Title

Hotspots of Human Mutation.

Document Type

Article

Publication Date

8-1-2021

Publication Title

Trends in genetics : TIG

Keywords

JGM, DNA Replication, Genome, Human, Genomic Structural Variation, Genomics, Humans, Mutation, Polymorphism, Single Nucleotide, Recombination, Genetic

JAX Source

Trends Genet 2021 Aug; 37(8):717-729

Volume

37

Issue

8

First Page

717

Last Page

729

ISSN

0168-9525

PMID

33199048

DOI

https://doi.org/10.1016/j.tig.2020.10.003

Grant

GM120453, GM133600

Abstract

Mutation of the human genome results in three classes of genomic variation: single nucleotide variants; short insertions or deletions; and large structural variants (SVs). Some mutations occur during normal processes, such as meiotic recombination or B cell development, and others result from DNA replication or aberrant repair of breaks in sequence-specific contexts. Regardless of mechanism, mutations are subject to selection, and some hotspots can manifest in disease. Here, we discuss genomic regions prone to mutation, mechanisms contributing to mutation susceptibility, and the processes leading to their accumulation in normal and somatic genomes. With further, more accurate human genome sequencing, additional mutation hotspots, mechanistic details of their formation, and the relevance of hotspots to evolution and disease are likely to be discovered.

Comments

We thank the members of the Beck lab and colleagues at the Jackson Laboratory for Genomic Medicine for reading and editing the review; in particular we appreciated input from Francesca Menghi and Samirkumar B. Amin.

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