Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35.
Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region at 9q21 (heterogeneity LOD score [HLOD]=6.6). In addition, meta-analyses with the addition of results from 186 more families (six populations; 1,033 genotyped individuals) showed genomewide significance for 10 more regions, including another novel region at 2q32-35 (P=.0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder.
Marazita
Mary L
ML
Center for Craniofacial and Dental Genetics, Division of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA. marazita@sdmgenetics.pitt.edu
Murray
Jeffrey C
JC
Lidral
Andrew C
AC
Arcos-Burgos
Mauricio
M
Cooper
Margaret E
ME
Goldstein
Toby
T
Maher
Brion S
BS
Daack-Hirsch
Sandra
S
Schultz
Rebecca
R
Mansilla
M Adela
MA
Field
L Leigh
LL
Liu
You-e
YE
Prescott
Natalie
N
Malcolm
Sue
S
Winter
Robin
R
Ray
Ajit
A
Moreno
Lina
L
Valencia
Consuelo
C
Neiswanger
Katherine
K
Wyszynski
Diego F
DF
Bailey-Wilson
Joan E
JE
Albacha-Hejazi
Hasan
H
Beaty
Terri H
TH
McIntosh
Iain
I
Hetmanski
Jacqueline B
JB
Tunçbilek
Gökhan
G
Edwards
Matthew
M
Harkin
Louise
L
Scott
Rodney
R
Roddick
Laurence G
LG
D002889:Chromosomes, Human, Pair 2; D002899:Chromosomes, Human, Pair 9; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score
D005819:Genetic Markers