Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene

Eur J Hum Genet. 1993;1(1):30-6. doi: 10.1159/000472385.

Abstract

A de novo insertion of an Alu repeated DNA element was found within exon V of the factor IX gene in a patient with severe haemophilia B. The element interrupts the reading frame of the mature factor IX at glutamic acid 96 resulting in a stop codon within the inserted sequence. The Alu repeat is 322 bp long, and the 5' region is shortened by 38 bp. The insertion created a target site duplication of 15 bp consistent with retroposition, and contains a pure polyadenine tract of at least 78 resides at the 3' end. The nucleotide sequence agrees with a consensus for an Alu subfamily which is evolutionarily the most recently inserted, suggesting that it is an exact copy of a putative source gene. These observations indicate that retroposition of Alu elements is a continual process and a mechanism for generating human genetic defects.

Publication types

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

MeSH terms

  • Base Sequence
  • Consensus Sequence
  • DNA Mutational Analysis
  • Exons
  • Factor IX / genetics*
  • Genes
  • Hemophilia B / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • X Chromosome

Substances

  • Factor IX