Abstract
BACKGROUND: Nonsyndromic cleft lip (CL) with or without cleft palate (CLP) is a common human birth defect with complex genetic etiology. One of the unidentified genes maps to chromosome 17q21. A mouse strain, A/WySn, has CLP with complex genetic etiology that models the human defect, and 1 of its causative genes, clf1, maps to a region homologous to human 17q21. Extensive studies of the candidate region pointed to a novel insertion of an IAP transposon 3′ from the gene Wnt9b as the clf1 mutation. Independently a recessive knockout mutation of Wnt9b (Wnt9b-) was reported to cause a lethal syndrome that includes some CLP. METHODS: A standard genetic test of allelism between clf1 and the Wnt9b- mutation was done. A total of 83 F1 embryos at gestation day 14 (GD 14) from Wnt9b-/+ males crossed with A/WySn females, and 79 BC1 GD 14 embryos from F1 Wnt9b-/clf1 males back-crossed to A/WySn females were observed for CL. Embryo genotypes at clf1 and Wnt9b were obtained from DNA markers. Genotypes for a second unlinked modifier locus from A/WySn, clf2, were similarly obtained. RESULTS: The compound mutant embryos (Wnt9b-/clf1) had high frequencies of CL: 27% in the F1 and 63% in the BC1. The clf2 modifier gene was found to have 3 alleles segregating in this study and to strongly influence the penetrance of CL in the compound mutant. CONCLUSIONS: The noncomplementation of clf1 and Wnt9b - confirms that clf1 is a mutation of the Wnt9b gene. The homologous human WNT9B gene and 3′ conserved noncoding region should be examined for a role in human nonsyndromic CLP.
Original language | English (US) |
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Pages (from-to) | 574-579 |
Number of pages | 6 |
Journal | Birth Defects Research Part A - Clinical and Molecular Teratology |
Volume | 76 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2006 |
Keywords
- Birth defect
- Cleft lip
- Cleft palate
- Gene
- Multifactorial
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Embryology
- Developmental Biology