Entre Sélection et GénomiqueSéminaire Selgen 2014

Paris, 17-18 décembre 2014

BovCNV: The Bovine CNV ProjectRabia LETAIEF1, Mekki BOUSSAHA1, Emmanuelle REBOURS1, Didier BOICHARD1, Romain PHILIPPE2, Lionel FORESTIER2, Véronique BLANQUET2, Abdou MAFTAH2, Alain PINTON3, Dominique ROCHA1

1 Unité Génétique Animale et Biologie Intégrative, Jouy-en-Josas2 Unité Génétique Moléculaire Animale, Limoges3 Unité Génétique Physiologie et Systèmes d’Elevage, Toulouse

Scientific context Copy Number Variants (CNVs) are a novel type of polymorphism involving large regions, often corresponding to duplications or deletions of chromosomal fragments. These CNVs have been discovered recently and are under strong investigations because of their potential functional effect, therefore possibly altering phenotypes of interest.CNVs have been discovered first in Human in 2003-2004 and CNVs have also been analysed in many species, including in cattle, however only few bovine breeds have been studied, so far.The aim of the PhD project is to identify and characterize CNVs in a large number of cattle breeds. After the discovery phase based on the use of whole-genome sequences, a large number of CNVs will be validated using different experimental approaches. The putative effects of some of these polymorphisms on agronomical-related traits will be then investigated, after imputing CNV genotypes on animals with phenotypes.The BovCNV project will involve three INRA laboratories (located in Jouy, Limoges and Toulouse) but also at least two foreign research teams (from Canada and Denmark). With the help of the different collaborators of the “Bovine CNV project”, whole-genome sequencing data from different animals representing more than a dozen of different bovine breeds, including at least seven French breeds will be analyzed.

Work plan The project will be divided into three main phases. Phase 1: Identification of putative CNVsIn the first task we will discover putative CNVs by exploiting first whole-genome sequences (WGS). We will use more than 400 whole-genome sequences, from animal covering several beef and dairy breeds, generated by ourselves and our international collaborators. The BAM files will be analyzed with CNVnator and CNVSeq to identify putative CNVs. We will also exploit SNP genotyping data obtained using Illumina bovine HD BeadChips and generated during the French GEMBAL project (>5,000 animals from 18 different French bovine breeds). The SNP genotyping data will be analyzed with GenomeStudio (Illumina) and PennCNV softwares in order to identify CNVs. The list of putative CNVs obtained from WGS data will be compared to CNVs identified from the genotyping data. In addition, these CNVs will be annotated in order to identify those harboring genes and therefore that might have a functional impact. Phase 2: Validation of selected CNVsIn the second task, a large number of CNVs will be validated using different experimental approaches. CNVRs found frequently (in many different breeds) and/or with potentially a functional impact (i.e. harboring genes) will be further investigated. We will validate the selected CNVs using CGH microarrays, a SNP genotyping-based approach and quantitative PCR. Phase 3: Analysis of the effects of some CNVsIn the third task, the putative effects of some of these polymorphisms on agronomical-related traits will be investigated. CNVs will be genotyped in several thousands of animals (mostly from the three main French dairy breeds: Holstein, Montbéliarde and Normande) with phenotypic records. Association studies will then be performed in order to identify CNVs impacting phenotypes of interest.

Expected impact of the project

The aim of the project is to develop a catalogue of CNVs found in cattle. Thanks to the collaborations of three INRA laboratories and of international research teams, we will survey a large number of bovine breeds. This survey is the preliminary step, before being able to perform GWAS and genomic selection, combining SNP and CNV genotypes. The results of the project could therefore have an impact on genomic selection and the methods used and developed during this project could be used to study CNVs in other species.