Autosomal dominant nonsyndromic cleft lip and palate: Significant evidence of linkage at 18q21.1

Soraya Beiraghi, Swapan K. Nath, Matthew Gaines, Desh D. Mandhyan, David Hutchings, Uppala Ratnamala, Ken McElreavey, Lucia Bartoloni, Gregory S. Antonarakis, Stylianos E. Antonarakis, Uppala Radhakrishna

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15 Scopus citations


Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700-1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide-polymorphism array. Non-parametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL = 43.33 and P = .000061; nonparametric LOD = 3.97 and P = .00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7-Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high-risk variant for NSCL/P in this family; we propose to name this locus "OFC11" (orofacial cleft 11).

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - Jul 2007

Bibliographical note

Funding Information:
We thank the members of family UR410 for their cooperation in the study. The study was supported in part by the Green Cross Blood Bank, Ahmedabad, Gujarat, India. K.M. is supported by a GIS-Institut des Maladies Rare grant. The laboratory of S.E.A. is supported by the Swiss National Science Foundation. S.K.N. was supported by Oklahoma Medical Research Foundation institutional grant 9124, for linkage analysis.


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