Excess maternal transmission of markers in TCOF1 among cleft palate case-parent trios from three populations.
Isolated cleft palate is among the most common human birth defects. The TCOF1 gene has been suggested as a candidate gene for cleft palate based on animal models. This study tests for association between markers in TCOF1 and isolated, nonsyndromic cleft palate using a case-parent trio design considering parent-of-origin effects. Case-parent trios from three populations (comprising a total of 81 case-parent trios) were genotyped for single nucleotide polymorphisms (SNPs) in the TCOF1 gene. We used the transmission disequilibrium test and the transmission asymmetry test on individual SNPs. When all trios were combined, the odds ratio for transmission of the minor allele, OR(transmission), was significant for SNP rs15251 (OR = 2.88, P = 0.007), as well as rs2255796 and rs2569062 (OR = 2.08, P = 0.03; OR = 2.43, P = 0.041; respectively) when parent of origin was not considered. The transmission asymmetry test also revealed one SNP (rs15251) showing excess maternal transmission significant at the P = 0.005 level (OR = 6.50). Parent-of-origin effects were assessed using the parent-of-origin likelihood ratio test on both SNPs and haplotypes. While the parent-of-origin likelihood ratio test was only marginally significant for this SNP (P = 0.136), analysis of haplotypes of rs2255796 and rs15251 suggested excess maternal transmission. Therefore, these data suggest TCOF1 may influence risk of cleft palate through a parent-of-origin effect.
Sull
Jae Woong
JW
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Liang
Kung-Yee
KY
Hetmanski
Jacqueline B
JB
Fallin
M Daniele
MD
Ingersoll
Roxanne G
RG
Park
Ji Wan
JW
Wu-Chou
Yah-Huei
YH
Chen
Philip K
PK
Chong
Samuel S
SS
Cheah
Felicia
F
Yeow
Vincent
V
Park
Beyoung Yun
BY
Jee
Sun Ha
SH
Jabs
Ethylin W
EW
Redett
Richard
R
Scott
Alan F
AF
Beaty
Terri H
TH
D016009:Chi-Square Distribution; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D018392:Genomic Imprinting; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008297:Male; D008396:Maryland / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D013624:Taiwan / Q000453:epidemiology
D005819:Genetic Markers; D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human