Genomic disorders 20 years on - mechanisms for clinical manifestations.

Genomic disorders 20 years on - mechanisms for clinical manifestations.
Clin Genet. 2017 Sep 26;:
Authors: Harel T, Lupski JR
Abstract
Genomic disorders result from copy number variants (CNVs) or submicroscopic rearrangements of the genome rather than from single nucleotide variants (SNVs). Diverse technologies, including array comparative genomic hybridization (aCGH) and, more recently, whole genome sequencing and whole exome sequencing, have enabled robust genome-wide unbiased detection of CNVs in affected individuals and in reportedly healthy controls. Sequencing of breakpoint junctions has allowed for elucidation of upstream mechanisms leading to genomic instability and resultant structural variation, whereas studies of the association between CNVs and specific diseases or susceptibility to morbid traits have enhanced our understanding of the downstream effects. In this review, we discuss the hallmarks of genomic disorders as they were defined during the first decade of the field, including genomic instability and the mechanism for rearrangement defined as nonallelic homologous recombination (NAHR); recurrent versus nonrecurrent rearrangements; and gene dosage sensitivity. Moreover, we highlight the exciting advances of the second decade of this field, including a deeper understanding of genomic instability and the mechanisms underlying complex rearrangements, mechanisms for constitutional and somatic chromosomal rearrangements, ...

Source: Clinical Genetics - September 26, 2017 Category: Genetics & Stem Cells Authors: Harel T, Lupski JR Tags: Clin Genet Source Type: research