Dominant and sporadic de novo disorders

Abstract

Abstract The genomic techniques developed in recent decades have advanced the field of genetics very rapidly by playing an essential role in identifying disease-causing variation, functionally characterizing many of the ~25,000 computationally annotated genes in the human genome, and elucidating important biological pathways in human health and disease. The study of dominantly inherited disorders has contributed significantly to our understanding of human diseases and traits, both rare and common. This chapter reviews and discusses how genomic techniques, including chromosomal microarray analysis, whole-exome sequencing, and whole-genome sequencing, have impacted our understanding of autosomal dominant and sporadic disease traits. Genomic sequencing of patients with sporadic disorders has revealed and highlighted the important role that de novo mutation plays in human disease. The different mechanisms by which pathogenic variation can lead to dominant and sporadic disorders, and the challenges associated with the study of these disorders, such as incomplete penetrance, are also discussed.