%0 Journal Article
%T Mutations in gene regulatory elements linked to human limb malformations.
%A Nowosad K
%A Hordyjewska-Kowalczyk E
%A Tylzanowski P
%J J Med Genet
%V 57
%N 6
%D 06 2020
%M 31857429
%F 5.941
%R 10.1136/jmedgenet-2019-106369
%X Most of the human genome has a regulatory function in gene expression. The technological progress made in recent years permitted the revision of old and discovery of new mutations outside of the protein-coding regions that do affect human limb morphology. Steadily increasing discovery rate of such mutations suggests that until now the largely neglected part of the genome rises to its well-deserved prominence. In this review, we describe the recent technological advances permitting this unprecedented advance in identifying non-coding mutations. We especially focus on the mutations in cis-regulatory elements such as enhancers, and trans-regulatory elements such as miRNA and long non-coding RNA, linked to hereditary or inborn limb defects. We also discuss the role of chromatin organisation and enhancer-promoter interactions in the aetiology of limb malformations.