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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

Size distribution of autosomal runs of homozygosity (ROHs).In the size distribution plot of non-consanguineous Japanese (non-CJ; A and B) and schizophrenia (SCZ; C and D) samples, the x-axis indicates the ROH size (log10 scale). A and C, individual average frequency of the ROHs as histograms. B and D, estimated probability density corresponding to each histogram. Black areas shows 1/16 (6.25%) of autosomes, which is equivalent to the expected sum of autozygous regions in the offspring of a first-cousin marriage. E, enlarged overlap of B (gray) and D (hatched). F, SCZ/non-CJ odds ratio plot. X-axis indicates the size of the ROHs (log10 scale). Y-axis (log10 scale) indicates the ratio of areas exceeding the given ROH size threshold in the estimated probability distributions of the SCZ and non-CJ datasets.
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pone-0020589-g003: Size distribution of autosomal runs of homozygosity (ROHs).In the size distribution plot of non-consanguineous Japanese (non-CJ; A and B) and schizophrenia (SCZ; C and D) samples, the x-axis indicates the ROH size (log10 scale). A and C, individual average frequency of the ROHs as histograms. B and D, estimated probability density corresponding to each histogram. Black areas shows 1/16 (6.25%) of autosomes, which is equivalent to the expected sum of autozygous regions in the offspring of a first-cousin marriage. E, enlarged overlap of B (gray) and D (hatched). F, SCZ/non-CJ odds ratio plot. X-axis indicates the size of the ROHs (log10 scale). Y-axis (log10 scale) indicates the ratio of areas exceeding the given ROH size threshold in the estimated probability distributions of the SCZ and non-CJ datasets.

Mentions: Detected ROHs were statistically analyzed and visualized (Figures 2 and 3; Tables 1 and 2) by using in-house scripts written in the R language [10]. The optimization of histogram bandwidths and the estimation of the probability density distributions were performed using the “KernSmooth” package of R [11].


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)

Size distribution of autosomal runs of homozygosity (ROHs).In the size distribution plot of non-consanguineous Japanese (non-CJ; A and B) and schizophrenia (SCZ; C and D) samples, the x-axis indicates the ROH size (log10 scale). A and C, individual average frequency of the ROHs as histograms. B and D, estimated probability density corresponding to each histogram. Black areas shows 1/16 (6.25%) of autosomes, which is equivalent to the expected sum of autozygous regions in the offspring of a first-cousin marriage. E, enlarged overlap of B (gray) and D (hatched). F, SCZ/non-CJ odds ratio plot. X-axis indicates the size of the ROHs (log10 scale). Y-axis (log10 scale) indicates the ratio of areas exceeding the given ROH size threshold in the estimated probability distributions of the SCZ and non-CJ datasets.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020589-g003: Size distribution of autosomal runs of homozygosity (ROHs).In the size distribution plot of non-consanguineous Japanese (non-CJ; A and B) and schizophrenia (SCZ; C and D) samples, the x-axis indicates the ROH size (log10 scale). A and C, individual average frequency of the ROHs as histograms. B and D, estimated probability density corresponding to each histogram. Black areas shows 1/16 (6.25%) of autosomes, which is equivalent to the expected sum of autozygous regions in the offspring of a first-cousin marriage. E, enlarged overlap of B (gray) and D (hatched). F, SCZ/non-CJ odds ratio plot. X-axis indicates the size of the ROHs (log10 scale). Y-axis (log10 scale) indicates the ratio of areas exceeding the given ROH size threshold in the estimated probability distributions of the SCZ and non-CJ datasets.
Mentions: Detected ROHs were statistically analyzed and visualized (Figures 2 and 3; Tables 1 and 2) by using in-house scripts written in the R language [10]. The optimization of histogram bandwidths and the estimation of the probability density distributions were performed using the “KernSmooth” package of R [11].

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