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Identification of novel schizophrenia loci by homozygosity mapping using DNA microarray analysis.

Kurotaki N, Tasaki S, Mishima H, Ono S, Imamura A, Kikuchi T, Nishida N, Tokunaga K, Yoshiura K, Ozawa H - PLoS ONE (2011)

Bottom Line: Only the locus on chromosome 5 has been reported previously.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. naokuro@nagasaki-u.ac.jp

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.

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Related in: MedlinePlus

Sum of run of homozygosity (ROH) lengths and number of overlapping patients, excluding patient siblings.Y-axis indicates the sum of ROH lengths shared by a given number of patients. The zero column indicates the sum of ROHs not shared by any of the samples.
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pone-0020589-g004: Sum of run of homozygosity (ROH) lengths and number of overlapping patients, excluding patient siblings.Y-axis indicates the sum of ROH lengths shared by a given number of patients. The zero column indicates the sum of ROHs not shared by any of the samples.

Mentions: The sum lengths of the overlapping regions among 0–7 independent family patients are shown in Figure 4, and the calculated percentage sum length among a given number of patients and more in the autosomal genome were as follows: 100%, 51.7%, 13.6%, 6.0%, 1.9%, 1.3%, and 0.6%. Considering the statistics, we adopted a minimum of 3 patients for identifying candidate loci. Figure 5 shows a schema of the overlapping ROHs within autosomes and their positions are summarized in Table S1.


Identification of novel schizophrenia loci by homozygosity mapping using DNA microarray analysis.

Kurotaki N, Tasaki S, Mishima H, Ono S, Imamura A, Kikuchi T, Nishida N, Tokunaga K, Yoshiura K, Ozawa H - PLoS ONE (2011)

Sum of run of homozygosity (ROH) lengths and number of overlapping patients, excluding patient siblings.Y-axis indicates the sum of ROH lengths shared by a given number of patients. The zero column indicates the sum of ROHs not shared by any of the samples.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105082&req=5

pone-0020589-g004: Sum of run of homozygosity (ROH) lengths and number of overlapping patients, excluding patient siblings.Y-axis indicates the sum of ROH lengths shared by a given number of patients. The zero column indicates the sum of ROHs not shared by any of the samples.
Mentions: The sum lengths of the overlapping regions among 0–7 independent family patients are shown in Figure 4, and the calculated percentage sum length among a given number of patients and more in the autosomal genome were as follows: 100%, 51.7%, 13.6%, 6.0%, 1.9%, 1.3%, and 0.6%. Considering the statistics, we adopted a minimum of 3 patients for identifying candidate loci. Figure 5 shows a schema of the overlapping ROHs within autosomes and their positions are summarized in Table S1.

Bottom Line: Only the locus on chromosome 5 has been reported previously.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. naokuro@nagasaki-u.ac.jp

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.

Show MeSH
Related in: MedlinePlus