Choi, SJ and Marazita, ML and Hart, SP and Sulima, PP and Field, LL and McHenry, TG and Govil, M and Cooper, ME and Letra, A and Menezes, R and Narayanan, S and Mansilla, MA and Granjeiro, JM and Vieira, AR and Lidral, AC and Murray, JC and Hart, TC
(2009)
The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P.
European Journal of Human Genetics, 17 (6).
774 - 784.
ISSN 1018-4813
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Abstract
Human linkage and association studies suggest a gene(s) for nonsyndromic cleft lip with or without cleft palate (CL/P) on chromosome 4q31-q32 at or near the platelet-derived growth factor-C (PDGF-C) locus. The mouse Pdgfc-/- knockout shows that PDGF-C is essential for palatogenesis. To evaluate the role of PDGF-C in human clefting, we performed sequence analysis and SNP genotyping using 1048 multiplex CL/P families and 1000 case-control samples from multiple geographic origins. No coding region mutations were identified, but a novel -986 C>T SNP (rs28999109) was significantly associated with CL/P (P=0.01) in cases from Chinese families yielding evidence of linkage to 4q31-q32. Significant or near-significant association was also seen for this and several other PDGF-C SNPs in families from the United States, Spain, India, Turkey, China, and Colombia, whereas no association was seen in families from the Philippines, and Guatemala, and case-controls from Brazil. The -986T allele abolished six overlapping potential transcription regulatory motifs. Transfection assays of PDGF-C promoter reporter constructs show that the -986T allele is associated with a significant decrease (up to 80%) of PDGF-C gene promoter activity. This functional polymorphism acting on a susceptible genetic background may represent a component of human CL/P etiology.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Choi, SJ | | | | Marazita, ML | marazita@pitt.edu | MARAZITA | | Hart, SP | | | | Sulima, PP | | | | Field, LL | | | | McHenry, TG | | | | Govil, M | | | | Cooper, ME | | | | Letra, A | | | | Menezes, R | | | | Narayanan, S | | | | Mansilla, MA | | | | Granjeiro, JM | | | | Vieira, AR | arv11@pitt.edu | ARV11 | | Lidral, AC | | | | Murray, JC | | | | Hart, TC | | | |
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Date: |
1 January 2009 |
Date Type: |
Publication |
Journal or Publication Title: |
European Journal of Human Genetics |
Volume: |
17 |
Number: |
6 |
Page Range: |
774 - 784 |
DOI or Unique Handle: |
10.1038/ejhg.2008.245 |
Schools and Programs: |
School of Dental Medicine > Dental Science |
Refereed: |
Yes |
ISSN: |
1018-4813 |
MeSH Headings: |
Alleles; Case-Control Studies; Cleft Lip--genetics; Cleft Palate--genetics; Genetic Predisposition to Disease; Humans; Lymphokines--genetics; Platelet-Derived Growth Factor--genetics; Polymorphism, Single Nucleotide--genetics; Promoter Regions, Genetic--genetics; Transcription, Genetic--genetics |
Other ID: |
NLM NIHMS94212, NLM PMC2788748 |
PubMed Central ID: |
PMC2788748 |
PubMed ID: |
19092777 |
Date Deposited: |
20 Sep 2012 20:12 |
Last Modified: |
22 Jun 2021 14:56 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/14319 |
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