Autosomal dominant nonsyndromic cleft lip and palate: significant evidence of linkage at 18q21.1.
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. Nonparametric 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).
Beiraghi
Soraya
S
Division of Pediatric Dentistry, University of Minnesota, Minneapolis, MN, USA.
Nath
Swapan K
SK
Gaines
Matthew
M
Mandhyan
Desh D
DD
Hutchings
David
D
Ratnamala
Uppala
U
McElreavey
Ken
K
Bartoloni
Lucia
L
Antonarakis
Gregory S
GS
Antonarakis
Stylianos E
SE
Radhakrishna
Uppala
U
D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D008040:Genetic Linkage; D023281:Genomics; D006801:Humans; D008126:Lod Score; D010375:Pedigree; D011110:Polymorphism, Genetic