Abstract
Rigorous analysis of human pedigree data is a vital concern in genetic epidemiology, human gene mapping, and genetic counseling. In this chapter we investigate efficient algorithms for likelihood computation on pedigree data, placing particular stress on the pioneering algorithm of Elston and Stewart [5]. It is no accident that their research coincided with the introduction of modern computing. To analyze human pedigree data is tedious, if not impossible, without computers. Pedigrees lack symmetry, and all simple closed-form solutions in mathematics depend on symmetry. The achievement of Elston and Stewart [5] was to recognize that closed-form solutions are less relevant than good algorithms. However, the Elston-Stewart algorithm is not the end of the story. Evaluation of pedigree likelihoods remains a subject sorely in need of further theoretical improvement. Linkage calculations alone are among the most demanding computational tasks in modern biology.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aslanidis C, Jansen G, Amemiya C, Shutler G, Mahadevan M, Tsilfidis C, Chen C, Alleman J, Wormskamp NGM, Vooijs M, Buxton J, Johnson K, Smeets HJM, Lennon GG, Carrano AV, Korneluk RG, Wieringa B, deJong PJ (1992) Cloning of the essential myotonic dystrophy region and mapping of the putative defect. Nature 355:548–551
Boehnke M (1991) Allele frequency estimation from data on relatives. Amer J Hum Genet 48:22–25
Dausset J, Cann H, Cohen D, Lathrop M, Lalouel J-M, White R (1990) Centre d’Etude du Polymorphisme Humain (CEPH): Collaborative genetic mapping of the human genome. Genomics 6:575–577
Dickson LE (1939) New First Course in the Theory of Equations. Wiley, New York
Elston RC, Stewart J (1971) A general model for the genetic analysis of pedigree data. Hum Hered 21:523–542
Goradia TM, Lange K, Miller PL, Nadkarni PM (1992) Fast computation of genetic likelihoods on human pedigree data. Hum Hered 42:42–62
Haidane JBS (1919) The combination of linkage values, and the calculation of distance between the loci of linked factors. J Genet 8:299–309
Hulbert-Shearon T, Boehnke M, Lange K (1995) Lod score curves for phase-unknown matings. Hum Hered 46:55–57
Kruglyak L, Daly MJ, Lander ES (1995) Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Amer J Hum Genet 56:519–527
Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996) Parametric and nonparametric linkage analysis: a unified multipoint approach. Amer J Hum Genet 58:1347–1363
Lander ES, Green P (1987) Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci USA 84:2363–2367
Lange K, Boehnke M (1983) Extensions to pedigree analysis. V. Optimal calculation of Mendelian likelihoods. Hum Hered 33:291–301
Lange K, Goradia TM (1987) An algorithm for automatic genotype elimination. Amer J Hum Genet 40:250–256
Lange K, Weeks D, Boehnke M (1988) Programs for pedigree analysis: MENDEL, FISHER, and dGENE. Genet Epidemiology 5:471–472
Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci 81:3443–3446
Lathrop GM, Lalouel J-M, White RL (1986) Construction of human linkage maps: Likelihood calculations for multilocus linkage analysis. Genet Epidemiology 3:39–52
Lewis M, Kaita H, Philipps S, Giblet E, Anderson JE, McAlpine PJ, Nickel B (1980) The position of the Radin blood group locus in relation to other chromosome 1 loci. Ann Hum Gent 44:179–184
Litt M, Kramer P, Browne D, Gancher S, Brunt ERP, Root D, Phromchotikul T, Dubay CJ, Nutt J (1994) A gene for Episodic Ataxia/Myokymia maps to chromosome 12pl3. Amer J Hum Genet 55:702–709
Murphy EA, Chase GA (1975) Principles of Genetic Counseling. Year Book Medical Publishers, Chicago
O’Connell JR, Weeks DE (1995) The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nature Genet 11:402–408
Ott J (1974) Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Amer J Hum Genet 26:588–597
Ott J (1991) Analysis of Human Genetic Linkage, revised ed. Johns Hopkins University Press, Baltimore
Terwilliger JD, Ott J (1994) Handbook of Human Genetic Linkage. Johns Hopkins University Press, Baltimore
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Lange, K. (1997). Computation of Mendelian Likelihoods. In: Mathematical and Statistical Methods for Genetic Analysis. Statistics for Biology and Health. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-2739-5_7
Download citation
DOI: https://doi.org/10.1007/978-1-4757-2739-5_7
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4757-2741-8
Online ISBN: 978-1-4757-2739-5
eBook Packages: Springer Book Archive