Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Dr., Building 101, MD D-201, Research Triangle Park, NC 27709, USA.
Oxid Med Cell Longev. 2013;2013:286524. doi: 10.1155/2013/286524. Epub 2013 Jul 10.
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 human NRF2 and its homologs in other vertebrate species. NRF2 is evolutionally conserved and shares sequence homology among species. Compilation of publically available SNPs and other genetic mutations shows that human NRF2 is 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 in NRF2 have led to oncogenic cell survival. Comprehensive information from the current review addresses association of NRF2 variation and disease phenotypes and supports the new insights into therapeutic strategies.
哺乳动物基因组的高密度图谱绘制使多种遗传研究成为可能，包括多基因性状的图谱绘制、数量性状位点的确定以及系统发育比较。对近交系小鼠品系的基因组测序分析确定了用于复杂性状研究的高密度单核苷酸多态性 (SNP)，这已成为研究人类疾病的生物医学的有用工具，可以缓解人类实验中的伦理和实际问题。核因子 (红细胞衍生 2)-样 2 (NRF2) 编码关键的宿主防御转录因子。本综述描述了人类 NRF2 及其在其他脊椎动物物种中的同源物的遗传特征。NRF2 在进化上是保守的，并且在物种间具有序列同源性。公共可用的 SNP 和其他遗传突变的编译表明，人类 NRF2 高度多态，每 72bp 发生一次诱变。在各种人类疾病中已经证明了功能危险等位基因和单倍型。此外，包括 NRF2 中的体细胞突变和失调的表观遗传过程在内的其他致病改变导致致癌细胞存活。本综述中的综合信息解决了 NRF2 变异与疾病表型的关联问题，并为治疗策略提供了新的见解。
