title: Point mutations as a source of de novo genetic disease.
abstract: Family-based next generation sequencing (NGS) has recently pointed to an important role for de novo germline point mutations in both rare and common genetic disorders associated with reduced fitness. In this review we highlight the impact of the mutational target size on the frequency of diseases caused by these de novo point mutations. In addition, we will discuss the human per-generation mutation rate, its relation to advanced paternal age and how these factors affect the frequency of genetic disease caused by de novo events.
authors: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: Joep
authors: J
authors: de Ligt
authors: Joris A
authors: JA
authors: Veltman
authors: Lisenka E L M
authors: LE
authors: Vissers
mesh_terms: D030342:Genetic Diseases, Inborn / Q000209:etiology / Q000473:pathology*; D015894:Genome, Human; D018095:Germ-Line Mutation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*