title: Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35.
abstract: 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.
authors.affiliation: 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
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Lidral
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arcos-Burgos
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Toby
authors.initials: T
authors.lastname: Goldstein
authors.forename: Brion S
authors.initials: BS
authors.lastname: Maher
authors.forename: Sandra
authors.initials: S
authors.lastname: Daack-Hirsch
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schultz
authors.forename: M Adela
authors.initials: MA
authors.lastname: Mansilla
authors.forename: L Leigh
authors.initials: LL
authors.lastname: Field
authors.forename: You-e
authors.initials: YE
authors.lastname: Liu
authors.forename: Natalie
authors.initials: N
authors.lastname: Prescott
authors.forename: Sue
authors.initials: S
authors.lastname: Malcolm
authors.forename: Robin
authors.initials: R
authors.lastname: Winter
authors.forename: Ajit
authors.initials: A
authors.lastname: Ray
authors.forename: Lina
authors.initials: L
authors.lastname: Moreno
authors.forename: Consuelo
authors.initials: C
authors.lastname: Valencia
authors.forename: Katherine
authors.initials: K
authors.lastname: Neiswanger
authors.forename: Diego F
authors.initials: DF
authors.lastname: Wyszynski
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Hasan
authors.initials: H
authors.lastname: Albacha-Hejazi
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Iain
authors.initials: I
authors.lastname: McIntosh
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Gökhan
authors.initials: G
authors.lastname: Tunçbilek
authors.forename: Matthew
authors.initials: M
authors.lastname: Edwards
authors.forename: Louise
authors.initials: L
authors.lastname: Harkin
authors.forename: Rodney
authors.initials: R
authors.lastname: Scott
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Roddick
mesh_terms: 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
chemical_list: D005819:Genetic Markers