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