Tag SNP Selection Based on Multivariate Linear Regression

Abstract. The search for the association between complex diseases and single nucleotide polymorphisms (SNPs) or haplotypes has been recently received great attention. For these studies, it is essential to use a small subset of informative SNPs (tag SNPs) accurately representing the rest of the SNPs. Tagging can achieve budget savings by genotyping only a limited number of SNPs and computationally inferring all other SNPs and compaction of extremely long SNP sequences (obtained, e.g., from Affimetrix Map Array) for further fine genotype analysis. Tagging should first choose tags from the SNPs under consideration and then knowing the values of chosen tag SNPs predict (or statistically cover) the non-tag SNPs. In this paper we propose a new SNP prediction method based on rounding of multivariate linear regression (MLR) analysis in sigmarestricted coding. When predicting a non-tag SNP, the MLR method accumulates information about all tag SNPs resulting in significantly higher prediction accuracy with the same number of tags than for the previously known tagging methods. We also show that the tag selection strongly depends on how the chosen tags will be used – advantage of one tag set over another can only be considered with respect to a certain prediction method. Two simple universal tag selection methods have been applied: a (faster) stepwise and a (slower) local-minimization tag selection algorithms. An extensive experimental study on various datasets including 6 regions from HapMap shows that the MLR prediction combined with stepwise tag selection uses significantly fewer tags (e.g., up to two times less tags to reach 90 % prediction accuracy) than the state-ofart methods of Halperin et al. [9] for genotypes and Halldorsson et al. [8] for haplotypes, respectively. Our stepwise tagging matches the quality of while being faster than STAMPA [9]. The code is publicly available a

Identifying Blocks and Sub-Populations in Noisy SNP Data

We study several problems arising in haplotype block partitioning. Ou

Malaysian primary school teachers’ use of and cognitions about digital technology for English as a second language literacy instruction: a case-based investigation

There have been few descriptive and in-depth studies of the use of digital technology (DT) in literacy instruction among teachers of English as a second/foreign language, especially in relatively low-resource contexts, and there has been limited research which investigates teachers’ cognitions about this use in detail. Understanding the teaching context and teacher cognition are important for improving the quality of teaching and learning in countries like Malaysia, for example via teacher education initiatives. The prime objectives of this study are: 1) to explore how Malaysian teachers use DT for English literacy instruction in the classroom; 2) to examine the nature of Malaysian teachers’ cognitions about (the use of) DT in ESL literacy instruction; 3) to investigate the sources of teachers’ cognitions; and 4) to examine how cognitions are related to actual use. The study utilises an exploratory case study approach, concentrating on three teachers in a rural context in Malaysia. The teachers were observed and interviewed, and the findings were triangulated in a structured analysis process. The results show that although these teachers believe in the capabilities of DT in improving teaching, they have concerns regarding the implementation of the use of technology. In addition, the teachers also face various challenges (mostly in extrinsic forms) that sometimes create obstacles for them to use DT in their teaching. However, intrinsic factors are seen to have a positive influence on their efforts to continue using DT in the classroom. The involved teachers try to balance their perceptions on the use of DT in the classroom, taking into account the positive and negative factors that will arise. These factors are not only dependent on intrinsic factors involving cognition and their experience using DT, but also external contextual and social factors such as student discipline, technical problems, school culture, availability of and access to DT, and so on. Given the importance of DT in the context of education in developing countries such as Malaysia, as well as the importance of understanding teacher cognition related to this aspect, this study has significant implications for researchers, teacher education, curriculum developers, teachers, students and more. This study proposes a modification of Borg’s (2003) model of teacher cognitions, highlighting the importance of considering contextual factors that influence all aspects of teacher cognition (i.e. early formal and informal education/experiences, teacher training and professional development and classroom practice). The model also shows that contextual factors are influential over different phases of a teacher’s life. Overall, this study also makes a contribution to research in its methodology in that it provides an in-depth qualitative study. The findings indicate that teaching experience builds knowledge of teaching methods and forms teachers’ teaching practices

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

Contains fulltext : 88175.pdf (publisher's version ) (Open Access)We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping

Identification of sequence variants influencing immunoglobulin levels

Proteomic

A Genome-Wide Association Study Identifies an Osteoarthritis Susceptibility Locus on Chromosome 7q22

Objective. To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. Methods. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and similar to 39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 x 10(-7) considered genome-wide significant. Results. The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09-1.19) of knee and/or hand OA (P = 8 x 10(-8)) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03-1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 x 10(-12)). Immunohistochemistry experiments revealed that G protein coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22-positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. Conclusion. Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein-coupled receptor, this is potentially an interesting therapeutic target.Pathophysiology and treatment of rheumatic disease