Linkage Disequilibrium Grouping of Single Nucleotide Polymorphisms (SNPs) Reflecting Haplotype Phylogeny for Efficient Selection of Tag SNPs

Takeuchi, Fumihiko; Yanai, Kazuyuki; Morii, Toshiyuki; Ishinaga, Yuji; Taniguchi-Yanai, Keiko; Nagano, S.; Kato, Norihiro

doi:10.1534/genetics.104.038232

Cited by 28 publications

(22 citation statements)

References 13 publications

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“…Sequences for the primer and probe sets were obtained from the JMDBase (Japan Metabolic Disease Data Base, ENPP1_6-AC, http://www.jmdbase.jp/gene_snp.asp? geneid=23101&chrnum=3), a database for metabolic disorder-related SNPs (Takeuchi et al 2005), and purchased from Applied Biosystems. All reactions were performed according to the manufacturer's protocol using TaqMan Universal PCR Master Mix, No AmpErase UNG (Applied Biosystems), with a 900 nM primer/200 nM probe final concentration and 5.0 ng genomic DNA, in a total reaction volume of 4 ll.…”

Section: Enpp1 K121q Genotypingmentioning

confidence: 99%

No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population

et al. 2006

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Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we undertook an extensive case-control association study using a total of 911 unrelated Japanese T2D patients and 876 control subjects. No significant difference was observed in either genotype distribution (P=0.95) or allele frequency (P=0.83) between T2D and control groups. Notably, the frequency of the ancestral Q121 allele, which is also present in other primates, was quite high in AfricanAmericans, and showed a marked ethnic variation (77.3% in African-Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han Chinese). Consequently, the pairwise F ST value (a classic measure of genetic distance between pairs of population) showed highly significant differentiations between African-American and non-African-American populations (F ST >0.3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D.

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Section: Enpp1 K121q Genotypingmentioning

confidence: 99%

No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population

et al. 2006

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“…15%) SNPs. Given the low level of LD found in pine, which resulted in short LD blocks, other approaches to identify htSNPs, such as the identification of LD subgroups within LD blocks (see Takeuchi et al 2005 for details), did not perform well and are not shown.…”

Section: Methodsmentioning

confidence: 99%

DNA Sequence Variation and Selection of Tag Single-Nucleotide Polymorphisms at Candidate Genes for Drought-Stress Response in Pinus taeda L.

et al. 2006

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Genetic association studies are rapidly becoming the experimental approach of choice to dissect complex traits, including tolerance to drought stress, which is the most common cause of mortality and yield losses in forest trees. Optimization of association mapping requires knowledge of the patterns of nucleotide diversity and linkage disequilibrium and the selection of suitable polymorphisms for genotyping. Moreover, standard neutrality tests applied to DNA sequence variation data can be used to select candidate genes or amino acid sites that are putatively under selection for association mapping. In this article, we study the pattern of polymorphism of 18 candidate genes for drought-stress response in Pinus taeda L., an important tree crop. Data analyses based on a set of 21 putatively neutral nuclear microsatellites did not show population genetic structure or genomewide departures from neutrality. Candidate genes had moderate average nucleotide diversity at silent sites (p sil ¼ 0.00853), varying 100-fold among single genes. The level of within-gene LD was low, with an average pairwise r 2 of 0.30, decaying rapidly from 0.50 to 0.20 at 800 bp. No apparent LD among genes was found. A selective sweep may have occurred at the early-response-to-drought-3 (erd3) gene, although population expansion can also explain our results and evidence for selection was not conclusive. One other gene, ccoaomt-1, a methylating enzyme involved in lignification, showed dimorphism (i.e., two highly divergent haplotype lineages at equal frequency), which is commonly associated with the long-term action of balancing selection. Finally, a set of haplotype-tagging SNPs (htSNPs) was selected. Using htSNPs, a reduction of genotyping effort of 30-40%, while sampling most common allelic variants, can be gained in our ongoing association studies for drought tolerance in pine.

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“…We selected 92% of the detected SNPs as tag SNPs (n = 676) by (1) grouping SNPs with mutual r 2 C 0.6 for haplotype construction, (2) inferring haplotypes in each group, and (3) then removing redundant SNPs that are in complete LD with reference to haplotypes showing a frequency of at least 5% (Takeuchi et al 2005). Genotyping was performed either with TaqMan 1 SNP Genotyping Assays in ABI 7900HT (Applied Biosystems, Foster City, CA, USA) or with the MassARRAY 1 Compact system (Sequenom-Bruker, San Diego, CA, USA) according to the manufacturer's protocols.…”

Section: Methodsmentioning

confidence: 99%

HapMap coverage for SNPs in the Japanese population

2007

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The coverage of human genomic variations is known to substantially affect the success of genome-wide association studies. We therefore assessed the SNP coverage in the HapMap database for a total of 1,304 subjects from the Japanese population by combining resequencing and high-density genotyping approaches. First, we resequenced 48 Japanese subjects in 86 genes (572 kb in total), and we then genotyped the subset of tag SNPs and also imputed genotypes for all of the detected SNPs in an additional panel of 1,256 subjects. Subsequently, we genotyped 555,352 tag SNPs selected from the HapMap in 72 Japanese subjects (from the panel of 1,256 subjects) and further imputed genotypes for all SNPs currently included in the HapMap. Of 738 common genic SNPs (1.3 per kb) that we detected by resequencing, 58% had already been genotyped in the HapMap, and 31% were not genotyped but had a proxy SNP in the HapMap with a linkage disequilibrium coefficient r 2 C 0.8, whereas 11% were not represented in the current HapMap database. Thus, the HapMap coverage appears to be high although not thorough for SNPs in the Japanese population as compared to its coverage reported in Caucasians, and this needs to be considered when we interpret association results.

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Linkage Disequilibrium Grouping of Single Nucleotide Polymorphisms (SNPs) Reflecting Haplotype Phylogeny for Efficient Selection of Tag SNPs

Cited by 28 publications

References 13 publications

No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population

No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population

DNA Sequence Variation and Selection of Tag Single-Nucleotide Polymorphisms at Candidate Genes for Drought-Stress Response in Pinus taeda L.

HapMap coverage for SNPs in the Japanese population

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