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.
- non-coding DNA
- limb defects
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Contributors KN was responsible for drafting, writing of the manuscript, preparing the figures and corrections. EH-K was responsible for drafting, writing, preparing the table and corrections. PT was responsible for drafting, writing and corrections.
Funding This work was supported by the Polish National Science Centre (PRO-2013/11/B/NZ4/03660 to PT, UMO-2015/19/B/NZ4/03184 to PT, and PRO-2017/27/N/NZ5/02940 to EH-K).
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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