Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results

M. L. Marazita; A. C. Lidral; J. C. Murray; L. L. Field; B. S. Maher; T. Goldstein McHenry; M. E. Cooper; M. Govil; Sandra Daack-Hirsch; B. Riley; A. Jugessur; T. Felix; L. Morene; M. A. Mansilla; A. R. Vieira; K. Doheny; E. Pugh; C. Valencia-Ramirez; M. Arcos-Burgos

doi:10.1159/000224636

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Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results

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Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results

M. L. Marazita, A. C. Lidral, J. C. Murray, L. L. Field, B. S. Maher, T. Goldstein McHenry, M. E. Cooper, M. Govil, Sandra Daack-Hirsch, B. Riley, …

Human heredity, Vol.68(3), pp.151-170

01/01/2009

DOI: 10.1159/000224636

PMID: 19521098

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Published (Version of record)Human heredity, 68:3 (2009) pp.151-170.

Abstract

<p>OBJECTIVES: Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P). METHODS: We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results. RESULTS: Significant (multipoint HLOD >or=3.2) or genome-wide-significant (HLOD >or=4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in IRF6 (1q32) and in or near FOXE1 (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the IRF6 region results were most significant for families in which affected individuals have CL alone, and the FOXE1 region results were most significant in families in which some or all of the affected individuals have CL with CP. CONCLUSIONS: These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P.</p>

Nursing

Phenotype

Chromosome Mapping

Chromosomes

Human/genetics

Cleft Lip/genetics

Cleft Palate/genetics

Genetic Linkage

Genetic Predisposition to Disease

Genome

Human

Genome-Wide Association Study

Humans

Polymorphism

Single Nucleotide

Details

Title: Subtitle: Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results
Creators: M. L. Marazita
A. C. Lidral
J. C. Murray
L. L. Field
B. S. Maher
T. Goldstein McHenry
M. E. Cooper
M. Govil
Sandra Daack-Hirsch - University of Iowa
B. Riley
A. Jugessur
T. Felix
L. Morene
M. A. Mansilla
A. R. Vieira
K. Doheny
E. Pugh
C. Valencia-Ramirez
M. Arcos-Burgos
Resource Type: Journal article
Publication Details: Human heredity, Vol.68(3), pp.151-170
DOI: 10.1159/000224636
PMID: 19521098
NLM abbreviation: Hum Hered
ISSN: 1423-0062
Language: English
Date published: 01/01/2009
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research; Iowa Institute of Human Genetics
Record Identifier: 9983557359402771

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