Manuel Mattheisen

Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Elisabeth Mangold
  • ,
  • Heiko Reutter
  • ,
  • Stefanie Birnbaum
  • ,
  • Maja Walier
  • ,
  • Manuel Mattheisen
  • Henning Henschke
  • ,
  • Carola Lauster
  • ,
  • Gül Schmidt
  • ,
  • Franziska Schiefke
  • ,
  • Rudolf H Reich
  • ,
  • Martin Scheer
  • ,
  • Alexander Hemprich
  • ,
  • Markus Martini
  • ,
  • Bert Braumann
  • ,
  • Michael Krimmel
  • ,
  • Charlotte Opitz
  • ,
  • Jan-Hendrik Lenz
  • ,
  • Franz-Josef Kramer
  • ,
  • Thomas F Wienker
  • ,
  • Markus M Nöthen
  • ,
  • Amalia Diaz Lacava
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.
Original languageEnglish
JournalAmerican Journal of Medical Genetics. Part A
Volume149A
Issue12
Pages (from-to)2680-94
Number of pages15
ISSN1552-4825
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

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