Abstract
Linkage analysis is used to map genetic loci using observations on relatives. It can be applied to both major gene disorders (parametric linkage) and complex diseases (model-free or non-parametric linkage), and it can be based on either a relatively small number of microsatellite markers or a denser map of single nucleotide polymorphisms (SNPs). We describe the methods commonly used to map loci influencing disease susceptibility or a quantitative trait. Application of these methods to simulated but realistic datasets is illustrated in some detail using the program Merlin. We provide some guidance on the best methods to use in different situations and on the interpretation of output.
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References
Abecasis, G. R., Cherny, S. S., Cookson, W. O., and Cardon, L. R. (2002) Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nature Genetics 30, 97–101.
Ott, J. (1999) Analysis of Human Genetic Linkage, Second ed. The Johns Hopkins University Press, Baltimore, MD.
Teare, M. D., and Barrett, J. H. (2005) Genetic epidemiology 2 – Genetic linkage studies. Lancet 366, 1036–1044.
Chiano, M. N., and Yates, J. R. W. (1995) Linkage detection under heterogeneity and the mixture problem. Annals of Human Genetics 59, 83–95.
Lander, E., and Kruglyak, L. (1995) Genetic dissection of complex traits – guidelines for interpreting and reporting linkage results. Nature Genetics 11, 241–247.
Cannings, C., and Thompson, E. A. (1981) Genealogical and Genetic Structure. Cambridge University Press, Cambridge.
Lathrop, G. M., and Lalouel, J. M. (1984) Easy calculations of lod scores and genetic risks on small computers. American Journal of Human Genetics 36, 460–465.
Cottingham, R. W., Idury, R. M., and Schaffer, A. A. (1993) Faster sequential genetic-linkage computations. American Journal of Human Genetics 53, 252–263.
Kruglyak, L., Daly, M. J., ReeveDaly, M. P., and Lander, E. S. (1996) Parametric and nonparametric linkage analysis: a unified multipoint approach. American Journal of Human Genetics 58, 1347–1363.
Gudbjartsson, D. F., Jonasson, K., Frigge, M. L., and Kong, A. (2000) Allegro, a new computer program for multipoint linkage analysis. Nature Genetics 25, 12–13.
Wijsman, E. M., Rothstein, J. H., and Thompson, E. A. (2006) Multipoint linkage analysis with many multiallelic or dense diallelic markers: Markov chain-Monte Carlo provides practical approaches for genome scans on general pedigrees. American Journal of Human Genetics 79, 846–858.
Almasy, L., and Blangero, J. (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. American Journal of Human Genetics 62, 1198–1211.
The BHF Family Heart Study Research Group (2005) A genomewide linkage study of 1933 families affected by premature coronary artery disease: The British Heart Foundation (BHF) family heart study. American Journal of Human Genetics 77, 1011–1020.
Wigginton, J. E., and Abecasis, G. R. (2005) PEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data. Bioinformatics 21, 3445–3447.
Whittemore, A. S., and Halpern, J. (1994) A class of tests for linkage using affected pedigree members. Biometrics 50, 118–127.
Kong, A., and Cox, N. J. (1997) Allele-sharing models: LOD scores and accurate linkage tests. American Journal of Human Genetics 61, 1179–1188.
Roberts, S. B., MacLean, C. J., Neale, M. C., Eaves, L. J., and Kendler, K. S. (1999) Replication of linkage studies of complex traits: an examination of variation in location estimates. American Journal of Human Genetics 65, 876–884.
Haseman, J. K., and Elston, R. C. (1972) Investigation of linkage between a quantitative trait and a marker locus. Behavior Genetics 2, 3–19.
Sham, P. C., Purcell, S., Cherny, S. S., and Abecasis, G. R. (2002) Powerful regression-based quantitative-trait linkage analysis of general pedigrees. American Journal of Human Genetics 71, 238–253.
Schaid, D. J., Guenther, J. C., Christensen, G. B. et al (2004) Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility loci. American Journal of Human Genetics 75, 948–965.
Huang, Q., Shete, S., and Amos, C. I (2004) Ignoring linkage disequilibrium among tight linked markers induces false-positive evidence of linkage for affected sib pair analysis. American Journal of Human Genetics 75, 1106–1112.
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Barrett, J.H., Teare, M.D. (2011). Linkage Analysis. In: Yu, B., Hinchcliffe, M. (eds) In Silico Tools for Gene Discovery. Methods in Molecular Biology, vol 760. Humana Press. https://doi.org/10.1007/978-1-61779-176-5_2
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DOI: https://doi.org/10.1007/978-1-61779-176-5_2
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