Non-coding genetic variants in human disease.

TitleNon-coding genetic variants in human disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsZhang, F, Lupski, JR
JournalHum Mol Genet
Volume24
IssueR1
PaginationR102-10
Date Published2015 Oct 15
ISSN0964-6906
KeywordsAnimals, Disease, DNA Copy Number Variations, Genetic Variation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid
Abstract

Genetic variants, including single-nucleotide variants (SNVs) and copy number variants (CNVs), in the non-coding regions of the human genome can play an important role in human traits and complex diseases. Most of the genome-wide association study (GWAS) signals map to non-coding regions and potentially point to non-coding variants, whereas their functional interpretation is challenging. In this review, we discuss the human non-coding variants and their contributions to human diseases in the following four parts. (i) Functional annotations of non-coding SNPs mapped by GWAS: we discuss recent progress revealing some of the molecular mechanisms for GWAS signals affecting gene function. (ii) Technical progress in interpretation of non-coding variants: we briefly describe some of the technologies for functional annotations of non-coding variants, including the methods for genome-wide mapping of chromatin interaction, computational tools for functional predictions and the new genome editing technologies useful for dissecting potential functional consequences of non-coding variants. (iii) Non-coding CNVs in human diseases: we review our emerging understanding the role of non-coding CNVs in human disease. (iv) Compound inheritance of large genomic deletions and non-coding variants: compound inheritance at a locus consisting of coding variants plus non-coding ones is described.

DOI10.1093/hmg/ddv259
Alternate JournalHum. Mol. Genet.
PubMed ID26152199
PubMed Central IDPMC4572001
Grant ListR01GM106373 / GM / NIGMS NIH HHS / United States
R01NS058529 / NS / NINDS NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
U54HD083092 / HD / NICHD NIH HHS / United States
R01 GM106373 / GM / NIGMS NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States