A genome-wide scan for loci predisposing to non-syndromic cleft lip with or without cleft palate in two large Syrian families.
Non-syndromic cleft lip with/without cleft palate (CL/P) is a common, usually non-fatal birth defect of complex etiology. Several segregation analyses have demonstrated that genetic factors are important in the pathogenesis of CL/P, most likely through the interaction of several genes of modest effects. The aim of this study was to perform a genome-wide linkage analysis to identify/search for candidate gene loci for CL/P. We conducted a genome-wide search in two large, relatively isolated Syrian families, each one with a large number of cases with CL/P (18 in family 1 and 4 in family 2). A locus with a multipoint LOD score of 2.80 and a 2-point non-parametric MLS LOD of 3.0 was detected on 17p13.1. Other chromosomal regions with multipoint LOD scores > or = 1.2 (P < or = 0.01) included 3p21.2, 4q32.1, and 7q34. These data indicate the possible presence of several susceptibility loci for CL/P and identify a strong candidate locus for this common birth defect on chromosome 17p13.
Wyszynski
Diego F
DF
Genetics Program, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Albacha-Hejazi
Hasan
H
Aldirani
Mohammed
M
Hammod
Moustafa
M
Shkair
Hikmat
H
Karam
Ahmed
A
Alashkar
Jehad
J
Holmes
Taura N
TN
Pugh
Elizabeth W
EW
Doheny
Kimberly F
KF
McIntosh
Iain
I
Beaty
Terri H
TH
Bailey-Wilson
Joan E
JE
D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D020412:Multifactorial Inheritance / Q000235:genetics*; D013593:Syria; D020080:Tandem Repeat Sequences