title: Genomic approaches to diagnose rare bone disorders.
abstract: Skeletal dysplasias are Mendelian disorders with a prevalence of approximatively 1 in every 5000 individuals and can usually be diagnosed based on clinical and radiological findings. However, given that some diseases can be caused by several different genes, and that some genes can cause a variety of different phenotypes, achieving a molecular diagnosis can be challenging. We review here different approaches, from single gene sequencing to genomic approaches using next-generation sequencing, to reach a molecular diagnosis for skeletal dysplasias. We will further describe the overall advantages and limitations of first, second and third-generation sequencing, including single gene sequencing, whole-exome and genome sequencing (WES and WGS), multiple gene panel sequencing and single molecule sequencing. We also provide a brief overview of potential future applications of emerging technologies.
authors.affiliation: CHU Sainte-Justine Research Center, Montreal, Canada; Division of Molecular and Cellular Biology, Department of Biology, University of Sherbrooke, Sherbrooke, Canada.
authors.forename: Félix
authors.initials: F
authors.lastname: Falardeau
authors.affiliation: CHU Sainte-Justine Research Center, Montreal, Canada.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Camurri
authors.affiliation: CHU Sainte-Justine Research Center, Montreal, Canada; Division of Medical Genetics, Department of Pediatrics, University of Montreal, Montreal, Canada. Electronic address: p.campeau@umontreal.ca.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Campeau
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035583:Rare Diseases / Q000235:genetics*
chemical_list: D006025:Glycosaminoglycans
keywords: Molecular and clinical diagnosis; Next-generation sequencing; Skeletal dysplasias