Abstract
There is currently great interest in the genetics community in identifying the genes that are involved in complex (multifactorial) diseases. One standard approach uses family-based ”linkage” methods to identify regions of the genome that harbor susceptibility genes, and then population-based ”linkage-disequilibrium” (LD) methods to search more narrowly for the culprit genes. Many of the important statistical issues involved in the first phase of this process, linkage mapping, have been addressed, but data analysis for LD-mapping remains extremely challenging. In this article we describe our work on developing a full statistical framework for LD mapping based on a population genetics model known as the coalescent.
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
Abecasis, G.R., Cherny, S.S., Cookson, W.O., Cardon, L.R.: Merlin–rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97–101 (2002)
Abney, M., Ober, C., McPeek, M.S.: Quantitative-trait homozygosity and association mapping and empirical genomewide significance in large, complex pedigrees: fasting serum-insulin level in the Hutterites. Am. J. Hum. Genet. 70, 920–934 (2002)
Fearnhead, P., Donnelly, P.: Estimating recombination rates from population genetic data. Genetics 159, 1299–1318 (2001)
Griffiths, R.C., Marjoram, P.: Ancestral inference from samples of DNA sequences with recombination. J. Comp. Biol. 3, 479–502 (1996)
Hastbacka, J., delaChapelle, A., Kaitila, I., Sistonen, P., Weaver, A., Lander, E.: Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat. Genet. 2, 204–211 (1992)
Horikawa, Y., Oda, N., Cox, N., Li, X., Orho-Melander, M., Hara, M., Hinokio, Y., Lindner, T.H., Mashima, H., Schwarz, P.E., del Bosque-Plata, L., Horikawa, Y., Oda, Y., Yoshiuchi, I., Colilla, S., Polonsky, K.S., Wei, S., Concannon, P., Iwasaki, N., Schulze, J., Baier, L.J., Bogardus, C., Groop, L., Boerwinkle, E., Hanis, C.L., Bell, G.I.: Genetic variation in the gene encoding calpain-10 is associated with Type 2 Diabetes Mellitus. Nat. Genet. 26, 163–175 (2000)
Hudson, R.: Gene genealogies and the coalescent process. In: Futuyma, D., Antonovics, J. (eds.) Oxford surveys in evolutionary biology, vol. 7, pp. 1–44. Oxford University Press, Oxford (1990)
Kerem, B.-S., Rommens, J., Buchanan, J.M., Markiewicz, J.A., Cox, T.K., Chakravarti, A., Buchwald, M.: Identification of the cystic fibrosis gene: Genetic analysis. Science 245, 1073–1080 (1989)
Kruglyak, L., Daly, M.J., Reeve-Daly, M.P., Lander, E.S.: Parametric and non-parametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363 (1996)
Kuhner, M.K., Yamato, J., Felsenstein, J.: Maximum likelihood estimation of recombination rates from population data. Genetics 156, 1393–1401 (2000)
Lazzeroni, L.C.: Empirical linkage-disequilibrium mapping. Am. J. Hum. Gen. 62, 159–170 (1997)
Liu, J.S., Sabatti, C., Teng, J., Keats, B.J., Risch, N.: Bayesian analysis of haplotypes for linkage disequilibrium mapping. Genome Res. 11, 1716–1724 (2001)
McPeek, M.S., Strahs, A.: Assessment of linkage disequilibrium by the decay of haplotype sharing, with application to fine-scale genetic mapping. Am. J. Hum. Genet. 65, 858–875 (1999)
Morris, A.P., Whittaker, J.C., Balding, D.J.: Bayesian fine-scale mapping of disease loci, by hidden Markov models. Am. J. Hum. Genet. 67, 155–169 (2000)
Morris, A.P., Whittaker, J.C., Balding, D.J.: Fine-scale mapping of disease loci via shattered coalescent modeling of genealogies. Am. J. Hum. Genet. 70, 686–707 (2002)
Nielsen, R.: Estimation of population parameters and recombination rates from single nucleotide polymorphisms. Genetics 154, 931–942 (2000)
Nordborg, M.: Coalescent theory. In: Balding, D., Bishop, M., Cannings, C. (eds.) Handbook of statistical genetics, pp. 179–212. Wiley, Chichester (2001)
Risch, N.: Searching for genetic determinants in the new millennium. Nature 405, 847–856 (2000)
Spielman, R.S., McGinnis, R.E., Ewens, W.J.: Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506–513 (1993)
Stephens, M., Smith, N.J., Donnelly, P.: A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68, 978–989 (2001)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Zöllner, S., Pritchard, J.K. (2004). A Coalescent-Based Approach for Complex Disease Mapping. In: Istrail, S., Waterman, M., Clark, A. (eds) Computational Methods for SNPs and Haplotype Inference. RSNPsH 2002. Lecture Notes in Computer Science(), vol 2983. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-24719-7_10
Download citation
DOI: https://doi.org/10.1007/978-3-540-24719-7_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-21249-2
Online ISBN: 978-3-540-24719-7
eBook Packages: Springer Book Archive