Hum Hered 2002;54:99–110

Enhanced Pedigree Error Detection

Sun L.a,d · Wilder K.a,b · McPeek M.S.a,c
Departments of aStatistics, bMathematics, and cHuman Genetics, University of Chicago, Chicago, Ill., USA; dPresent affiiliation: Department of Public Health Sciences, University of Toronto, and Hospital for Sick Children, Toronto, Canada
email Corresponding Author

 goto top of outline Key Words

  • Markov chain
  • Hidden Markov model
  • Likelihood ratio test
  • Pedigree error
  • Misspecified relationship
  • Relationship estimation
  • Software

 goto top of outline Abstract

Accurate information on the relationships among individuals in a study is critical for valid linkage analysis. We extend the MLLR, EIBD, AIBS and IBS tests for detection of misspecified relationships to a broader range of relative pairs, and we improve the two-stage screening procedure for analyzing large data sets. We have developed software, PREST, which calculates the test statistics and performs the corresponding hypothesis tests for relationship misclassification in general outbred pedigrees. When a potential pedigree error is detected, our companion program, ALTERTEST, can be used to determine which relationships are compatible with the genotype data. Both programs are now freely available on the web.

Copyright © 2003 S. Karger AG, Basel

 goto top of outline References
  1. McPeek MS, Sun L: Statistical tests for detection of misspecified relationships by use of genome-screen data. Am J Hum Genet 2000;66:1076–1094.
  2. Chakraborty R, Jin L: Determination of relatedness between individuals using DNA fingerprinting. Hum Biol 1993a;65:875–895.
  3. Stringham HM, Boehnke M: Identifying marker typing incompatibilities in linkage analysis. Am J Hum Genet 1996;59:946–950.
  4. Göring HHH, Ott J: Relationship estimation in affected sib pair analysis of late-onset diseases. Eur J Hum Genet 1997;5:69–77.
  5. Boehnke M, Cox NJ: Accurate inference of relationships in sib-pair linkage studies. Am J Hum Genet 1997;61:423–429.
  6. Ehm MG, Wagner M: A test statistic to detect errors in sib-pair relationships. Am J Hum Genet 1998;62:181–188.
  7. Broman KW, Weber JL: Estimation of pairwise relationships in the presence of genotyping errors. Am J Hum Genet 1998;63:1563–1564.
  8. O’Connell JR, Weeks DE: PedCheck: A program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998;63:259–266.
  9. Olson JM: Relationship estimation by Markov-process models in a sib-pair linkage study. Am J Hum Genet 1999;64:1464–1472.
  10. Epstein MP, Duren WL, Boehnke M: Improved relationship inference for pairs of individuals. Am J Hum Genet 2000;67:1219–1231.
  11. Sun L, Abney M, McPeek MS: Detection of misspecified relationships in inbred and outbred pedigrees. Genet Epidemiol 2001;21:S36–S41.

    External Resources

  12. Abney M, McPeek MS, Ober C: Estimation of variance components of quantitative traits in inbred populations. Am J Hum Genet 2000;66:629–650.
  13. Donnelly KP: The probability that related individuals share some section of genome identical by descent. Theor Pop Biol 1983;23:34–63.
  14. Feingold E: Markov processes for modeling and analyzing a new genetic mapping method. J Appl Prob 1993;30:766–779.
  15. McPeek MS: Inference on pedigree structure from genome screen data. Statistica Sinica 2002;12:311–335.
  16. Thompson EA: The estimation of pairwise relationships. Ann Hum Genet 1975;39:173–188.
  17. Broman KW, Murray JC, Sheffield VC, White RL, Weber JL: Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet 1998;63:861–869.
  18. Lin SL, Speed TP: Incorporating crossover interference into pedigree analysis using the chi2 model. Hum Hered 1996;46:315–322.
  19. Browning S: Relationship information contained in gamete identity by descent data. J Comp Biol 1998;5:323–334.
  20. Zhao H, Liang F: On relationship inference using gamete identity by descent data. J Comp Biol 2001;8:191–200.
  21. Sieberts SK, Wijsman EM, Thompson EA: Relationship inference from trios of individuals, in the presence of typing error. Am J Hum Genet 2002;70:170–180.

 goto top of outline Author Contacts

Lei Sun
Department of Public Health Sciences, University of Toronto
12 Queen’s Park Crescent West
Toronto, ON M5S 1A8 (Canada)
Tel. +1 416 978 7519, Fax +1 416 978 8299, E-Mail

 goto top of outline Article Information

Received: Received: December 12, 2001
Revision received: October 4, 2002
Accepted: October 7, 2002
Number of Figures : 1, Number of Tables : 6, Number of References : 21

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965–1983)

Vol. 54, No. 2, Year 2002 (Cover Date: Released January 2002)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information:

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.