Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used ∼10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL > 3.5; P < .005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL = 5.57; P = .00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (α = 100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of ∼20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families. © 2006 by The American Society of Human Genetics. All rights reserved.
CITATION STYLE
Radhakrishna, U., Ratnamala, U., Gaines, M., Beiraghi, S., Hutchings, D., Golla, J., … Nath, S. K. (2006). Genomewide scan for nonsyndromic cleft lip and palate in multigenerational Indian families reveals significant evidence of linkage at 13q33.1-34. American Journal of Human Genetics, 79(3), 580–585. https://doi.org/10.1086/507487
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