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Gene Review

clf1  -  cleft lip 1

Mus musculus

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Disease relevance of clf1

 

High impact information on clf1

  • Cleft lip and palate is a common human birth defect, and its causes are being dissected through studies of human populations and through the use of animal models [6].
  • Cleft lip and palatal defects have been most extensively studied, but defects have also been noted in eyes, heart, and limb buds [7].
  • Human homologs of clf1 and clf2 are expected to be on 17q and 5q/9q [1].
  • A combination of new mapping panels (325 meioses), new markers, and a recombinant cleft lip embryo redefined the location of a recessive factor essential to cleft lip risk, clf1, and candidate genes Itgb3 and Crhr, to between D11Mit146/360 and D11Mit166/147 [1].
  • Cleft lip embryos recovered in 2.4% of 1485 first backcross (BC1) segregants from a cross of A/WySnJ (24% cleft lip) and C57BL/6J (no cleft lip) in A/WySnJ mothers, and in testcrosses of 10 recombinant inbred (RI) strains (AXB/Pgn or BXA/Pgn), were used for gene mapping and for inference of genetic architecture [1].
 

Biological context of clf1

  • A potentially homologous gene, clf1 on distal chromosome 11, is part of the digenic cause of the 10-30% CL(P) in the A/WySn mouse strain [8].
  • The ancestral pre-clf1 mutation haplotype was found in CBA/J mice [8].
 

Associations of clf1 with chemical compounds

 

Other interactions of clf1

  • Three single-nucleotide variants in A/WySn (vs. C57BL/6J) were found in each of the 3' untranslated regions (3'UTRs) of Wnt3 and of Wnt9b, respectively; their presence in CBA/J shows that none are the clf1 mutation [8].
  • This locus, here named clf1 (cleft lip) maps to Chromosome (Chr) 11 to a region having linkage homology with human 17q21-24, supporting reports of association of human CL(P) with the retinoic acid receptor alpha (RARA) locus [10].

References

  1. Unravelling the complex genetics of cleft lip in the mouse model. Juriloff, D.M., Harris, M.J., Brown, C.J. Mamm. Genome (2001) [Pubmed]
  2. Expression of Wnt9b and activation of canonical Wnt signaling during midfacial morphogenesis in mice. Lan, Y., Ryan, R.C., Zhang, Z., Bullard, S.A., Bush, J.O., Maltby, K.M., Lidral, A.C., Jiang, R. Dev. Dyn. (2006) [Pubmed]
  3. Major gene determination of liability to spontaneous cleft lip in the mouse. Biddle, F.G., Fraser, F.C. Journal of craniofacial genetics and developmental biology. Supplement. (1986) [Pubmed]
  4. Cleft lip and palate, sensorineural deafness, and sacral lipoma in two brothers: a possible example of the disorganisation mutant. Lowry, R.B., Yong, S.L. J. Med. Genet. (1991) [Pubmed]
  5. Experimental formation of cleft palate in mice with polychlorinated biphenyls (PCB). Watanabe, M., Sugahara, T. Toxicology (1981) [Pubmed]
  6. Cleft palate: players, pathways, and pursuits. Murray, J.C., Schutte, B.C. J. Clin. Invest. (2004) [Pubmed]
  7. Teratogenic effects of anticonvulsants. Paulson, G.W., Paulson, R.B. Arch. Neurol. (1981) [Pubmed]
  8. Investigations of the genomic region that contains the clf1 mutation, a causal gene in multifactorial cleft lip and palate in mice. Juriloff, D.M., Harris, M.J., Dewell, S.L., Brown, C.J., Mager, D.L., Gagnier, L., Mah, D.G. Birth defects research. Part A, Clinical and molecular teratology. (2005) [Pubmed]
  9. Cleft lip and palate in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: a morphological in vivo study. Yamada, T., Mishima, K., Fujiwara, K., Imura, H., Sugahara, T. Congenital anomalies. (2006) [Pubmed]
  10. The major locus for multifactorial nonsyndromic cleft lip maps to mouse chromosome 11. Juriloff, D.M., Mah, D.G. Mamm. Genome (1995) [Pubmed]
 
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