28 research outputs found
Genotyping and annotation of Affymetrix SNP arrays
In this paper we develop a new method for genotyping Affymetrix single nucleotide polymorphism (SNP) array. The method is based on (i) using multiple arrays at the same time to determine the genotypes and (ii) a model that relates intensities of individual SNPs to each other. The latter point allows us to annotate SNPs that have poor performance, either because of poor experimental conditions or because for one of the alleles the probes do not behave in a doseâresponse manner. Generally, our method agrees well with a method developed by Affymetrix. When both methods make a call they agree in 99.25% (using standard settings) of the cases, using a sample of 113 Affymetrix 10k SNP arrays. In the majority of cases where the two methods disagree, our method makes a genotype call, whereas the method by Affymetrix makes a no call, i.e. the genotype of the SNP is not determined. By visualization it is indicated that our method is likely to be correct in majority of these cases. In addition, we demonstrate that our method produces more SNPs that are in concordance with HardyâWeinberg equilibrium than the method by Affymetrix. Finally, we have validated our method on HapMap data and shown that the performance of our method is comparable to other methods
Lâutilisation des rĂ©seaux sociaux (Snapchat, WhatsApp et Instagram) et le cyberbullying
100% des jeunes possĂšdent un tĂ©lĂ©phone portable, 99% ont un ordinateur et 97% ont accĂšs Ă Internet (Waller et al., 2016). Ces nouveaux moyens technologiques font partie de notre quotidien. Depuis lâapparition de ces rĂ©seaux, un nouveau mouvement est nĂ© : le cyberbullying. Ce harcĂšlement par Internet consiste Ă lâutilisation de technologies modernes de communication afin de nuire aux autres de maniĂšre dĂ©libĂ©rĂ©e et agressive. Quand les jeunes arrivent en classe, ils apportent avec eux lâentier de leur vĂ©cu quotidien, familial ou encore Ă©motionnel. Les problĂšmes liĂ©s Ă lâutilisation massive de ces rĂ©seaux font partie de notre quotidien dâenseignant. Malheureusement, les Ă©tudes faites jusquâau jour dâaujourdâhui portent en majeure partie sur les Ă©lĂšves entre 13 ans et plus. Mais quâen est-il des jeunes ĂągĂ©s entre 9 et 12 ans ? Notre travail de recherche porte donc sur lâutilisation des rĂ©seaux sociaux (Snapchat, Instagram et WhatsApp) et le cyberbullying. Deux outils diffĂ©rents ont Ă©tĂ© utilisĂ©s lors de cette recherche : des questionnaires afin dâavoir des rĂ©sultats quantitatifs et deux entretiens afin dâavoir un point de vue qualitatif. Nos rĂ©sultats montrent que WhatsApp est le rĂ©seau social le plus utilisĂ©, suivi dâInstagram en deuxiĂšme position et finalement de Snapchat. Les Ă©lĂšves considĂšrent le nombre de dangers et de conflits sur les rĂ©seaux comme trĂšs faibles. Ils avouent tout de mĂȘme donner plus dâinformations personnelles sur WhatsApp que sur les autres rĂ©seaux choisis dans lâĂ©tude. Concernant leur vision du contrĂŽle des parents, ils lâestiment trĂšs faible. Cependant, il sâagit uniquement de leur avis, il serait intĂ©ressant de savoir la rĂ©alitĂ© des faits en interrogeant les parents. Les deux sujets interrogĂ©s savent dĂ©finir le cyberbullying et connaissent les diffĂ©rents acteurs agissant au sein de cette forme de harcĂšlement. Ils sont Ă©galement conscients des diffĂ©rents risques, consĂ©quences ou sentiments que peut ressentir une cyber-victime mais nâabordent pas du tout ceux concernant le tĂ©moin ou le cyber-harceleur. En conclusion, notre recherche montre que les rĂ©seaux sociaux font partie intĂ©grante du quotidien dâun grand nombre dâĂ©lĂšves. Il est donc essentiel que les enseignants sâinterrogent sur les moyens de gĂ©rer les problĂšmes que ceux-ci peuvent amener en classe mais Ă©galement les moyens de les Ă©viter
The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population
<p>Abstract</p> <p>Background</p> <p>Mutations in the mismatch repair genes <it>hMLH1 </it>and <it>hMSH2 </it>predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense, silent and non-coding) in <it>hMLH1 </it>and <it>hMSH2</it>. The aim of the present study was to investigate the frequency of these variants in <it>hMLH1 </it>and <it>hMSH2 </it>in Danish patients with sporadic colorectal cancer and in the healthy background population. The purpose was to reveal if any of the common variants lead to increased susceptibility to colorectal cancer.</p> <p>Methods</p> <p>Associations between genetic variants in <it>hMLH1 </it>and <it>hMSH2 </it>and sporadic colorectal cancer were evaluated using a case-cohort design. The genotyping was performed on DNA isolated from blood from the 380 cases with sporadic colorectal cancer and a sub-cohort of 770 individuals. The DNA samples were analyzed using Single Base Extension (SBE) Tag-arrays. A Bonferroni corrected Fisher exact test was used to test for association between the genotypes of each variant and colorectal cancer. Linkage disequilibrium (LD) was investigated using HaploView (v3.31).</p> <p>Results</p> <p>Heterozygous and homozygous changes were detected in 13 of 35 analyzed variants. Two variants showed a borderline association with colorectal cancer, whereas the remaining variants demonstrated no association. Furthermore, the genomic regions covering <it>hMLH1 </it>and <it>hMSH2 </it>displayed high linkage disequilibrium in the Danish population. Twenty-two variants were neither detected in the cases with sporadic colorectal cancer nor in the sub-cohort. Some of these rare variants have been classified either as pathogenic mutations or as neutral variants in other populations and some are unclassified Danish variants.</p> <p>Conclusion</p> <p>None of the variants in <it>hMLH1 </it>and <it>hMSH2 </it>analyzed in the present study were highly associated with colorectal cancer in the Danish population. High linkage disequilibrium in the genomic regions covering <it>hMLH1 </it>and <it>hMSH2</it>, indicate that common genetic variants in the two genes in general are not involved in the development of sporadic colorectal cancer. Nevertheless, some of the rare unclassified variants in <it>hMLH1 </it>and <it>hMSH2 </it>might be involved in the development of colorectal cancer in the families where they were originally identified.</p
Deleterious misâsplicing of STK11 caused by a novel singleânucleotide substitution in the 3âČ polypyrimidine tract of intron five
Abstract Background Pathogenic variants in STK11, also designated as LKB1, cause PeutzâJeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation changes, polyposis, and a high risk of cancer. Methods A male meeting the clinical diagnostic criteria for PeutzâJeghers syndrome underwent nextâgeneration sequencing. To validate the predicted splicing impact of a detected STK11 variant, we performed RNAâSeq on mRNA extracted from patientâderived EpsteinâBarr virusâtransformed lymphocytes treated with cycloheximide to inhibit nonsenseâmediated decay ex vivo. Results Blood testing identified a novel singleânucleotide substitution, NM_000455.4:c.735â10C>A, at the end of the 3âČ polypyrimidine tract of intron five in STK11. RNAâSeq confirmed a predicted eight base pair insertion in the mRNA transcript. Following inhibition of nonsenseâmediated decay, the outâofâframe insertion was detected in 50% of all RNAâSeq reads. This confirmed a strong, deleterious splicing impact of the variant. Conclusion We characterized a novel likely pathogenic germline variant in intron five of STK11 associated with PeutzâJeghers syndrome. The study highlights RNAâSeq as a useful supplement in hereditary cancer predisposition testing