Maternal transmission effects of the PAX genes among cleft case-parent trios from four populations

Jae Woong Sull, Kung Yee Liang, Jacqueline B. Hetmanski, Daniele Daniele Fallin, Roxanne G. Ingersoll, Jiwan Park, Yah Huei Wu-Chou, Philip K. Chen, Samuel S. Chong, Felicia Cheah, Vincent Yeow, Beyoung Yun Park, Sun Ha Jee, Ethylin W. Jabs, Richard Redett, Alan F Scott, Terri L Beaty

Research output: Contribution to journalArticle

Abstract

Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of 1 in 700 live births. The paired box (PAX) genes have been suggested as candidate genes for CL/ P based largely on mouse models; however, few human studies have focused on this gene family. This study tests for association between markers in four PAX genes and CL/P using a case-parent trio design considering parent-of-origin effects. Trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 34 single nucleotide polymorphisms (SNPs) in the PAX3, PAX6, PAX7, and PAX9 genes. We performed the transmission disequilibrium test (TDT) on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test (TAT) and the parent-of-origin likelihood ratio test (PO-LRT). TDT analysis showed one SNP (rs766325) in PAX7 yielding evidence of linkage and association when parent-of-origin was not considered, with an OR(transmission)=1.62 (P=0.003), and five SNPs in PAX6 (including two pairs in near perfect linkage disequilibrium). TAT analysis of all trios revealed two SNPs in PAX7 and four SNPs in PAX3 showing significant excess maternal transmission. For these six SNPs, the maternal OR(transmission) ranged between 1.74 and 2.40, and PO-LRT was also significant (P-values=0.035-0.012). When this analysis was limited to trios with male cases, SNPs in PAX7 showed higher maternal OR(transmission) and greater significance. PAX genes may influence the risk of CL/P through maternal effects, possibly imprinting, which seems to be stronger among male cases.

Original languageEnglish (US)
Pages (from-to)831-839
Number of pages9
JournalEuropean Journal of Human Genetics
Volume17
Issue number6
DOIs
StatePublished - 2009

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Single Nucleotide Polymorphism
Population
Genes
Cleft Palate
Mothers
Maternal Inheritance
Cleft Lip
Singapore
Linkage Disequilibrium
Live Birth
Korea
Taiwan

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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Maternal transmission effects of the PAX genes among cleft case-parent trios from four populations. / Sull, Jae Woong; Liang, Kung Yee; Hetmanski, Jacqueline B.; Fallin, Daniele Daniele; Ingersoll, Roxanne G.; Park, Jiwan; Wu-Chou, Yah Huei; Chen, Philip K.; Chong, Samuel S.; Cheah, Felicia; Yeow, Vincent; Park, Beyoung Yun; Jee, Sun Ha; Jabs, Ethylin W.; Redett, Richard; Scott, Alan F; Beaty, Terri L.

In: European Journal of Human Genetics, Vol. 17, No. 6, 2009, p. 831-839.

Research output: Contribution to journalArticle

Sull, JW, Liang, KY, Hetmanski, JB, Fallin, DD, Ingersoll, RG, Park, J, Wu-Chou, YH, Chen, PK, Chong, SS, Cheah, F, Yeow, V, Park, BY, Jee, SH, Jabs, EW, Redett, R, Scott, AF & Beaty, TL 2009, 'Maternal transmission effects of the PAX genes among cleft case-parent trios from four populations', European Journal of Human Genetics, vol. 17, no. 6, pp. 831-839. https://doi.org/10.1038/ejhg.2008.250
Sull, Jae Woong ; Liang, Kung Yee ; Hetmanski, Jacqueline B. ; Fallin, Daniele Daniele ; Ingersoll, Roxanne G. ; Park, Jiwan ; Wu-Chou, Yah Huei ; Chen, Philip K. ; Chong, Samuel S. ; Cheah, Felicia ; Yeow, Vincent ; Park, Beyoung Yun ; Jee, Sun Ha ; Jabs, Ethylin W. ; Redett, Richard ; Scott, Alan F ; Beaty, Terri L. / Maternal transmission effects of the PAX genes among cleft case-parent trios from four populations. In: European Journal of Human Genetics. 2009 ; Vol. 17, No. 6. pp. 831-839.
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abstract = "Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of 1 in 700 live births. The paired box (PAX) genes have been suggested as candidate genes for CL/ P based largely on mouse models; however, few human studies have focused on this gene family. This study tests for association between markers in four PAX genes and CL/P using a case-parent trio design considering parent-of-origin effects. Trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 34 single nucleotide polymorphisms (SNPs) in the PAX3, PAX6, PAX7, and PAX9 genes. We performed the transmission disequilibrium test (TDT) on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test (TAT) and the parent-of-origin likelihood ratio test (PO-LRT). TDT analysis showed one SNP (rs766325) in PAX7 yielding evidence of linkage and association when parent-of-origin was not considered, with an OR(transmission)=1.62 (P=0.003), and five SNPs in PAX6 (including two pairs in near perfect linkage disequilibrium). TAT analysis of all trios revealed two SNPs in PAX7 and four SNPs in PAX3 showing significant excess maternal transmission. For these six SNPs, the maternal OR(transmission) ranged between 1.74 and 2.40, and PO-LRT was also significant (P-values=0.035-0.012). When this analysis was limited to trios with male cases, SNPs in PAX7 showed higher maternal OR(transmission) and greater significance. PAX genes may influence the risk of CL/P through maternal effects, possibly imprinting, which seems to be stronger among male cases.",
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AU - Hetmanski, Jacqueline B.

AU - Fallin, Daniele Daniele

AU - Ingersoll, Roxanne G.

AU - Park, Jiwan

AU - Wu-Chou, Yah Huei

AU - Chen, Philip K.

AU - Chong, Samuel S.

AU - Cheah, Felicia

AU - Yeow, Vincent

AU - Park, Beyoung Yun

AU - Jee, Sun Ha

AU - Jabs, Ethylin W.

AU - Redett, Richard

AU - Scott, Alan F

AU - Beaty, Terri L

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