Molecular Biology and Evolution, Vol 12, 921-927, Copyright © 1995 by Society for Molecular Biology and Evolution
L Excoffier and M Slatkin
Molecular techniques allow the survey of a large number of linked
polymorphic loci in random samples from diploid populations. However, the
gametic phase of haplotypes is usually unknown when diploid individuals are
heterozygous at more than one locus. To overcome this difficulty, we
implement an expectation-maximization (EM) algorithm leading to
maximum-likelihood estimates of molecular haplotype frequencies under the
assumption of Hardy-Weinberg proportions. The performance of the algorithm
is evaluated for simulated data representing both DNA sequences and highly
polymorphic loci with different levels of recombination. As expected, the
EM algorithm is found to perform best for large samples, regardless of
recombination rates among loci. To ensure finding the global maximum
likelihood estimate, the EM algorithm should be started from several
initial conditions. The present approach appears to be useful for the
analysis of nuclear DNA sequences or highly variable loci. Although the
algorithm, in principle, can accommodate an arbitrary number of loci, there
are practical limitations because the computing time grows exponentially
with the number of polymorphic loci. Although the algorithm, in principle,
can accommodate an arbitrary number of loci, there are practical
limitations because the computing time grows exponentially with the number
of polymorphic loci.
ORIGINAL ARTICLE
Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population
Department of Anthropology, University of Geneva, Switzerland.
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Y.-L. Lo, J.-C. Yu, S.-T. Chen, G.-C. Hsu, Y.-C. Mau, S.-L. Yang, P.-E. Wu, and C.-Y. Shen Breast cancer risk associated with genotypic polymorphism of the mitotic checkpoint genes: a multigenic study on cancer susceptibility Carcinogenesis, May 1, 2007; 28(5): 1079 - 1086. [Abstract] [Full Text] [PDF]
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M. J. Gunter, R. B. Hayes, N. Chatterjee, M. Yeager, R. Welch, R. E. Schoen, L. Yakochi, A. Schatzkin, and U. Peters Insulin Resistance-Related Genes and Advanced Left-Sided Colorectal Adenoma Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 703 - 708. [Abstract] [Full Text] [PDF]
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M. L. Slattery, K. Curtin, R. Baumgartner, C. Sweeney, T. Byers, A. R. Giuliano, K. B. Baumgartner, and R. R. Wolff IL6, Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Breast Cancer Risk in Women Living in the Southwestern United States Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 747 - 755. [Abstract] [Full Text] [PDF]
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L. Wang, S. K. McDonnell, J. P. Slusser, S. J. Hebbring, J. M. Cunningham, S. J. Jacobsen, J. R. Cerhan, M. L. Blute, D. J. Schaid, and S. N. Thibodeau Two Common Chromosome 8q24 Variants Are Associated with Increased Risk for Prostate Cancer Cancer Res., April 1, 2007; 67(7): 2944 - 2950. [Abstract] [Full Text] [PDF]
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Q. Lan, T. Zheng, S. Chanock, Y. Zhang, M. Shen, S. S. Wang, S. I. Berndt, S. H. Zahm, T. R. Holford, B. Leaderer, et al. Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma Carcinogenesis, April 1, 2007; 28(4): 823 - 827. [Abstract] [Full Text] [PDF]
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A. Tanabe, T. Yanagiya, A. Iida, S. Saito, A. Sekine, A. Takahashi, T. Nakamura, T. Tsunoda, S. Kamohara, Y. Nakata, et al. Functional Single-Nucleotide Polymorphisms in the Secretogranin III (SCG3) Gene that Form Secretory Granules with Appetite-Related Neuropeptides Are Associated with Obesity J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1145 - 1154. [Abstract] [Full Text] [PDF]
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E. L. Goode, J. D. Potter, W. R. Bamlet, D. N. Rider, and J. Bigler Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps Carcinogenesis, February 1, 2007; 28(2): 328 - 341. [Abstract] [Full Text] [PDF]
