title: Maternal transmission effect of a PDGF-C SNP on nonsyndromic cleft lip with or without palate from a Chinese population.
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.
authors.affiliation: Department of Cleft Lip and Palate, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Xingang
authors.initials: X
authors.lastname: Wang
authors.forename: Ningbei
authors.initials: N
authors.lastname: Yin
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Haidong
authors.initials: H
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Yongbiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Duen-Mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D002681:China; D002971:Cleft Lip / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy
chemical_list: D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C411423:platelet-derived growth factor C