Human Genetics

, Volume 120, Issue 4, pp 501–518

Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations

  • T. H. Beaty
  • J. B. Hetmanski
  • M. D. Fallin
  • J. W. Park
  • J. W. Sull
  • I. McIntosh
  • K. Y. Liang
  • C. A. VanderKolk
  • R. J. Redett
  • S. A. Boyadjiev
  • E. W. Jabs
  • S. S. Chong
  • F. S. H. Cheah
  • Y. H. Wu-Chou
  • P. K. Chen
  • Y. F. Chiu
  • V. Yeow
  • I. S. L. Ng
  • J. Cheng
  • S. Huang
  • X. Ye
  • H. Wang
  • R. Ingersoll
  • A. F. Scott
Original Investigation

DOI: 10.1007/s00439-006-0235-9

Cite this article as:
Beaty, T.H., Hetmanski, J.B., Fallin, M.D. et al. Hum Genet (2006) 120: 501. doi:10.1007/s00439-006-0235-9

Abstract

Isolated oral clefts, including cleft lip with/without cleft palate (CL/P) and cleft palate (CP), have a complex and heterogeneous etiology. Case-parent trios from three populations were used to study genes spanning chromosome 2, where single nucleotide polymorphic (SNP) markers were analyzed individually and as haplotypes. Case-parent trios from three populations (74 from Maryland, 64 from Singapore and 95 from Taiwan) were genotyped for 962 SNPs in 104 genes on chromosome 2, including two well-recognized candidate genes: TGFA and SATB2. Individual SNPs and haplotypes (in sliding windows of 2–5 SNPs) were used to test for linkage and disequilibrium separately in CL/P and CP trios. A novel candidate gene (ZNF533) showed consistent evidence of linkage and disequilibrium in all three populations for both CL/P and CP. SNPs in key regions of ZNF533 showed considerable variability in estimated genotypic odds ratios and their significance, suggesting allelic heterogeneity. Haplotype frequencies for regions of ZNF533 were estimated and used to partition genetic variance into among-and within-population components. Wright’s fixation index, a measure of genetic diversity, showed little difference between Singapore and Taiwan compared with Maryland. The tensin-1 gene (TNS1) also showed evidence of linkage and disequilibrium among both CL/P and CP trios in all three populations, albeit at a lower level of significance. Additional genes (VAX2, GLI2, ZHFX1B on 2p; WNT6–WNT10A and COL4A3–COL4A4 on 2q) showed consistent evidence of linkage and disequilibrium only among CL/P trios in all three populations, and TGFA showed significant evidence in two of three populations.

Supplementary material

439_2006_235_MOESM1_ESM.xls (428 kb)
Supplementary material 1
439_2006_235_MOESM2_ESM.ppt (924 kb)
Supplementary material 2

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • T. H. Beaty
    • 1
  • J. B. Hetmanski
    • 1
  • M. D. Fallin
    • 1
  • J. W. Park
    • 1
  • J. W. Sull
    • 1
  • I. McIntosh
    • 2
    • 3
  • K. Y. Liang
    • 1
    • 7
  • C. A. VanderKolk
    • 4
  • R. J. Redett
    • 4
  • S. A. Boyadjiev
    • 2
  • E. W. Jabs
    • 2
  • S. S. Chong
    • 5
  • F. S. H. Cheah
    • 5
  • Y. H. Wu-Chou
    • 6
  • P. K. Chen
    • 6
  • Y. F. Chiu
    • 7
  • V. Yeow
    • 8
  • I. S. L. Ng
    • 8
  • J. Cheng
    • 8
  • S. Huang
    • 9
  • X. Ye
    • 10
  • H. Wang
    • 11
  • R. Ingersoll
    • 2
  • A. F. Scott
    • 2
  1. 1.Johns Hopkins UniversityBaltimoreUSA
  2. 2.Institute of Genetic MedicineJohns Hopkins UniversityBaltimoreUSA
  3. 3.American University of the CaribbeanSt. MaartenNetherlands Antilles
  4. 4.School of MedicineJohns Hopkins UniversityBaltimoreUSA
  5. 5.Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  6. 6.Chang Gung Memorial HospitalTaipeiTaiwan
  7. 7.National Health Research InstituteTaipeiTaiwan
  8. 8.KK Women’s and Children’s HospitalSingaporeSingapore
  9. 9.Chinese Academy of Medical SciencesBeijingPeople’s Republic of China
  10. 10.WuHan UniversityWuHanPeople’s Republic of China
  11. 11.Peking University Health Science CenterBeijingPeople’s Republic of China