The genetic architecture of the AVSD risk in Down syndrome: results from chromosome 21 sequencing

Diplôme Master The genetic architecture of the AVSD risk in Down syndrome: results from chromosome 21 sequencing eng 2018 author Blanc Xavier 841629 director Antonarakis Stylianos 22813 director Sanchez-Mazas Alicia 22545 Down syndrome (DS) patients are often born with congenital heart defects (CHD), including atrioventricular septal defect (AVSD). The incidence of AVSD is 43% in DS-CHD patients (17% in the DS population) and very rare in the general population. Here we use chromosome 21-targeted deep sequencing (>120x) to perform a case-control association study in an AVSD population (102 cases, 145 controls) to identify SNPs, indels and CNVs associated with the AVSD in DS. SNPs and short indels are called through our in-house pipelines implementing BWA, GATK and Annovar. The association study is performed by Firth logistic regression following different genetic models and correcting for population stratification. Epistasis analysis is as well done using logistic interaction with interacting term. We also perform CNVs detection with the Nexus copy number software and statistical analysis with an in-house workflow. This study shows that common variants on chromosome 21 may contribute to the developmental phenotype of AVSD and provide insights into the understanding of the genetic mechanisms underlying the development of this heart defect. Down syndrome DS T21 Trisomy Congenital heart defect Congenital heart disease CHD Atrioventricular septal defect AVSD Sequencing Targeted resequencing Logistic regression SNP Indel CNV Epistasis Association study Dewey 570 Dewey 576.5 Master in Biology orientation Bioinformatics and data analysis in biology 30 Section de biologie 16 135 Département de médecine génétique et développement 21D false 3330f588-10a4-45b9-aabd-7b70467995d2 Master thesis Restricted Thesis_XB_final_22_01_18.pdf 4690677 application/pdf restrictedAccess Faculté des sciences / Section de biologie Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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The genetic architecture of the AVSD risk in Down syndrome: results from chromosome 21 sequencing				2018	157	21

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Blanc, Xavier