Journal Mobile Options
Table of Contents
Vol. 65, No. 4, 2008
Issue release date: January 2008
Section title: Original Paper
Free Access
Hum Hered 2008;65:199–208

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

Li B. · Leal S.M.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Tex., USA
email Corresponding Author

Dr. Suzanne M. Leal

Baylor College of Medicine, Department of Molecular and Human Genetics

One Baylor Plaza, Alkek Building N1619.01

Houston, TX 77030 (USA)

Tel. +1 713 798 4001, Fax +1 713 798 5741, E-Mail


  1. Huang Q, Shete S, Amos CI: Ignoring linkage disequilibrium among tightly linked markers induces false-positive evidence of linkage for affected sib pair analysis. Am J Hum Genet 2004;75:1106–1112.
  2. Weber JL, Broman KW: Genotyping for human whole-genome scans: Past, present, and future. Adv Genet 2001;42:77–96.
  3. Murray SS, Oliphant A, Shen R, McBride C, Steeke RJ, Shannon SG, Rubano T, Kermani BG, Fan JB, Chee MS, Hansen MS: A highly informative snp linkage panel for human genetic studies. Nat Methods 2004;1:113–117.
  4. Kennedy GC, Matsuzaki H, Dong S, Liu WM, Huang J, Liu G, Su X, Cao M, Chen W, Zhang J, Liu W, Yang G, Di X, Ryder T, He Z, Surti U, Phillips MS, Boyce-Jacino MT, Fodor SP, Jones KW: Large-scale genotyping of complex DNA. Nat Biotechnol 2003;21:1233–1237.
  5. Wilcox MA, Pugh EW, Zhang H, Zhong X, Levinson DF, Kennedy GC, Wijsman EM: Comparison of single-nucleotide polymorphisms and microsatellite markers for linkage analysis in the coga and simulated data sets for genetic analysis workshop 14:Presentation groups 1, 2, and 3. Genet Epidemiol 2005;29(suppl 1):S7–S28.
  6. Cottingham RW Jr, Idury RM, Schaffer AA: Faster sequential genetic linkage computations. Am J Hum Genet 1993;53:252–263.
  7. Abecasis GR, Cherny SS, Cookson WO, Cardon LR: Merlin – rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002;30:97–101.
  8. Abecasis GR, Wigginton JE: Handling marker-marker linkage disequilibrium: Pedigree analysis with clustered markers. Am J Hum Genet 2005;77:754–767.
  9. Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, P. D, Consortium IH: A haplotype map of the human genome. Nature 2005;437:1299–1320.
  10. Gudbjartsson DF, Thorvaldsson T, Kong A, Gunnarsson G, Ingolfsdottir A: Allegro version 2. Nat Genet 2005;37:1015–1016.
  11. Gudbjartsson DF, Jonasson K, Frigge ML, Kong A: Allegro, a new computer program for multipoint linkage analysis. Nat Genet 2000;25:12–13.
  12. Sobel E, Lange K: Descent graphs in pedigree analysis: Applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet 1996;58:1323–1337.
  13. Weeks DE, Sobel E, O’Connell JR, Lange K: Computer programs for multilocus haplotyping of general pedigrees. Am J Hum Genet 1995;56:1506–1507.
  14. Freimer NB, Sandkuijl LA, Blower SM: Incorrect specification of marker allele frequencies: Effects on linkage analysis. Am J Hum Genet 1993;52:1102–1110.
  15. Knapp M, Seuchter SA, Baur MP: The effect of misspecifying allele frequencies in incompletely typed families. Genet Epidemiol 1993;10:413–418.
  16. Huang Q, Shete S, Swartz M, Amos CI: Examining the effect of linkage disequilibrium on multipoint linkage analysis. BMC Genet 2005;6 Suppl 1:S83.
  17. Schaid DJ, McDonnell SK, Wang L, Cunningham JM, Thibodeau SN: Caution on pedigree haplotype inference with software that assumes linkage equilibrium. Am J Hum Genet 2002;71:992–995.
  18. Boyles AL, Scott WK, Martin ER, Schmidt S, Li YJ, Ashley-Koch A, Bass MP, Schmidt M, Pericak-Vance MA, Speer MC, Hauser ER: Linkage disequilibrium inflates type i error rates in multipoint linkage analysis when parental genotypes are missing. Hum Hered 2005;59:220–227.
  19. Van Camp G, Smith RJH: Hereditary hearing loss homepage: Http://webhost.Ua.Ac. Be/hhh/. 2007.
  20. Leal SM, Yan K, Muller-Myhsok B: Simped: A simulation program to generate haplotype and genotype data for pedigree structures. Hum Hered 2005;60:119–122.
  21. Ott J: Linkage analysis and family classification under heterogeneity. Ann Hum Genet 1983;47:311–320.
  22. Goddard KA, Wijsman EM: Characteristics of genetic markers and maps for cost-effective genome screens using diallelic markers. Genet Epidemiol 2002;22:205–220.
  23. Leutenegger AL, Prum B, Genin E, Verny C, Lemainque A, Clerget-Darpoux F, Thompson EA: Estimation of the inbreeding coefficient through use of genomic data. Am J Hum Genet 2003;73:516–523.
  24. Genin E, Clerget-Darpoux F: Consanguinity and the sib-pair method: An approach using identity by descent between and within individuals. Am J Hum Genet 1996;59:1149–1162.
  25. Leutenegger AL, Genin E, Thompson EA, Clerget-Darpoux F: Impact of parental relationships in maximum lod score affected sib-pair method. Genet Epidemiol 2002;23:413–425.
  26. Liu F, Elefante S, van Duijn CM, Aulchenko YS: Ignoring distant genealogic loops leads to false-positives in homozygosity mapping. Ann Hum Genet 2006;70:965–970.
  27. Miano MG, Jacobson SG, Carothers A, Hanson I, Teague P, Lovell J, Cideciyan AV, Haider N, Stone EM, Sheffield VC, Wright AF: Pitfalls in homozygosity mapping. Am J Hum Genet 2000;67:1348–1351.