gnificant differences in genotype frequencies as well as allele freque ncies were found between patients and controls. Our data provided no e vidence of association between schizophrenia and the variants in the 5 ' untranslated region as well as the coding region of the human 5-HT1A receptor gene. (C) 1998 Wiley-Liss, Inc.