BACKGROUND: Clefts of the lip and palate are common birth defects, affecting approximately 1 in 700 births worldwide. The aetiology of clefting is complex, with multiple genetic and environmental influences. METHODS: Genotype based linkage disequilibrium analysis was conducted using the family based association test (FBAT) and the likelihood ratio test (LRT). We also carried out direct sequencing of the PVR and PVRL2 candidate genes based on their homology to PVRL1, a gene shown previously to cause Margarita Island clefting. Participants included 434 patients with cleft lip with or without cleft palate or cleft palate only and their mothers from eight countries in South America, 205 nuclear triads (father-mother-affected child) from Iowa, 541 nuclear triads from Denmark, and 100 patients with cleft lip and palate from the Philippines. RESULTS: An allelic variant in the PVR gene showed statistically significant association with both South American and Iowa populations (p = 0.0007 and p = 0.0009, respectively). Direct sequencing of PVR and PVRL2 yielded 26 variants, including two rare amino acid changes, one in each gene, which were not seen in controls. CONCLUSIONS: We found an association between a common variant in a gene at 19q and isolated clefting in two heterogeneous populations. However, it is unclear from our data if rare variants in PVR and PVRL2 are sufficient to cause clefting in isolation.
BACKGROUND:Clefts of the lip and palate are common birth defects, affecting approximately 1 in 700 births worldwide. The aetiology of clefting is complex, with multiple genetic and environmental influences. METHODS: Genotype based linkage disequilibrium analysis was conducted using the family based association test (FBAT) and the likelihood ratio test (LRT). We also carried out direct sequencing of the PVR and PVRL2 candidate genes based on their homology to PVRL1, a gene shown previously to cause Margarita Island clefting. Participants included 434 patients with cleft lip with or without cleft palate or cleft palate only and their mothers from eight countries in South America, 205 nuclear triads (father-mother-affected child) from Iowa, 541 nuclear triads from Denmark, and 100 patients with cleft lip and palate from the Philippines. RESULTS: An allelic variant in the PVR gene showed statistically significant association with both South American and Iowa populations (p = 0.0007 and p = 0.0009, respectively). Direct sequencing of PVR and PVRL2 yielded 26 variants, including two rare amino acid changes, one in each gene, which were not seen in controls. CONCLUSIONS: We found an association between a common variant in a gene at 19q and isolated clefting in two heterogeneous populations. However, it is unclear from our data if rare variants in PVR and PVRL2 are sufficient to cause clefting in isolation.
Authors: K Ranade; M S Chang; C T Ting; D Pei; C F Hsiao; M Olivier; R Pesich; J Hebert; Y D Chen; V J Dzau; D Curb; R Olshen; N Risch; D R Cox; D Botstein Journal: Genome Res Date: 2001-07 Impact factor: 9.043
Authors: Mary L Marazita; L Leigh Field; Margaret E Cooper; Rose Tobias; Brion S Maher; Supakit Peanchitlertkajorn; You-e Liu Journal: Cleft Palate Craniofac J Date: 2002-03
Authors: Mary L Marazita; L Leigh Field; Margaret E Cooper; Rose Tobias; Brion S Maher; Supakit Peanchitlertkajorn; You-e Liu Journal: Am J Hum Genet Date: 2002-06-26 Impact factor: 11.025
Authors: Alexandre R Vieira; Toby G McHenry; Sandra Daack-Hirsch; Jeffrey C Murray; Mary L Marazita Journal: Am J Med Genet A Date: 2008-06-01 Impact factor: 2.802
Authors: Alexandre R Vieira; Toby G McHenry; Sandra Daack-Hirsch; Jeffrey C Murray; Mary L Marazita Journal: Genet Med Date: 2008-09 Impact factor: 8.822