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Comparison of Requirements and Capabilities of Major Multipurpose Software Packages

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 850)

Abstract

The aim of this chapter is to introduce the reader to commonly used software packages and illustrate their input requirements, analysis options, strengths, and limitations. We focus on packages that perform more than one function and include a program for quality control, linkage, and association analyses. Additional inclusion criteria were (1) programs that are free to academic users and (2) currently supported, maintained, and developed. Using those criteria, we chose to review three programs: Statistical Analysis for Genetic Epidemiology (S.A.G.E.), PLINK, and Merlin. We will describe the required input format and analysis options. We will not go into detail about every possible program in the packages, but we will give an overview of the packages requirements and capabilities.

Key words

Software S.A.G.E Merlin PLINK Statistical analysis Linkage analysis Association analysis Quality control GUI Data management 
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References

  1. 1.
    Epstein MP, Duren WL, Boehnke M (2000) Improved inference of relationships for pairs of individuals. Am J Hum Genet 67: 1219–1231PubMedGoogle Scholar
  2. 2.
    Keen KJ, Elston RC (2003) Robust asymptotic sampling theory for correlations in pedigrees. Stat Med 22: 3229–3247PubMedCrossRefGoogle Scholar
  3. 3.
    Bonney GE (1984) On the statistical determination of major gene mechanisms in continuous human traits: regressive models. Am J Med Genet 18: 731–749PubMedCrossRefGoogle Scholar
  4. 4.
    George VT, Elston RC (1988) Generalized modulus power transformations. Commun Statist Theory Meth 17: 2933–2952CrossRefGoogle Scholar
  5. 5.
    Fernando RL, Stricker C, Elston RC (1994) The finite polygenic mixed model: an alternative formulation for the mixed model of inheritance. Theor Appl Genet 88: 573–580CrossRefGoogle Scholar
  6. 6.
    Lange K (1997) An approximate model of polygenic inheritance. Genetics 147: 1423–1430PubMedGoogle Scholar
  7. 7.
    Karunaratne PM, Elston RC (1998) A multivariate logistic model (MLM) for analyzing binary family data. Am J Med Genet 76: 428–437PubMedCrossRefGoogle Scholar
  8. 8.
    Elston RC, Stewart J (1971) A general model for the analysis of pedigree data. Hum Hered 21: 523–542PubMedCrossRefGoogle Scholar
  9. 9.
    Lander E, Green P (1987) Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci USA 84: 2363–2367PubMedCrossRefGoogle Scholar
  10. 10.
    Kruglyak L, Lander ES (1995) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57: 439–454PubMedGoogle Scholar
  11. 11.
    Sobel E, Lange K (1996) Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet 58: 1323–1337PubMedGoogle Scholar
  12. 12.
    Haseman J, Elston R (1972) The investigation of linkage between a quantitative trait and a marker locus. Behav Genet 2: 3–19PubMedCrossRefGoogle Scholar
  13. 13.
    Elston R, Buxbaum S, Jacobs K, Olson J (2000) Haseman and Elston revisited. Genet Epidemiol 19: 1–17PubMedCrossRefGoogle Scholar
  14. 14.
    Shete S, Jacobs K, Elston R (2003) Adding further power to the Haseman and Elston method for detecting linkage in larger sibships: weighting sums and differences. Hum Hered 55: 79–85PubMedCrossRefGoogle Scholar
  15. 15.
    Goddard KAB, Witte JS, Suarez BK, Catalona WJ, Olson JM (2001) Model-free linkage analysis with covariates confirms linkage of prostate cancer to chromosomes 1 and 4. Am J Hum Genet 68: 1197–1206PubMedCrossRefGoogle Scholar
  16. 16.
    Olson JM (1999) A general conditional-logistic model for affected-relative-pair linkage studies. Am J Hum Genet 65: 1760–1769PubMedCrossRefGoogle Scholar
  17. 17.
    Wang T, Elston RC (2005) Two-level Haseman-Elston regression for general pedigree data analysis. Genet Epidemiol 29: 12–22PubMedCrossRefGoogle Scholar
  18. 18.
    Wang T, Elston RC (2007) Regression-based multivariate linkage analysis with an application to blood pressure and body mass index. Ann Hum Genet 71: 96–106PubMedCrossRefGoogle Scholar
