Genomic organization of the UGT2b gene cluster on human chromosome 4q13

Pharmacogenetics. 2000 Apr;10(3):251-60. doi: 10.1097/00008571-200004000-00006.

Abstract

The UDP-glucuronosyltransferases (UGTs) comprise a large family of proteins capable of detoxifying a wide variety of both endogenous and exogenous substrates. The primary function of this gene superfamily is to catalyze the glycosylation of substrates such as biogenic amines, steroids, bile acids, phenolic compounds and various other pharmacologically relevant compounds, including numerous carcinogens, toxic environmental pollutants and prescription drugs. This conjugation increases the solubility of these compounds, allowing them to be excreted more readily through hepatic or renal mechanisms. This paper describes the genomic characterization and chromosomal localization of three UGT2B genes which together comprise part of a large cluster of related sequences, including pseudogenes found on human chromosome 4q13. A genomic map spanning approximately 500-1000 kb of this region reveals the presence of three previously described UGT2B genes, at least two previously uncharacterized pseudogenes and a significant number of remnant gene fragments and places UGT2B4 between UGT2B7 and UGT2B15. Additionally, access to a large reference DNA bank allowed us to calculate allele frequencies for two UGT2B SNPs: D85R in UGT2B15 and Q458D in UGT2B4 amongst 803 unrelated individuals representing five ethnic populations. The data presented here suggest a recent evolutionary history of gene duplication, mutation and rearrangement. Furthermore, they suggest that a re-evaluation of the current description of the UGT2B gene family with respect to the number of specific genes, degree of allelic diversity and molecular evolution may be necessary.

MeSH terms

  • Biological Evolution
  • Chromosome Mapping
  • Chromosomes, Human, Pair 4 / genetics*
  • Ethnic Groups / genetics
  • Gene Frequency
  • Genomic Library
  • Glucuronosyltransferase / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Isoenzymes / genetics
  • Multigene Family*
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Pseudogenes

Substances

  • Isoenzymes
  • Glucuronosyltransferase