Maternal Transmission Effect of a <em>PDGF-C</em> SNP on Nonsyndromic Cleft Lip with or without Palate from a Chinese Population

<div><p>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. <em>PDGF-C</em>, 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 <em>PDGF-C</em> and NSCL/P as previously suggested. Instead, we found strong evidence for parent-of-origin effect at a <em>PDGF-C</em> SNP, rs17035464, by a likelihood ratio test (unadjusted p-value = 0.0018; <em>I_m</em> = 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 <em>PDGF-C</em> in the development of oral clefts; moreover, the UPD case report contributes to the collective knowledge of rare variants in the human genome.</p> </div

Schematic diagram of two-step mapping strategy.

<p>The genotyping was first conducted with 10 STR markers covering a 30-Mb region on 4q31–q32 and followed by 80 SNPs spanning the region from D4S1498 to D4S413. Lastly, the minimal UPD region was estimated to be from rs17035464 to D4S1498 in a physical distance of 14 Kb.</p

Description of sample in two-step genotyping.

<p>Description of sample in two-step genotyping.</p

Linkage disequilibrium (LD) pattern of the 80 SNPs in step 2.

<p>Linkage disequilibrium derived from the parents of our sample set as measured in <i>r</i>². White, <i>r</i>² = 0; Shades of gray, 0<<i>r</i>²<1; Black, <i>r</i>² = 1.</p