Genomic Structure and Variation of Nuclear Factor (Erythroid-Derived 2)-Like 2

Abstract

High-density mapping of mammalian genomes has enabled a wide range of genetic investigations including the mapping of polygenic traits, determination of quantitative trait loci, and phylogenetic comparison. Genome sequencing analysis of inbred mouse strains has identified high-density single nucleotide polymorphisms (SNPs) for investigation of complex traits, which has become a useful tool for biomedical research of human disease to alleviate ethical and practical problems of experimentation in humans. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) encodes a key host defense transcription factor. This review describes genetic characteristics of humanNRF2and its homologs in other vertebrate species.NRF2is evolutionally conserved and shares sequence homology among species. Compilation of publically available SNPs and other genetic mutations shows that humanNRF2is highly polymorphic with a mutagenic frequency of 1 per every 72 bp. Functional at-risk alleles and haplotypes have been demonstrated in various human disorders. In addition, other pathogenic alterations including somatic mutations and misregulated epigenetic processes inNRF2have led to oncogenic cell survival. Comprehensive information from the current review addresses association ofNRF2variation and disease phenotypes and supports the new insights into therapeutic strategies.