  19. 19.
    Laird NM, Horvath S, Xu X (2000) Implementing a unified approach to family-based tests of association. Genet Epidemiol 19, S36–S42PubMedCrossRefGoogle Scholar
  20. 20.
    Kopplin LJ, Igo RP Jr, Wang Y et al (2010) Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. Genes Immun 11: 609–621PubMedCrossRefGoogle Scholar
  21. 21.
    Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30: 97–101PubMedCrossRefGoogle Scholar
  22. 22.
    Markianos K, Daly MJ, Kruglyak L (2001) Efficient multipoint linkage analysis through reduction of inheritance space. Am J Hum Genet 68: 963–977PubMedCrossRefGoogle Scholar
  23. 23.
    Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81: 3443–3446PubMedCrossRefGoogle Scholar
  24. 24.
    Sobel E, Sengul H, Weeks DE (2001) Multipoint estimation of identity-by-descent probabilities at arbitrary positions among marker loci on general pedigrees. Hum Hered 52: 121–131PubMedCrossRefGoogle Scholar
  25. 25.
    Whittemore AS, Halpern J (1994) A class of tests for linkage using affected pedigree members. Biometrics 50: 118–127PubMedCrossRefGoogle Scholar
  26. 26.
    Sham PC, Purcell S, Cherny SS, Abecasis G (2002) Powerful regression-based quantitative-trait linkage analysis of general pedigrees. Am J Hum Genet 71: 238–253PubMedCrossRefGoogle Scholar
  27. 27.
    Kong A, Cox NJ (1997) Allele-sharing models: LOD scores and accurate linkage tests. Am J Hum Genet 61: 1179–1188PubMedCrossRefGoogle Scholar
  28. 28.
    Sham PC, Purcell S (2001) Equivalence between Haseman-Elston and variance-components linkage analyses for sib pairs. Am J Hum Genet 68: 1527–1532PubMedCrossRefGoogle Scholar
  29. 29.
    Chen W-M, Abecasis GR (2007) Family-based association tests for genomewide association scans. Am J Hum Genet 81: 913–926PubMedCrossRefGoogle Scholar
  30. 30.
    Zhang K, Zhao H (2006) A comparison of several methods for haplotype frequency estimation and haplotype reconstruction for tightly linked markers from general pedigrees. Genet Epidemiol 30: 423–437PubMedCrossRefGoogle Scholar
  31. 31.
    Li Y, Willer C, Sanna S, Abecasis GR (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10: 387–406PubMedCrossRefGoogle Scholar
  32. 32.
    Stephens M, Donnelly P (2003) A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73: 1162–1169PubMedCrossRefGoogle Scholar
  33. 33.
    Purcell S, Neale B, Todd-Brow K et al (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81: 559–575PubMedCrossRefGoogle Scholar
  34. 34.
    Milligan BG (2003) Maximum-likelihood estimation of relatedness. Genetics 163: 1153–1167PubMedGoogle Scholar
  35. 35.
    Spielman RS, Ewens WJ (1998) A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet 62: 450–458PubMedCrossRefGoogle Scholar
  36. 36.
    Abecasis GR, Cookson WO, Cardon LR (2000) Pedigree tests of transmission disequilibrium. Eur J Hum Genet 8: 545–551PubMedCrossRefGoogle Scholar
  37. 37.
    Nothnagel M, Ellinghaus D, Schreiber S, Krawczak M, Franke A (2009) A comprehensive evaluation of SNP genotype imputation. Hum Genet 125: 163–171PubMedCrossRefGoogle Scholar
  38. 38.
    Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62: 1198–1211PubMedCrossRefGoogle Scholar
  39. 39.
    Amos CI (1994) Robust variance-components approach for assessing genetic linkage in pedigrees. Am J Hum Genet 54: 535–543PubMedGoogle Scholar
  40. 40.
    Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996) Parametric and nonparametric linkage analysis, a unified multipoint approach. Am J Hum Genet 58: 1347–1363PubMedGoogle Scholar
  41. 41.
    Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21: 263–265PubMedCrossRefGoogle Scholar
  42. 42.
    Mukhopadhyay N, Almasy L, Schroeder M, Mulvihilll WP, Weeks DE (1999) Mega2, a data-handling program for facilitating genetic linkage and association analyses. Am J Hum Genet 65: A436Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Epidemiology and BiostatisticsCase Western Reserve UniversityClevelandUSA

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