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R. Kimura, K. Kamino, M. Yamamoto, A. Nuripa, T. Kida, H. Kazui, R. Hashimoto, T. Tanaka, T. Kudo, H. Yamagata, et al. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between {beta}-amyloid production and tau phosphorylation in Alzheimer disease Hum. Mol. Genet., January 1, 2007; 16(1): 15 - 23. [Abstract] [Full Text] [PDF]
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P. Paschou, M. W. Mahoney, A. Javed, J. R. Kidd, A. J. Pakstis, S. Gu, K. K. Kidd, and P. Drineas Intra- and interpopulation genotype reconstruction from tagging SNPs Genome Res., January 1, 2007; 17(1): 96 - 107. [Abstract] [Full Text] [PDF]
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B. Voetsch, R. C. Jin, C. Bierl, K. S. Benke, G. Kenet, P. Simioni, F. Ottaviano, B. P. Damasceno, J. M. Annichino-Bizacchi, D. E. Handy, et al. Promoter Polymorphisms in the Plasma Glutathione Peroxidase (GPx-3) Gene: A Novel Risk Factor for Arterial Ischemic Stroke Among Young Adults and Children Stroke, January 1, 2007; 38(1): 41 - 49. [Abstract] [Full Text] [PDF]
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X. Chen, X. Wang, S. Hossain, F. A. O'Neill, D. Walsh, L. Pless, K. V. Chowdari, V. L. Nimgaonkar, S. G. Schwab, D. B. Wildenauer, et al. Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia Hum. Mol. Genet., November 15, 2006; 15(22): 3329 - 3342. [Abstract] [Full Text] [PDF]
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S. I. Berndt, E. A. Platz, M. D. Fallin, L. W. Thuita, S. C. Hoffman, and K. J. Helzlsouer Genetic Variation in the Nucleotide Excision Repair Pathway and Colorectal Cancer Risk. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2263 - 2269. [Abstract] [Full Text] [PDF]
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S. S. Wang, J. R. Cerhan, P. Hartge, S. Davis, W. Cozen, R. K. Severson, N. Chatterjee, M. Yeager, S. J. Chanock, and N. Rothman Common Genetic Variants in Proinflammatory and Other Immunoregulatory Genes and Risk for Non-Hodgkin Lymphoma Cancer Res., October 1, 2006; 66(19): 9771 - 9780. [Abstract] [Full Text] [PDF]
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M. M. Gaudet, S. Chanock, J. Lissowska, S. I. Berndt, B. Peplonska, L. A. Brinton, R. Welch, M. Yeager, A. Bardin-Mikolajczak, and M. Garcia-Closas Comprehensive Assessment of Genetic Variation of Catechol-O-Methyltransferase and Breast Cancer Risk Cancer Res., October 1, 2006; 66(19): 9781 - 9785. [Abstract] [Full Text] [PDF]
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C.-H. Hsieh, K.-H. Liang, Y.-J. Hung, L.-C. Huang, D. Pei, Y.-T. Liao, S.-W. Kuo, M. S.-J. Bey, J.-L. Chen, and E. Y. Chen Analysis of epistasis for diabetic nephropathy among type 2 diabetic patients Hum. Mol. Genet., September 15, 2006; 15(18): 2701 - 2708. [Abstract] [Full Text] [PDF]
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P.-Y. Liu, Y. Lu, and H.-W. Deng Accurate Haplotype Inference for Multiple Linked Single-Nucleotide Polymorphisms Using Sibship Data Genetics, September 1, 2006; 174(1): 499 - 509. [Abstract] [Full Text] [PDF]
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L B Hughes, T M Beasley, H Patel, H K Tiwari, S L Morgan, J E Baggott, K G Saag, J McNicholl, L W Moreland, G S Alarcon, et al. Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis Ann Rheum Dis, September 1, 2006; 65(9): 1213 - 1218. [Abstract] [Full Text] [PDF]
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R. J. Hung, P. Boffetta, F. Canzian, N. Moullan, N. Szeszenia-Dabrowska, D. Zaridze, J. Lissowska, P. Rudnai, E. Fabianova, D. Mates, et al. Sequence Variants in Cell Cycle Control Pathway, X-ray Exposure, and Lung Cancer Risk: A Multicenter Case-Control Study in Central Europe Cancer Res., August 15, 2006; 66(16): 8280 - 8286. [Abstract] [Full Text] [PDF]
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P Rahman, F Siannis, C Butt, V Farewell, L Peddle, F Pellett, and D Gladman TNF{alpha} polymorphisms and risk of psoriatic arthritis Ann Rheum Dis, July 1, 2006; 65(7): 919 - 923. [Abstract] [Full Text] [PDF]
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