Dataset Information

Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in relation to schizophrenia.

ABSTRACT: The regulator of G-protein signaling 4 (RGS4, chromosome 1q23.3) plays a critical role in G-protein function. Four common single-nucleotide polymorphisms (SNPs) localized between the 5' upstream sequence and the first intron, as well as 2 haplotypes derived from these SNPs may confer liability to schizophrenia (SZ). However, the pattern of associations varies among samples. To help clarify the putative associations, we report the following analyses: (1) a comprehensive catalog of common polymorphisms, (2) linkage disequilibrium (LD) and association analyses using these SNPs, and (3) functional analysis based on dual-luciferase promoter assays. We identified 62 SNPs from a 20-kb genomic region spanning RGS4, of which 26 are common polymorphisms with a minor allele frequency (MAF) of >5%. LD analysis suggested 5 clusters of SNPs (r(2) > .8). Association analyses using the novel SNPs were consistent with the prior reports, but further localization was constrained by significant LD across the region. The 2 haplotypes reported to confer liability to SZ had significant promoter activity compared with promoterless constructs, suggesting a functional role for both haplotypes. Further analyses of promoter sequences are warranted to understand transcriptional regulation at RGS4. This information will be useful for further analysis of samples in which genetic association of RGS4 polymorphisms with SZ has been reported.

SUBMITTER: Chowdari KV

PROVIDER: S-EPMC2632380 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in relation to schizophrenia.

Chowdari Kodavali V KV Bamne Mikhil M Wood Joel J Talkowski Michael E ME Mirnics Karoly K Levitt Pat P Lewis David A DA Nimgaonkar Vishwajit L VL

Schizophrenia bulletin 20070521 1

The regulator of G-protein signaling 4 (RGS4, chromosome 1q23.3) plays a critical role in G-protein function. Four common single-nucleotide polymorphisms (SNPs) localized between the 5' upstream sequence and the first intron, as well as 2 haplotypes derived from these SNPs may confer liability to schizophrenia (SZ). However, the pattern of associations varies among samples. To help clarify the putative associations, we report the following analyses: (1) a comprehensive catalog of common polymorp ...[more]

PMID: 17515439

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Project description:BackgroundStructural variants (SV) are causative for some prominent phenotypic traits of livestock as different comb types in chickens or color patterns in pigs. Their effects on production traits are also increasingly studied. Nevertheless, accurately calling SV remains challenging. It is therefore of interest, whether close-by single nucleotide polymorphisms (SNPs) are in strong linkage disequilibrium (LD) with SVs and can serve as markers. Literature comes to different conclusions on whether SVs are in LD to SNPs on the same level as SNPs to other SNPs. The present study aimed to generate a precise SV callset from whole-genome short-read sequencing (WGS) data for three commercial chicken populations and to evaluate LD patterns between the called SVs and surrounding SNPs. It is thereby the first study that assessed LD between SVs and SNPs in chickens.ResultsThe final callset consisted of 12,294,329 bivariate SNPs, 4,301 deletions (DEL), 224 duplications (DUP), 218 inversions (INV) and 117 translocation breakpoints (BND). While average LD between DELs and SNPs was at the same level as between SNPs and SNPs, LD between other SVs and SNPs was strongly reduced (DUP: 40%, INV: 27%, BND: 19% of between-SNP LD). A main factor for the reduced LD was the presence of local minor allele frequency differences, which accounted for 50% of the difference between SNP - SNP and DUP - SNP LD. This was potentially accompanied by lower genotyping accuracies for DUP, INV and BND compared with SNPs and DELs. An evaluation of the presence of tag SNPs (SNP in highest LD to the variant of interest) further revealed DELs to be slightly less tagged by WGS SNPs than WGS SNPs by other SNPs. This difference, however, was no longer present when reducing the pool of potential tag SNPs to SNPs located on four different chicken genotyping arrays.ConclusionsThe results implied that genomic variance due to DELs in the chicken populations studied can be captured by different SNP marker sets as good as variance from WGS SNPs, whereas separate SV calling might be advisable for DUP, INV, and BND effects.

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Dataset Information

Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in relation to schizophrenia.

Publications

Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in relation to schizophrenia.

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