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Genome‐wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin
Author(s) -
Mangold Elisabeth,
Reutter Heiko,
Birnbaum Stefanie,
Walier Maja,
Mattheisen Manuel,
Henschke Henning,
Lauster Carola,
Schmidt Gül,
Schiefke Franziska,
Reich Rudolf H.,
Scheer Martin,
Hemprich Alexander,
Martini Markus,
Braumann Bert,
Krimmel Michael,
Opitz Charlotte,
Lenz JanHendrik,
Kramer FranzJosef,
Wienker Thomas F.,
Nöthen Markus M.,
Diaz Lacava Amalia
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33136
Subject(s) - genetics , locus (genetics) , genome scan , genetic linkage , biology , microsatellite , genome , linkage (software) , imprinting (psychology) , gene , allele
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. © 2009 Wiley‐Liss, Inc.