Maternal transmission effect of a PDGF-C SNP on nonsyndromic cleft lip with or without palate from a Chinese population

PLoS One. 2012;7(9):e46477. doi: 10.1371/journal.pone.0046477. Epub 2012 Sep 28.

Abstract

Cleft lip with or without palate (CL/P) is a common congenital anomaly with a high birth prevalence in China. Based on a previous linkage signal of nonsyndromic CL/P (NSCL/P) on the chromosomal region 4q31-q32 from the Chinese populations, we screened the 4q31-q32 region for susceptibility genes in 214 trios of Han Chinese. PDGF-C, an important developmental factor, resides in the region and has been implicated in NSCL/P. However, in our family-based association test (transmission disequilibrium test; TDT), we could not conclude an association between PDGF-C and NSCL/P as previously suggested. Instead, we found strong evidence for parent-of-origin effect at a PDGF-C SNP, rs17035464, by a likelihood ratio test (unadjusted p-value = 0.0018; I(m) = 2.46). The location of rs17035464 is 13 kb downstream of a previously reported, NSCL/P-associated SNP, rs28999109. Furthermore, a patient from our sample trios was observed with a maternal segmental uniparental isodisomy (UPD) in a region containing rs17035464. Our findings support the involvement of PDGF-C in the development of oral clefts; moreover, the UPD case report contributes to the collective knowledge of rare variants in the human genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • China
  • Cleft Lip / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lymphokines / genetics*
  • Male
  • Microsatellite Repeats
  • Pedigree
  • Platelet-Derived Growth Factor / genetics*
  • Polymorphism, Single Nucleotide*
  • Uniparental Disomy

Substances

  • Lymphokines
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor C

Grants and funding

This work was supported by Doctoral Program Foundation of Institutions of Higher Education of China (200800230021), Beijing Municipal Natural Science Foundation (7092087), National Basic Research Program of China (Grant No.2007CB511901) and 100 Talents Program of the Chinese Academy of Sciences to DMW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.