Fondation Jean Dausset CEPH

Paris, France

Fondation Jean Dausset CEPH

Paris, France
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Huang J.,Tongji University | Renault V.,Fondation Jean Dausset CEPH | Sengenes J.,French Atomic Energy Commission | Touleimat N.,Fondation Jean Dausset CEPH | And 5 more authors.
Bioinformatics | Year: 2012

Motivation: We present a pipeline for the pre-processing, quality assessment, read distribution and methylation estimation for methylated DNA immunoprecipitation (MeDIP)-sequence datasets. This is the first MeDIP-seq-specific analytic pipeline that starts at the output of the sequencers. This pipeline will reduce the data analysis load on staff and allows the easy and straightforward analysis of sequencing data for DNA methylation. The pipeline integrates customized scripting and several existing tools, which can deal with both paired and single end data. © The Author 2011. Published by Oxford University Press. All rights reserved.

Genin E.,University Paris Diderot | Genin E.,French Institute of Health and Medical Research | Sahbatou M.,Fondation Jean Dausset CEPH | Gazal S.,University Paris Diderot | And 4 more authors.
Human Heredity | Year: 2012

To detect fully penetrant rare recessive variants that could constitute Mendelian subentities of complex diseases, we propose a novel strategy, the HBD-GWAS strategy, which can be applied to genome-wide association study (GWAS) data. This strategy first involves the identification of inbred individuals among cases using the genome-wide SNP data and then focuses on these inbred affected individuals and searches for genomic regions of shared homozygosity by descent that could harbor rare recessive disease-causing variants. In this second step, analogous to homozygosity mapping, a heterogeneity lod-score, HFLOD, is computed to quantify the evidence of linkage provided by the data. In this paper, we evaluate this strategy theoretically under different scenarios and compare its performances with those of linkage analysis using affected sib-pair (ASP) data. If cases affected by these Mendelian subentities are not enriched in the sample of cases, the HBD-GWAS strategy has almost no power to detect them, unless they explain an important part of the disease prevalence. The HBD-GWAS strategy outperforms the ASP linkage strategy only in a very limited number of situations where there exists a strong allelic heterogeneity. When several rare recessive variants within the same gene are involved, the ASP design indeed often fails to detect the gene, whereas, by focusing on inbred individuals using the HBD-GWAS strategy, the gene might be detected provided very large samples of cases are available. Copyright © 2013 S. Karger AG, Basel.

Jalkh N.,Saint - Joseph University | Jalkh N.,University of Versailles | Sahbatou M.,Fondation Jean Dausset CEPH | Chouery E.,Saint - Joseph University | And 4 more authors.
European Journal of Human Genetics | Year: 2015

Consanguineous marriages have been widely practiced in several global communities with varying rates depending on religion, culture, and geography. In consanguineous marriages, parents pass to their children autozygous segments known as homozygous by descent segments. In this study, single-nucleotide polymorphisms were analyzed in 165 unrelated Lebanese people from Greek Orthodox, Maronite, Shiite and Sunni communities. Runs of homozygosity, total inbreeding levels, remote consanguinity, and population admixture and structure were estimated. The inbreeding coefficient value was estimated to be 1.61% in offspring of unrelated parents over three generations and 8.33% in offspring of first cousins. From these values, remote consanguinity values, resulting from genetic drift or recurrent consanguineous unions, were estimated in offspring of unrelated and first-cousin parents to be 0.61 and 1.2%, respectively. This remote consanguinity value suggests that for any unrelated marriages in Lebanon, the mates could be related as third cousins or as second cousins once removed. Under the assumption that 25% of marriages occur between first cousins, the mean inbreeding value of 2.3% may explain the increased incidence of recessive disease in offspring. Our analysis reveals a common ancestral population in the four Lebanese communities we studied. © 2015 Macmillan Publishers Limited. All rights reserved.

Huang J.,Tongji University | Huang J.,Harvard University | Chen J.,Harvard University | Lathrop M.,Fondation Jean Dausset CEPH | Liang L.,Harvard University
Bioinformatics | Year: 2013

RNA sequencing data are becoming a major method of choice to study transcriptomes, including the mapping of gene expression quantitative trait loci (eQTLs). RNA sample contamination or swapping is a serious problem for downstream analysis and may result in false discovery and lose power to detect the true biological relationships. When genetic data are available, for example, in eQTL studies or samples have been previously genotyped or DNA sequenced, it is possible to combine genetic data and RNA-seq data to detect sample contamination and resolve sample swapping problems. In this article, we introduce a tool (IDCheck) that allows easy assessment of concordance between genotype (from SNP arrays or DNA sequencing) and gene expression (RNA-seq) samples. IDCheck compares the identity of RNA-seq reads and SNP genotypes using a likelihood-based method. Based on maximum likelihood estimates of relevant parameters, we can detect sample contamination and identify correct sample pairs when swapping occurs. Our tool provides an efficient and convenient way to evaluate and resolve these problems. © The Author 2013. Published by Oxford University Press. All rights reserved.

