Title:
METHODS OF DNA MARKER-BASED GENETIC ANALYSIS USING ESTIMATED HAPLOTYPE FREQUENCIES AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO2001091026
Kind Code:
A3
Abstract:
The present invention is primarily drawn to methods of DNA marker-based genetic analysis using estimated haplotype frequencies to draw inferences about the relationship between haplotypes and traits or diseases. Unlike many haplotype analysis methods that require phase information that can be difficult to obtain from samples of non-haploid species, the instant methods are based on strategies for estimating haplotype frequencies from unphased diploid genotype data using the Estimation-Maximization (E-M) algorithm to overcome the missing phase information. These estimated haplotype frequencies can then be used in a variety of statistical analyses, including those to infer the existence of a disease gene. The process can include: 1) estimating haplotype frequencies; 2) computing test statistics; and 3) drawing inferences.
Inventors:
SCHORK NICHOLAS (US)
FALLIN DANI (US)
LISSARRAGUE SEBASTIEN (FR)
FALLIN DANI (US)
LISSARRAGUE SEBASTIEN (FR)
Application Number:
PCT/IB2001/001284
Publication Date:
March 13, 2003
Filing Date:
May 22, 2001
Export Citation:
Assignee:
GENSET SA (FR)
SCHORK NICHOLAS (US)
FALLIN DANI (US)
LISSARRAGUE SEBASTIEN (FR)
SCHORK NICHOLAS (US)
FALLIN DANI (US)
LISSARRAGUE SEBASTIEN (FR)
International Classes:
G01N33/50; G16B40/00; G01N33/48; G06F19/00; G16B20/40; G16B30/00; (IPC1-7): G06F19/00
Domestic Patent References:
| WO1999052942A2 | 1999-10-21 |
Other References:
FALLIN D SCHORK N J: "Accuracy of haplotype frequency estimation for biallelic loci, via the expectation-maximization algorithm for unphased diploid genotype data", AMERICAN JOURNAL OF HUMAN GENETICS, AMERICAN SOCIETY OF HUMAN GENETICS, CHICAGO, IL, US, vol. 67, no. 4, 22 August 2000 (2000-08-22), pages 947 - 959, XP002953525, ISSN: 0002-9297
LONG A D AND LANGLEY C H: "The Power of Association Studies to Detect the Contribution of Candidate Genetic Loci to Variation in Complex Traits", GENOME RESEARCH, vol. 9, no. 8, August 1999 (1999-08-01), pages 720 - 731, XP002222375, Retrieved from the Internet [retrieved on 20021121]
EXCOFFIER L ET AL: "MAXIMUM-LIKELIHOOD ESTIMATION OF MOLECULAR HAPLOTYPE FREQUENCIES IN A DIPLOID POPULATION", MOLECULAR BIOLOGY AND EVOLUTION, THE UNIVERSITY OF CHICAGO PRESS, US, vol. 12, 1995, pages 921 - 927, XP000891487, ISSN: 0737-4038
LONG J C ET AL: "AN E-M ALGORITHM AND TESTING STRATEGY FOR MULTIPLE-LOCUS HAPLOTYPES", AMERICAN JOURNAL OF HUMAN GENETICS, UNIVERSITY OF CHICAGO PRESS, CHICAGO,, US, vol. 56, 1995, pages 799 - 810, XP002944464, ISSN: 0002-9297
NIELSEN D M EHM M G WEIR B S: "Detecting marker-disease association by testing for Hardy-Weinberg disequilibrium at a marker locus", AMERICAN JOURNAL OF HUMAN GENETICS, UNIVERSITY OF CHICAGO PRESS, CHICAGO,, US, vol. 63, 1999, pages 1531 - 1540, XP002953526, ISSN: 0002-9297
HAWLEY M E ET AL: "HAPLO: A PROGRAM USING THE EM ALGORITHM TO ESTIMATE THE FREQUENCIESOF MULTI-SITE HAPLOTYPES", JOURNAL OF HEREDITY, OXFORD UNIVERSITY PRESS, CARY, GB, vol. 86, no. 5, 1995, pages 409 - 411, XP000891489, ISSN: 0022-1503
LONG A D AND LANGLEY C H: "The Power of Association Studies to Detect the Contribution of Candidate Genetic Loci to Variation in Complex Traits", GENOME RESEARCH, vol. 9, no. 8, August 1999 (1999-08-01), pages 720 - 731, XP002222375, Retrieved from the Internet
EXCOFFIER L ET AL: "MAXIMUM-LIKELIHOOD ESTIMATION OF MOLECULAR HAPLOTYPE FREQUENCIES IN A DIPLOID POPULATION", MOLECULAR BIOLOGY AND EVOLUTION, THE UNIVERSITY OF CHICAGO PRESS, US, vol. 12, 1995, pages 921 - 927, XP000891487, ISSN: 0737-4038
LONG J C ET AL: "AN E-M ALGORITHM AND TESTING STRATEGY FOR MULTIPLE-LOCUS HAPLOTYPES", AMERICAN JOURNAL OF HUMAN GENETICS, UNIVERSITY OF CHICAGO PRESS, CHICAGO,, US, vol. 56, 1995, pages 799 - 810, XP002944464, ISSN: 0002-9297
NIELSEN D M EHM M G WEIR B S: "Detecting marker-disease association by testing for Hardy-Weinberg disequilibrium at a marker locus", AMERICAN JOURNAL OF HUMAN GENETICS, UNIVERSITY OF CHICAGO PRESS, CHICAGO,, US, vol. 63, 1999, pages 1531 - 1540, XP002953526, ISSN: 0002-9297
HAWLEY M E ET AL: "HAPLO: A PROGRAM USING THE EM ALGORITHM TO ESTIMATE THE FREQUENCIESOF MULTI-SITE HAPLOTYPES", JOURNAL OF HEREDITY, OXFORD UNIVERSITY PRESS, CARY, GB, vol. 86, no. 5, 1995, pages 409 - 411, XP000891489, ISSN: 0022-1503
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