Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between <it>D15S118 </it>and <it>D15S117 </it>in a Japanese population using a region-wide case-control association test.</p> <p>Methods</p> <p>A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed.</p> <p>Results</p> <p>SNP2140 (rs2412747) (<it>C/T</it>) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (<it>UBR1</it>) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal <it>p </it>value (<it>p </it>= 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07–1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing.</p> <p>Conclusion</p> <p>The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.</p

Global similarity with local differences in linkage disequilibrium between the Dutch and HapMap–CEU populations

The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies only a few loci were evaluated. We compared pair-wise LD and LD block structure across autosomes between the Dutch population and the CEU-HapMap reference panel. The impact of sampling distribution on the estimation of LD blocks was studied by bootstrapping. A high Pearson correlation (genome-wide; 0.93) between pair-wise

Methylation level of cotton genotypes determined by MSAP.

<p>The average genome-wide methylation level measured by MSAP for <i>G. hirsutum</i> and <i>G. barbadense</i> was 49.7% and 51.9%, respectively. No significant differences in CG or CC methylation were found between genotypes. Significant differences found in CHG methylation is denoted by different letters.</p

PCA of the ten genotypes for each enzyme combinations plotted in two dimensions.

<p>The spatial distance on the graph represents the genetic/DNA methylation relationship between each genotype. Genetic and DNA methylation relationship between the genotypes is more distant between the genetic and DNA methylation state forming genetic, CG methylation, CHG methylation clusters. The CHG methylation and genetic component are closely related, whereas the CG methylation is more distant. The <i>G. barbadense</i> genotypes (CPX12 and Sipima 280) and Coker 315-11 are outliers that are distant from the three clusters, genetically and epigenetically.</p

Genetic and DNA Methylation Changes in Cotton (<i>Gossypium</i>) Genotypes and Tissues

<div><p>In plants, epigenetic regulation is important in normal development and in modulating some agronomic traits. The potential contribution of DNA methylation mediated gene regulation to phenotypic diversity and development in cotton was investigated between cotton genotypes and various tissues. DNA methylation diversity, genetic diversity, and changes in methylation context were investigated using methylation-sensitive amplified polymorphism (MSAP) assays including a methylation insensitive enzyme (<i>Bsi</i>SI), and the total DNA methylation level was measured by high-performance liquid chromatography (HPLC). DNA methylation diversity was greater than the genetic diversity in the selected cotton genotypes and significantly different levels of DNA methylation were identified between tissues, including fibre. The higher DNA methylation diversity (CHG methylation being more diverse than CG methylation) in cotton genotypes suggest epigenetic regulation may be important for cotton, and the change in DNA methylation between fibre and other tissues hints that some genes may be epigenetically regulated for fibre development. The novel approach using <i>Bsi</i>SI allowed direct comparison between genetic and epigenetic diversity, and also measured CC methylation level that cannot be detected by conventional MSAP.</p></div

Dendrogram of the ten genotypes constructed using the similarity coefficient.

<p><i>G. hirsutum</i> species are indicated by “<i>Gh</i>” and <i>G. barbadense</i> species are indicated by “<i>Gb</i>”. The separation of species and Coker 315-11 from other <i>G. hirsutum</i> genotypes is consistent in all dendrograms, but the relationships between G. hirsutum genotypes are different. Separation of genetic, CHG and CG methylation clusters in <i>G. hirsutum</i> genotypes (except Coker 315-11) show clear genetic/DNA methylation divergence in cultivated cotton.</p

Percentage of total methylation (%mdC) level of Coker 315-11 tissues determined by HPLC.

<p>Different letters above the bars denotes samples that have significantly different levels of methylation (p-value of <0.05). The error bars represent the standard error of the mean. Different tissues from 3-week-old plantlet and 6-months-old mature plant were used.</p