Nonhomologous recombination in the human genome: deletions in the human factor VIII gene

Genomics. 1991 May;10(1):94-101. doi: 10.1016/0888-7543(91)90489-2.

Abstract

Four deletions in the human factor VIII gene have been characterized at the sequence level in patients with hemophilia A. Deletion JH 1 extends 57 kb from IVS 10 to IVS 18. Intron 13 and exon 14 are partially deleted in patients JH 7 and JH 37, with a loss of 3.2 and 2.4 kb of DNA, respectively. The 3' deletion breakpoint of the JH 21 event resides in intron 3 and extends 5' into intron 1, resulting in the loss of exons 2 and 3. Seven of the eight breakpoints sequenced (5' and 3' for each of the four deletions) occur in nonrepetitive sequence, while the 3' breakpoint of the JH 1 resides in an Alu repetitive element. All of the deletions are the result of nonhomologous recombination. The 5' and 3' breakpoints of JH 1, JH 7, and JH 37 share 2- to 3-bp homologies at the deletion junctions. In contrast, two nucleotides have been inserted at the JH 21 deletion junction. Short sequence homologies may facilitate end-joining reactions in nonhomologous recombination events.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Chromosome Deletion*
  • DNA
  • Exons
  • Factor VIII / genetics*
  • Genome, Human
  • Hemophilia A / genetics*
  • Humans
  • Introns
  • Molecular Sequence Data
  • Recombination, Genetic*
  • Restriction Mapping

Substances

  • Factor VIII
  • DNA

Associated data

  • GENBANK/M63313
  • GENBANK/M63314
  • GENBANK/M63315
  • GENBANK/M63316
  • GENBANK/M63317
  • GENBANK/M63318
  • GENBANK/M63319
  • GENBANK/M63320
  • GENBANK/M63321
  • GENBANK/M63322