Abstract
Prior to performance of linkage analysis, elimination of all Mendelian inconsistencies in the pedigree data is essential. Often, identification of erroneous genotypes by visual inspection can be very difficult and time consuming. In fact, sometimes the errors are not recognized until the stage of running linkage-analysis software. The effort then required to find the erroneous genotypes and to cross-reference pedigree and marker data that may have been recoded and renumbered can be not only tedious but also quite daunting, in the case of very large pedigrees. We have implemented four error-checking algorithms in a new computer program, PedCheck, which will assist researchers in identifying all Mendelian inconsistencies in pedigree data and will provide them with useful and detailed diagnostic information to help resolve the errors. Our program, which uses many of the algorithms implemented in VITESSE, handles large data sets quickly and efficiently, accepts a variety of input formats, and offers various error-checking algorithms that match the subtlety of the pedigree error. These algorithms range from simple parent-offspring-compatibility checks to a single-locus likelihood-based statistic that identifies and ranks the individuals most likely to be in error. We use various real data sets to illustrate the power and effectiveness of our program.
Full Text
The Full Text of this article is available as a PDF (495.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boehnke M., Cox N. J. Accurate inference of relationships in sib-pair linkage studies. Am J Hum Genet. 1997 Aug;61(2):423–429. doi: 10.1086/514862. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Göring H. H., Ott J. Relationship estimation in affected sib pair analysis of late-onset diseases. Eur J Hum Genet. 1997 Mar-Apr;5(2):69–77. [PubMed] [Google Scholar]
- Lange K., Goradia T. M. An algorithm for automatic genotype elimination. Am J Hum Genet. 1987 Mar;40(3):250–256. [PMC free article] [PubMed] [Google Scholar]
- Lange K., Weeks D. E. Efficient computation of lod scores: genotype elimination, genotype redefinition, and hybrid maximum likelihood algorithms. Ann Hum Genet. 1989 Jan;53(Pt 1):67–83. doi: 10.1111/j.1469-1809.1989.tb01122.x. [DOI] [PubMed] [Google Scholar]
- Lange K., Weeks D., Boehnke M. Programs for Pedigree Analysis: MENDEL, FISHER, and dGENE. Genet Epidemiol. 1988;5(6):471–472. doi: 10.1002/gepi.1370050611. [DOI] [PubMed] [Google Scholar]
- Lathrop G. M., Hooper A. B., Huntsman J. W., Ward R. H. Evaluating pedigree data. I. The estimation of pedigree error in the presence of marker mistyping. Am J Hum Genet. 1983 Mar;35(2):241–262. [PMC free article] [PubMed] [Google Scholar]
- Lathrop G. M., Huntsman J. W., Hooper A. B., Ward R. H. Evaluating pedigree data. II. Identifying the cause of error in families with inconsistencies. Hum Hered. 1983;33(6):377–389. doi: 10.1159/000153406. [DOI] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M., White R. L. Construction of human linkage maps: likelihood calculations for multilocus linkage analysis. Genet Epidemiol. 1986;3(1):39–52. doi: 10.1002/gepi.1370030105. [DOI] [PubMed] [Google Scholar]
- O'Connell J. R., Weeks D. E. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nat Genet. 1995 Dec;11(4):402–408. doi: 10.1038/ng1295-402. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]