title: Identification of novel schizophrenia loci by homozygosity mapping using DNA microarray analysis.
abstract: The recent development of high-resolution DNA microarrays, in which hundreds of thousands of single nucleotide polymorphisms (SNPs) are genotyped, enables the rapid identification of susceptibility genes for complex diseases. Clusters of these SNPs may show runs of homozygosity (ROHs) that can be analyzed for association with disease. An analysis of patients whose parents were first cousins enables the search for autozygous segments in their offspring. Here, using the Affymetrix® Genome-Wide Human SNP Array 5.0 to determine ROHs, we genotyped 9 individuals with schizophrenia (SCZ) whose parents were first cousins. We identified overlapping ROHs on chromosomes 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 17, 19, 20, and 21 in at least 3 individuals. Only the locus on chromosome 5 has been reported previously. The ROHs on chromosome 5q23.3-q31.1 include the candidate genes histidine triad nucleotide binding protein 1 (HINT1) and acyl-CoA synthetase long-chain family member 6 (ACSL6). Other overlapping ROHs may contain novel rare recessive variants that affect SCZ specifically in our samples, given the highly heterozygous nature of SCZ. Analysis of patients whose parents are first cousins may provide new insights for the genetic analysis of psychiatric diseases.
authors.affiliation: Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. naokuro@nagasaki-u.ac.jp
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kurotaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Tasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mishima
authors.forename: Shinji
authors.initials: S
authors.lastname: Ono
authors.forename: Akira
authors.initials: A
authors.lastname: Imamura
authors.forename: Taeko
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Koh-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D000328:Adult; D003066:Coenzyme A Ligases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C063306:HINT1 protein, human; D009419:Nerve Tissue Proteins; D003066:Coenzyme A Ligases; C475689:Acsl6 protein, mouse