title: Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin.
abstract: Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome-wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC). The sample included 74 NSCL/P families, 15 NSCPO families, and 2 mixed families (a total of 217 affected and 230 unaffected individuals were genotyped). We genotyped 542 microsatellite markers (average intermarker distance = 6.9 cM). Multipoint nonparametric linkage analysis was performed using Allegro 2.0f. In addition to the factors investigated in previous genome-wide linkage analyses, we searched for sex-specific susceptibility loci, loci demonstrating parental imprinting and loci that are shared by NSCL/P and NSCPO. Several genomic regions likely to contain susceptibility loci for NSC were identified at the level of nominal significance. Some of these overlap with regions identified in previous studies. Suggestive evidence of linkage was obtained for the loci 4q21-q26 and 1p31-p21, with the chromosome 1 locus showing a male-specific genetic effect. Our study has identified promising chromosomal regions for the identification of NSC-associated genes, and demonstrates the importance of performing detailed statistical analyses which take into account complex genetic mechanisms such as sex-specific effects and genomic imprinting. Further research in large patient samples is necessary to identify factors common to NSCL/P and NSCPO.
authors: Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany. e.mangold@uni-bonn.de
authors: Elisabeth
authors: E
authors: Mangold
authors: Heiko
authors: H
authors: Reutter
authors: Stefanie
authors: S
authors: Birnbaum
authors: Maja
authors: M
authors: Walier
authors: Manuel
authors: M
authors: Mattheisen
authors: Henning
authors: H
authors: Henschke
authors: Carola
authors: C
authors: Lauster
authors: Gül
authors: G
authors: Schmidt
authors: Franziska
authors: F
authors: Schiefke
authors: Rudolf H
authors: RH
authors: Reich
authors: Martin
authors: M
authors: Scheer
authors: Alexander
authors: A
authors: Hemprich
authors: Markus
authors: M
authors: Martini
authors: Bert
authors: B
authors: Braumann
authors: Michael
authors: M
authors: Krimmel
authors: Charlotte
authors: C
authors: Opitz
authors: Jan-Hendrik
authors: JH
authors: Lenz
authors: Franz-Josef
authors: FJ
authors: Kramer
authors: Thomas F
authors: TF
authors: Wienker
authors: Markus M
authors: MM
authors: Nöthen
authors: Amalia
authors: A
authors: Diaz Lacava
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005190:Family; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010375:Pedigree; D044465:White People / Q000235:genetics*