TY - JOUR
T1 - Maternal Transmission Effect of a PDGF-C SNP on Nonsyndromic Cleft Lip with or without Palate from a Chinese Population
AU - Wu, Di
AU - Wang, Mei
AU - Wang, Xingang
AU - Yin, Ningbei
AU - Song, Tao
AU - Li, Haidong
AU - Zhang, Feng
AU - Zhang, Yongbiao
AU - Ye, Zhenqing
AU - Yu, Jun
AU - Wang, Duen Mei
AU - Zhao, Zhenmin
PY - 2012/9/28
Y1 - 2012/9/28
N2 - 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; Im = 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.
AB - 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; Im = 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.
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U2 - 10.1371/journal.pone.0046477
DO - 10.1371/journal.pone.0046477
M3 - Article
C2 - 23029525
AN - SCOPUS:84866992452
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 9
M1 - e46477
ER -