Genetic evidence for the role of loci at 19q13 in cleft lip and palate

A Warrington; A R Vieira; K Christensen; I M Orioli; E E Castilla; P A Romitti; J C Murray

doi:10.1136/jmg.2005.034785

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Genetic evidence for the role of loci at 19q13 in cleft lip and palate

Journal article

Open access

Peer reviewed

Genetic evidence for the role of loci at 19q13 in cleft lip and palate

A Warrington, A R Vieira, K Christensen, I M Orioli, E E Castilla, P A Romitti and J C Murray

Journal of medical genetics, Vol.43(6), pp.e26-e26

06/2006

DOI: 10.1136/jmg.2005.034785

PMCID: PMC2564544

PMID: 16740910

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Abstract

Clefts of the lip and palate are common birth defects, affecting approximately 1 in 700 births worldwide. The aetiology of clefting is complex, with multiple genetic and environmental influences. Genotype based linkage disequilibrium analysis was conducted using the family based association test (FBAT) and the likelihood ratio test (LRT). We also carried out direct sequencing of the PVR and PVRL2 candidate genes based on their homology to PVRL1, a gene shown previously to cause Margarita Island clefting. Participants included 434 patients with cleft lip with or without cleft palate or cleft palate only and their mothers from eight countries in South America, 205 nuclear triads (father-mother-affected child) from Iowa, 541 nuclear triads from Denmark, and 100 patients with cleft lip and palate from the Philippines. An allelic variant in the PVR gene showed statistically significant association with both South American and Iowa populations (p = 0.0007 and p = 0.0009, respectively). Direct sequencing of PVR and PVRL2 yielded 26 variants, including two rare amino acid changes, one in each gene, which were not seen in controls. We found an association between a common variant in a gene at 19q and isolated clefting in two heterogeneous populations. However, it is unclear from our data if rare variants in PVR and PVRL2 are sufficient to cause clefting in isolation.

Cleft Palate - diagnosis

Cleft Lip - diagnosis

Cell Adhesion Molecules

Humans

Membrane Glycoproteins - chemistry

Molecular Sequence Data

Male

Cleft Palate - genetics

Receptors, Virus - genetics

Nectins

Genetic Variation

South America - ethnology

DNA Mutational Analysis

Female

Amino Acid Sequence

Membrane Proteins - genetics

Gene Frequency

Iowa - ethnology

Chromosome Mapping

Linkage Disequilibrium

Membrane Glycoproteins - genetics

Chromosomes, Human, Pair 19

Cleft Lip - genetics

Sequence Alignment

Alleles

Details

Title: Subtitle: Genetic evidence for the role of loci at 19q13 in cleft lip and palate
Creators: A Warrington
A R Vieira
K Christensen
I M Orioli
E E Castilla
P A Romitti
J C Murray
Resource Type: Journal article
Publication Details: Journal of medical genetics, Vol.43(6), pp.e26-e26
DOI: 10.1136/jmg.2005.034785
PMID: 16740910
PMCID: PMC2564544
NLM abbreviation: J Med Genet
ISSN: 1468-6244
eISSN: 1468-6244
Publisher: England
Grant note: P50 DE016215 / NIDCR NIH HHS D43 TW005503 / FIC NIH HHS R01 DE008559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS R01 DE011948 / NIDCR NIH HHS DE 08559 / NIDCR NIH HHS R01 DE 11948 / NIDCR NIH HHS 5 D43 TW05503 / FIC NIH HHS
Language: English
Date published: 06/2006
Academic Unit: Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Biostatistics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research
Record Identifier: 9983995173002771

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