The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

Vega, Francisco; Isaac, Hadar; Collins, Andrew; Scafe, Charles; Halldórsson, Bjarni V.; Su, Xiaoping; Lippert, Ross A.; Wang, Yu; Laig-Webster, Marion; Koehler, Ryan T.; Ziegle, Janet; Wogan, Lewis T.; Stevens, Junko; Leinen, Kyle M.; Olson, Sheri J.; Guegler, Karl; You, Xiaoqing; Xu, Lily H.; Hemken, Heinz G.; Kalush, Francis; Itakura, Mitsuo; Zheng, Yi; O’Brien, Stephen J.; Clark, Andrew G.; Istrail, Sorin; Hunkapiller, Michael W.; Spier, Eugene G.; Gilbert, Dennis A.

doi:10.1101/gr.3241705

Cited by 110 publications

(63 citation statements)

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“…Blood specimens were collected from all study subjects. An additional set of 46 DNA samples was obtained from unrelated healthy Japanese volunteers (24 men and 22 women) at The University of Tokushima, and was used for optimization of the SNP genotyping assay and estimating allele frequencies, as previously described (29). Genomic DNA samples were extracted from peripheral blood leukocytes according to standard methods.…”

Section: Methodsmentioning

confidence: 99%

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Takata¹,

Hamada²,

Miyatake³

et al. 2007

Arthritis & Rheumatism

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Objective. Analyses of families with rheumatoid arthritis (RA) have suggested the presence of a putative susceptibility locus on chromosome 14q21-23. This large population-based genetic association study was undertaken to examine this region.Methods. A 2-stage case-control association study of 950 unrelated Japanese patients with RA and 950 healthy controls was performed using >400 genebased common single-nucleotide polymorphisms (SNPs).Results. Multiple SNPs in the PRKCH gene encoding the isozyme of protein kinase C (PKC) showed significant single-locus disease associations, the most significant being SNP c.427؉8134C>T (odds ratio 0.72, 95% confidence interval 0.62-0.83, P ‫؍‬ 5.9 ؋ 10 ؊5 ). Each RA-associated SNP was consistently mapped to 3 distinct regions of strong linkage disequilibrium (i.e., linkage disequilibrium or haplotype blocks) in the PRKCH gene locus, suggesting that multiple causal variants influence disease susceptibility. Significant SNPs included a novel common missense polymorphism of the PRKCH gene, V374I (rs2230500), which lies within the ATP-binding site that is highly conserved among PKC superfamily members. In circulating lymphocytes, PRKCH messenger RNA was expressed at higher levels in resting T cells (CD4؉ or CD8؉) than in B cells (CD19؉) or monocytes (CD14؉) and was significantly down-regulated through immune responses.Conclusion. Our results provide evidence of the involvement of PRKCH as a susceptibility gene for RA in the Japanese population. Dysregulation of PKC signal transduction pathway(s) may confer increased risk of RA through aberrant T cell-mediated autoimmune responses.

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Section: Methodsmentioning

confidence: 99%

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Takata¹,

Hamada²,

Miyatake³

et al. 2007

Arthritis & Rheumatism

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“…16,17 It is also possible that SNPs that are physically close to each Designing pharmacogenetic projects in industry CM Bromley et al other may be in weak LD, 18 for instance if SNPs are in recombination hotspots, LD would be reduced. The success of a SNP association study depends partially on how well the assayed SNPs 'cover', or 'tag' the putative causal variants.…”

Section: Selecting Genetic Polymorphisms and Other Variationmentioning

confidence: 99%

Designing pharmacogenetic projects in industry: practical design perspectives from the Industry Pharmacogenomics Working Group

Bromley¹,

Cohen

et al. 2008

Pharmacogenomics J

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Pharmacogenetic association studies have the potential to identify variations in DNA sequence which impact drug response. Identifying these DNA variants can help to explain interindividual variability in drug response; this is the first step in personalizing dosing and treatment regimes to a patient's needs. There are many intricacies in the design and analysis of pharmacogenetic association studies, including having adequate power, selecting proper endpoints, detecting and correcting the effects of population stratification, modeling genetic and nongenetic covariates accurately, and validating the results. At this point there are no formal guidelines on the design and analysis of pharmacogenetic studies. The Industry Pharmacogenomics Working Group has initiated discussions regarding potential guidelines for pharmacogenetic study design and analyses (http://i-pwg.org) and the results from these discussions are presented in this paper.

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“…Measures of LD, gene density, and haplotype blocks vary across the genome (Ke et al 2004;De la Vega et al 2005), and the HapMap ENCODE regions analyzed represent a range of these and other characteristics (The ENCODE Project Consortium 2004), suggesting that our results may apply, on average, across the genome. The strong correlations observed between Cebu Filipino samples and HapMap Asian panels are broadly consistent with other assessments of tagging transferability outside the HapMap ENCODE regions (Weale et al 2003;Nejentsev et al 2004;Ke et al 2005;Mueller et al 2005;Ramirez-Soriano et al 2005;Evans and Cardon 2005;Gonzalez-Neira et al 2006;Huang et al 2006;Mahasirimongkol et al 2006;Montpetit et al 2006;Ribas et al 2006;Willer et al 2006).…”

Section: Discussionmentioning

confidence: 97%

Comparison of ENCODE region SNPs between Cebu Filipino and Asian HapMap samples

Marvelle

Lange

et al. 2007

J Hum Genet

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Patterns of linkage disequilibrium (LD) act as the framework for designing efficient association studies; these patterns are being studied and catalogued by The International HapMap Project. The current study assessed the transferability of tag SNPs chosen from HapMap panels to a cohort of 80 individuals from metro Cebu, Philippines, who participated in the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The analyses focused on 627 single nucleotide polymorphisms (SNPs) in the central 40 kb within each of the 10 HapMap ENCODE regions. The similarity between the genetic variants in Cebu Filipino samples and HapMap panels was examined using allele frequency estimates, measures of pairwise linkage disequilibrium (LD), and haplotype frequency estimates. For these measures, strong correlations were observed between the Cebu Filipino samples and the Asian panels from HapMap, with the strongest correlations observed with the Han Chinese from Beijing (CHB) panel. Tag SNPs selected using the HapMap CHB panel were particularly effective at representing the genetic variation in Cebu Filipino samples. These results suggest that the HapMap data will be an effective resource for future studies in Cebu Filipino samples.

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The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

Cited by 110 publications

References 50 publications

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Designing pharmacogenetic projects in industry: practical design perspectives from the Industry Pharmacogenomics Working Group

Comparison of ENCODE region SNPs between Cebu Filipino and Asian HapMap samples

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