Gazal S.,French Institute of Health and Medical Research | Gazal S.,University Paris - Sud | Sahbatou M.,Fondation Jean Dausset CEPH | Babron M.-C.,French Institute of Health and Medical Research | And 5 more authors.
Bioinformatics | Year: 2014

Summary: FSuite is a user-friendly pipeline developed for exploiting inbreeding information derived from human genomic data. It can make use of single nucleotide polymorphism chip or exome data. Compared with other software, the advantage of FSuite is that it provides a complete suite of scripts to describe and use the inbreeding information. It includes a module to detect inbred individuals and estimate their inbreeding coefficient, a module to describe the proportion of different mating types in the population and the individual probability to be offspring of different mating types that can be useful for population genetic studies. It also allows the identification of shared regions of homozygosity between affected individuals (homozygosity mapping) that can be used to identify rare recessive mutations involved in monogenic or multifactorial diseases. © The Author 2014.

Fondation Jean Dausset Ceph | Date: 2012-02-27

The invention concerns genes involved in inflammatory and/or immune diseases and some cancers, in particular intestinal cryptogenic inflammatory diseases, and proteins coded by said genes. The invention also concerns methods for diagnosing inflammatory diseases.

PubMed | French Institute of Health and Medical Research and Fondation Jean Dausset CEPH
Type: | Journal: Scientific reports | Year: 2015

The 1000 Genomes Project provides a unique source of whole genome sequencing data for studies of human population genetics and human diseases. The last release of this project includes more than 2,500 sequenced individuals from 26 populations. Although relationships among individuals have been investigated in some of the populations, inbreeding has never been studied. In this article, we estimated the genomic inbreeding coefficient of each individual and found an unexpected high level of inbreeding in 1000 Genomes data: nearly a quarter of the individuals were inbred and around 4% of them had inbreeding coefficients similar or greater than the ones expected for first-cousin offspring. Inbred individuals were found in each of the 26 populations, with some populations showing proportions of inbred individuals above 50%. We also detected 227 previously unreported pairs of close relatives (up to and including first-cousins). Thus, we propose subsets of unrelated and outbred individuals, for use by the scientific community. In addition, because admixed populations are present in the 1000 Genomes Project, we performed simulations to study the robustness of inbreeding coefficient estimates in the presence of admixture. We found that our multi-point approach (FSuite) was quite robust to admixture, unlike single-point methods (PLINK).

PubMed | University of Bonn, Fondation Jean Dausset CEPH, Laboratoire Of Neuropathologie R Escourolle, Baylor College of Medicine and 4 more.
Type: | Journal: Scientific reports | Year: 2015

Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P=1.1510(-17)) for all forms of glioma - 26% (95% CI: 17-35%, P=1.0510(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P=1.2610(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (~6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.

PubMed | Bendat Family Comprehensive Cancer Center, Fondation Jean Dausset CEPH, University of Western Australia, National University of Singapore and 3 more.
Type: Journal Article | Journal: Journal of medical genetics | Year: 2016

Every colorectal cancer (CRC) patient should be tested for microsatellite instability (MSI, a marker for defective DNA mismatch repair) as a first screen for Lynch syndrome (LS). In this study, we investigated whether it may be possible to improve the detection of MSI in CRC. We examined whether the HT17 DNA repeat (critical for correct splicing of the chaperone HSP110) might constitute a superior marker for diagnosis of the MSI phenotype in patients with CRC compared with the standard panel of markers (pentaplex).The HT17 polymorphism was analysed in germline DNA from 1037 multi-ethnic individuals. We assessed its sensitivity and specificity for detecting MSI in a multicentre, population-based cohort of 685 patients with CRC and an additional series of 70 patients with CRC considered to be at-risk of LS. All cases were screened earlier for MSI using pentaplex markers. Cases showing discordant HT17/pentaplex results were further examined for the expression of mismatch repair proteins.HT17 status was analysed independently and blinded to previous results from pentaplex genotyping. HT17 showed no germline allelic variation outside a very narrow range. Compared with the pentaplex panel, HT17 showed better sensitivity (0.984 (95% CI 0.968 to 0.995) vs 0.951 (95% CI 0.925 to 0.972)) and similar specificity (0.997 (95% CI 0.989 to 1.000) for both) for the detection of MSI. Furthermore, HT17 alone correctly classified samples judged to be uncertain with the pentaplex panel and showed excellent ability to detect MSI in patients with LS.HT17 simplifies and improves the current standard molecular methods for detecting MSI in CRC.

PubMed | Lady Davis Institute for Medical Research, Georges Francois Leclerc Cancer Center, University of Lyon, University of Paris Pantheon Sorbonne and 15 more.
Type: Journal Article | Journal: The European respiratory journal | Year: 2015

Lung cancer in never-smokers (LCINS) (fewer than 100 cigarettes in lifetime) is considered as a distinct entity and harbours an original molecular profile. However, the epidemiological and molecular features of LCINS in Europe remain poorly understood. All consecutive newly diagnosed LCINS patients were included in this prospective observational study by 75 participating centres during a 14-month period. Each patient completed a detailed questionnaire about risk factor exposure. Biomarker and pathological analyses were also collected. We report the main descriptive overall results with a focus on sex differences. 384 patients were included: 65 men and 319 women. 66% had been exposed to passive smoking (significantly higher among women). Definite exposure to main occupational carcinogens was significantly higher in men (35% versus 8% in women). A targetable molecular alteration was found in 73% of patients (without any significant sex difference): EGFR in 51%, ALK in 8%, KRAS in 6%, HER2 in 3%, BRAF in 3%, PI3KCA in less than 1%, and multiple in 2%. We present the largest and most comprehensive LCINS analysis in a European population. Physicians should track occupational exposure in men (35%), and a somatic molecular alteration in both sexes (73%).

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