To investigate the association between the TGFA:c.3851T > C (rs11466285) and TGFA:c.3822G > A (rs3771523) single-nucleotide polymorphisms (SNPs) and nonsyndromic cleft lip and/or cleft palate (CL/P) with microarray in north China.
Design and Setting
Test association by both case-control and case-parent analysis.
Subjects and Methods
Two SNPs of 150 controls, 166 cases, and 271 of their parents were genotyped using microarray based on the allele-specific primer extension, and chi-square statistics and family-based association test analyses were performed.
Results
Both sequencing and microarray analysis produced identical results. We found significant evidence of overtransmission of the C allele of c.3851 T > C and the A allele of C.3822G > A in case-parent trios for CL/P but not for cleft palate only (CP). Significant differences for both genotypic and allelic distributions between cases and controls were found at C.3822G > A and c.3851 T > C for CL/P but not for CP. The TGFA [C; G] and [T; A] haplotypes showed significant overtransmission.
Conclusions
These results support that two SNPs are associated with nonsyndromic CL/P but not for CP in northern Chinese populations. It was demonstrated that this microarray is suitable to test SNPs associated with nonsyndromic CL/P.
ArdingerH.H., BuetowK.H., BellG.I., BardachJ., VanDemarkD.R., MurrayJ.C.Association of genetic variation of the transforming growth factor-alpha gene with cleft lip and palate. Am J Hum Genet.1989; 5: 348–353.
2.
BassB.L., WeintraubH.An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell.1988; 55: 1089–1098.
3.
BeatyT.H., HetmanskiJ.B., FallinM.D., ParkJ.W., SullJ.W., McIntoshI., LiangK.Y., VanderkolkC.A., RedettR.J., BoyadjievS.A.Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations. Hum Genet.2006; 120: 501–518.
4.
DixonM.J., FergusonM.W.The effects of epidermal growth factor, transforming growth factor α and β and platelet derived growth factor on murine palatal shelves in organ culture. Arch Oral Biol.1992; 37: 395–410.
5.
DixonM.J., GarnerJ., FergusonM.W.J.Immunolocalization of epidermal growth factor (EGF), EGF receptor and transforming growth factor alpha (TGFa) during murine palatogenesis in vivo and in vitro. Anat Embryol (Berl).1991; 84: 83–91.
6.
ErdoganF., KirchnerR., MannW., RopersH.H., NuberU.A.Detection of mitochondrial single nucleotide polymorphisms using a primer elongation reaction on oligonucleotide microarrays. Nucleic Acids Res.2001; 29(7): E3.
7.
HirschhornJ.N., SklarP., Lindblad-TohK.. SBE-TAGS: an array-based method for efficient single-nucleotide polymorphism genotyping. Proc Natl Acad Sci U S A.2000; 97: 12164–12169.
8.
IamaroonA., TaitB., DiewertV.M.Cell proliferation and expression of EGF, TGF-a, and EGF receptor in the developing primary palate. J Dent Res.1996; 75: 1534–1539.
MachidaJ., SatoF., KaetsuA., NishiokaM., AmanoM., YamamotoT., NatsumeN.Candidate genes for nonsyndromic cleft lip and palate [abstract]. J Craniomaxillofac Surg.2000; 28(suppl): 50s.
13.
MachidaJ., YoshiuraK., FunkhauserC.D., NatsumeN., KawaiT., MurrayJ.C.Transforming growth factor-alpha (TGFA): genomic structure, boundary sequences, and mutation analysis in nonsyndromic cleft lip/palate and cleft palate only. Genomics.1999; 61: 237–242.
14.
MarazitaM.L., FieldL.L., CooperM.E., TobiasR., MaherB.S., PeanchitlertkajornS., LiuY.E.Nonsyndromic cleft lip with or without cleft palate in China: assessment of candidate regions. Cleft Palate Craniofac J.2002; 39: 149–156.
15.
MarçanoA.C., DoudneyK., BraybrookC.. TBX22 mutations are a frequent cause of cleft palate. J Med Genet.2004; 41: 68–74.
16.
MiettinenP.J., ChinJ.R., ShumL., SlavkinH.C., ShulerC.F., DerynckR., WerbZ.Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure. Nat Genet.1999; 22: 69–73.
PastinenT., KurgA., MetspaluA., PeltonenL., SyvänenA.C.Minisequencing: a specific tool for DNA analysis and diagnostics on oligonucleotide arrays. Genome Res.1997; 7: 606–614.
19.
ShenY., ChengL., WanW.D., LuZ.D., LiaoL.M., CuiY.G., LiuJ.Y.Association of some SNP in TGFA, IRF6 and nonsyndromic cleft lip with or without cleft palate by DNA microarray teachnology. Chin J Lab Med.2007; 30: 1349–1353.
20.
ShiangR., LidralA.C., ArdingerH.H., BuetowK.H., RomittiP.A., MungerR.G., MurrayJ.C.Association of transforming growth-factor alpha gene polymorphisms with nonsyndromic cleft palate only (CPO). Am J Hum Genet.1993; 53: 836–843.
21.
van den BoogaardM.J., DorlandM.Beemer FA, van Amstel HK. MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans. Nat Genet.2000; 24: 342–343.
22.
VieiraA.R.Association between the transforming growth factor alpha gene and nonsyndromic oral clefts: a HuGE review. Am J Epidemiol.2006; 163: 790–810.
23.
VieiraA.R., AvilaJ.R., Daack-HirschS.. Medical sequencing of candidate genes for nonsyndromic cleft lip and palate. PLoS Genet.2005; 1: e64.
24.
WagnerR.W., SmithJ.E., CoopermanB.S., NishikuraK.A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc Natl Acad Sci U S A.1989; 86: 2647–2651.
25.
WillingM.C., PruchnoC.J., AtkinsonM., ByersP.H.Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen. Am J Hum Genet.1992; 51: 508–515.
26.
ZeigerJ.S., BeatyT.H., LiangK.Y.Oral clefts, maternal smoking, and TGFA: a meta-analysis of gene-environment interaction. Cleft Palate Craniofac J.2005; 42: 58–63.
