Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2003 Jul;164(3):1161–1173. doi: 10.1093/genetics/164.3.1161

Genotyping error detection through tightly linked markers.

Guohua Zou 1, Deyun Pan 1, Hongyu Zhao 1
PMCID: PMC1462623  PMID: 12871922

Abstract

The identification of genotyping errors is an important issue in mapping complex disease genes. Although it is common practice to genotype multiple markers in a candidate region in genetic studies, the potential benefit of jointly analyzing multiple markers to detect genotyping errors has not been investigated. In this article, we discuss genotyping error detections for a set of tightly linked markers in nuclear families, and the objective is to identify families likely to have genotyping errors at one or more markers. We make use of the fact that recombination is a very unlikely event among these markers. We first show that, with family trios, no extra information can be gained by jointly analyzing markers if no phase information is available, and error detection rates are usually low if Mendelian consistency is used as the only standard for checking errors. However, for nuclear families with more than one child, error detection rates can be greatly increased with the consideration of more markers. Error detection rates also increase with the number of children in each family. Because families displaying Mendelian consistency may still have genotyping errors, we calculate the probability that a family displaying Mendelian consistency has correct genotypes. These probabilities can help identify families that, although showing Mendelian consistency, may have genotyping errors. In addition, we examine the benefit of available haplotype frequencies in the general population on genotyping error detections. We show that both error detection rates and the probability that an observed family displaying Mendelian consistency has correct genotypes can be greatly increased when such additional information is available.

Full Text

The Full Text of this article is available as a PDF (159.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akey J. M., Zhang K., Xiong M., Doris P., Jin L. The effect that genotyping errors have on the robustness of common linkage-disequilibrium measures. Am J Hum Genet. 2001 May 16;68(6):1447–1456. doi: 10.1086/320607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Douglas J. A., Boehnke M., Lange K. A multipoint method for detecting genotyping errors and mutations in sibling-pair linkage data. Am J Hum Genet. 2000 Mar 28;66(4):1287–1297. doi: 10.1086/302861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Douglas Julie A., Skol Andrew D., Boehnke Michael. Probability of detection of genotyping errors and mutations as inheritance inconsistencies in nuclear-family data. Am J Hum Genet. 2002 Jan 8;70(2):487–495. doi: 10.1086/338919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ehm M. G., Kimmel M., Cottingham R. W., Jr Error detection for genetic data, using likelihood methods. Am J Hum Genet. 1996 Jan;58(1):225–234. [PMC free article] [PubMed] [Google Scholar]
  5. Ehm M., Wagner M. A test statistic to detect errors in sib-pair relationships. Am J Hum Genet. 1998 Jan;62(1):181–188. doi: 10.1086/301668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldstein D. R., Zhao H., Speed T. P. The effects of genotyping errors and interference on estimation of genetic distance. Hum Hered. 1997 Mar-Apr;47(2):86–100. doi: 10.1159/000154396. [DOI] [PubMed] [Google Scholar]
  7. Gordon D., Heath S. C., Liu X., Ott J. A transmission/disequilibrium test that allows for genotyping errors in the analysis of single-nucleotide polymorphism data. Am J Hum Genet. 2001 Jul 5;69(2):371–380. doi: 10.1086/321981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gordon D., Leal S. M., Heath S. C., Ott J. An analytic solution to single nucleotide polymorphism error-detection rates in nuclear families: implications for study design. Pac Symp Biocomput. 2000:663–674. doi: 10.1142/9789814447331_0064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gordon D., Ott J. Assessment and management of single nucleotide polymorphism genotype errors in genetic association analysis. Pac Symp Biocomput. 2001:18–29. doi: 10.1142/9789814447362_0003. [DOI] [PubMed] [Google Scholar]
  10. Göring H. H., Terwilliger J. D. Linkage analysis in the presence of errors I: complex-valued recombination fractions and complex phenotypes. Am J Hum Genet. 2000 Mar;66(3):1095–1106. doi: 10.1086/302797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Göring H. H., Terwilliger J. D. Linkage analysis in the presence of errors II: marker-locus genotyping errors modeled with hypercomplex recombination fractions. Am J Hum Genet. 2000 Mar;66(3):1107–1118. doi: 10.1086/302798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Göring H. H., Terwilliger J. D. Linkage analysis in the presence of errors III: marker loci and their map as nuisance parameters. Am J Hum Genet. 2000 Mar 23;66(4):1298–1309. doi: 10.1086/302846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Göring H. H., Terwilliger J. D. Linkage analysis in the presence of errors IV: joint pseudomarker analysis of linkage and/or linkage disequilibrium on a mixture of pedigrees and singletons when the mode of inheritance cannot be accurately specified. Am J Hum Genet. 2000 Mar 23;66(4):1310–1327. doi: 10.1086/302845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lincoln S. E., Lander E. S. Systematic detection of errors in genetic linkage data. Genomics. 1992 Nov;14(3):604–610. doi: 10.1016/s0888-7543(05)80158-2. [DOI] [PubMed] [Google Scholar]
  15. O'Connell J. R., Weeks D. E. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998 Jul;63(1):259–266. doi: 10.1086/301904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ott J. Detecting marker inconsistencies in human gene mapping. Hum Hered. 1993 Jan-Feb;43(1):25–30. doi: 10.1159/000154109. [DOI] [PubMed] [Google Scholar]
  17. Shields D. C., Collins A., Buetow K. H., Morton N. E. Error filtration, interference, and the human linkage map. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6501–6505. doi: 10.1073/pnas.88.15.6501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sobel Eric, Papp Jeanette C., Lange Kenneth. Detection and integration of genotyping errors in statistical genetics. Am J Hum Genet. 2002 Jan 8;70(2):496–508. doi: 10.1086/338920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stringham H. M., Boehnke M. Identifying marker typing incompatibilities in linkage analysis. Am J Hum Genet. 1996 Oct;59(4):946–950. [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES