Genomic organization of the X-linked gene (PIG-A) that is mutated in paroxysmal nocturnal haemoglobinuria and of a related autosomal pseudogene mapped to 12q21

Hum Mol Genet. 1994 May;3(5):751-7. doi: 10.1093/hmg/3.5.751.

Abstract

The PIG-A gene, whose product is involved in one of the early steps in the synthesis of glycan phosphatidylinositol (GPI) anchors, has been recently found to be defective in all cases of paroxysmal nocturnal haemoglobinuria (PNH). By isolating genomic clones from a human phage library we now show that the PIG-A gene consists of six exons (the first of which is non-coding) spanning 17 kb of DNA, and we have mapped the gene to chromosomal position Xp22.1. The PIG-A promoter has features of a housekeeping gene. We have also isolated additional clones which cross-hybridize to PIG-A cDNA, and we have thus identified an intronless PIG-A pseudogene (psi PIG-A), which we have mapped to chromosomal position 12q21. psi PIG-A cannot be functional because it contains several stop codons and a frameshift. These data make it possible to design primers for amplification of the entire PIG-A coding region, with exclusion of psi PIG-A sequences, which will facilitate characterization of PIG-A mutations in patients with PNH. Database searches revealed that PIG-A contains homologies with a number of glycosyl transferases and is highly homologous (45%) to the protein encoded by the yeast SPT14 gene.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12*
  • DNA, Complementary / genetics
  • Exons
  • Genes
  • Hemoglobinuria, Paroxysmal / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Pseudogenes*
  • Saccharomyces cerevisiae / genetics
  • Salmonella typhimurium / genetics
  • Sequence Alignment
  • Sequence Homology
  • Species Specificity
  • Vertebrates / genetics
  • X Chromosome*

Substances

  • DNA, Complementary
  • Membrane Proteins
  • phosphatidylinositol glycan-class A protein

Associated data

  • GENBANK/X77457
  • GENBANK/X77724
  • GENBANK/X77725
  • GENBANK/X77726
  • GENBANK/X77727
  • GENBANK/X77728
  • GENBANK/X77729