Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice

Nat Genet. 1994 Apr;6(4):357-62. doi: 10.1038/ng0494-357.

Abstract

Neural tube defects (NTD) in humans have been considered to have a multifactorial aetiology, however the participating genes have not been identified. The curly-tail (ct) mutant mouse develops NTD that resemble the human malformations in location, pathology and associated abnormalities. Moreover, there appears to be multifactorial influence on the incidence of NTD in offspring of curly-tail mice. We now describe a linkage analysis that localizes the ct gene to distal chromosome 4 in mice. Further analysis using recombinant inbred strains demonstrates the presence of at least three modifier loci that influence the incidence of NTD. This study provides definitive evidence for multifactorial inheritance in a mouse model of human NTD.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / embryology
  • Abnormalities, Multiple / genetics*
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Crosses, Genetic
  • Disease Models, Animal*
  • Endoderm / pathology
  • Epistasis, Genetic*
  • Genes*
  • Lod Score
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred Strains / embryology
  • Mice, Inbred Strains / genetics*
  • Mice, Mutant Strains / embryology
  • Mice, Mutant Strains / genetics*
  • Molecular Sequence Data
  • Muridae / genetics
  • Neural Tube Defects / genetics*
  • Spinal Dysraphism / embryology
  • Spinal Dysraphism / genetics*
  • Spinal Dysraphism / physiopathology
  • Stress, Mechanical
  • Tail / abnormalities*
  • Tail / embryology