Mapping Data

Experiment

• Experiment
  TEXT-Genetic Cross
• Chromosome
  13
• Reference
  J:69826 Juriloff DM, et al., Unravelling the complex genetics of cleft lip in the mouse model. Mamm Genome. 2001 Jun;12(6):426-35
• ID
  MGI:3497781

Genes

Gene	Assay Type
clf2	visible phenotype
D13Mit13	PCR
D13Mit54	PCR
D13Mit231	PCR
Neurog1
Pitx1
Smad5
Ptch1
Rab24
Lect2
Tgfbi

Notes

• Experiment
  A population of A/WySnJ x (C57BL/6J x A/WySnJ)F1 backcross embryos were used to map genes responsible for susceptibility to cleft lip and palate. Inbred A strains, such as A/J, A/WySnJ, and A/HeJ exhibit increased incidence of cleft lip and palate (5%-30%) compared to other inbred strains such as C57BL/6J. A maternal effect is also apparents as backcross embryos from A/WySnJ mothers exhibit increased incidence of cleft lip and palate compared to when the mother is a (C57BL/6J x A/WySnJ)F1 hybrid.
  
  The clf1 gene maps to approximately 63 cM on mouse Chromosome 11 near D11Mit10. All backcross embryos with cleft lip and palate were homozygous for A/WySnJ-derived alleles at D11Mit10. This locus appears to be recessive in nature. The clf1 candidate region is a 2 cM interval flanked by markers D11Mit146 and D11Mit147. Potential candidate genes mapping to this interval are Wnt9b (63 cM), Wnt3 (63 cM), Crhr1 (62 cM), Mapt (64 cM), Itgb3 (68 cM), Dlx3, and Dlx4. This interval is syntenic to a region of human Chromosome 17q that shows association to some cases of human cleft lip and palate.
  
  The clf2 gene maps to approximately 35 cM on mouse Chromosome 13 near D13Mit13. The clf2 interval is flanked by markers D13Mit54 (35 cM) and D13Mit231 (39 cM). The cleft lip and palate phenotype shows tight linkage to homozygosity for A/WySnJ-derived alleles at Neurog1 (35 cM). Heterozygosity at clf2 in conjunction with homozygosity for A/WySnJ-derived alleles at clf1 is associated with a slight increase in susceptibility to cleft lip and palate. Potential candidate genes for clf2 include Pitx1 (34 cM), Smad5 (35 cM), Ptch1 (36 cM), Rab24 (36 cM), Lect2 (37 cM), and Tgfbi (38 cM).
  
  The highest risk for cleft lip and palate is seen in animals homozygous for A/WySnJ-derived alleles at both clf1 and clf2.
  
  A third cleft lip and palate gene, tentatively named clf3, is thought to exist but requires further investigation. This locus could modify clf1 and clf2 and potentially maps to distal mouse Chromosome 18, proximal mouse Chromosome 7, or proximal mouse Chromosome 11.