Séquençage de l'exome humain par NGS

Abstract

Whole exome sequencing (WES) is a targeted approach to genomic sequencing that involves specifically analyzing the coding regions of the genome, called exons. Although these regions represent only approximately 1 to 2% of the total genome, they account for nearly 85% of the mutations responsible for known genetic diseases. Thanks to the emergence of highthroughput sequencing (NGS – Next-Generation Sequencing) technologies, exome sequencing has become a key tool in biomedical research and genetic diagnosis. This thesis presents the various technical and bioinformatics steps of human exome sequencing, from DNA extraction to variant interpretation. It describes the preparation of DNA libraries, the enrichment of exonic regions, high-throughput sequencing (particularly via the MGI platform), as well as data processing (FASTQ files, alignment, variant calling, annotation, and interpretation of VCF files). The medical applications of WES are numerous, particularly in the diagnosis of rare diseases, neurological disorders, and certain oncological pathologies. However, this approach also has limitations, such as the inability to detect certain structural or regulatory mutations not covered by the exome. Thus, human exome sequencing using NGS is an efficient, rapid, and relatively economical method, offering great potential for personalized medicine and understanding the genetic mechanisms of human diseases.