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Original Paper

Linkage Disequilibrium Mapping of Quantitative Trait Loci under Truncation Selection

Xiong M.a · Fan R.b · Jin L.c

Author affiliations

aHuman Genetics Center, University of Texas-Houston, Houston, Tex., bDepartment of Statistics, Texas A&M University, College Station, Tex., cDepartment of Envrinomental Health, University of Cincinnati, Cincinnati, Ohio, USA

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Hum Hered 2002;53:158–172

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 08, 2001
Accepted: April 01, 2002
Published online: June 11, 2009
Issue release date: July 2002

Number of Print Pages: 15
Number of Figures: 8
Number of Tables: 2

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: https://www.karger.com/HHE

Abstract

As a dense map of single nucleotide polymorphism (SNP) markers are available, population-based linkage disequilibrium (LD) mapping or association study is becoming one of the major tools for identifying quantitative trait loci (QTL) and for fine gene mapping. However, in many cases, LD between the marker and trait locus is not very strong. Approaches that maximize the potential of detecting LD will be essential for the success of LD mapping of QTL. In this paper, we propose two strategies for increasing the probability of detecting LD: (1) phenotypic selection and (2) haplotype LD mapping. To provide the foundations for LD mapping of QTL under selection, we develop analytic tools for assessing the impact of phenotypic selection on allele and haplotype frequencies, and LD under three trait models: single trait locus, two unlinked trait loci, and two linked trait loci with or without epistasis. In addition to a traditional χ2 test, which compares the difference in allele or haplotype frequencies in the selected sample and population sample, we present multiple regression methods for LD mapping of QTL, and investigate which methods are effective in employing phenotypic selection for QTL mapping. We also develop a statistical framework for investigating and comparing the power of the single marker and multilocus haplotype test for LD mapping of QTL. Finally, the proposed methods are applied to mapping QTL influencing variation in systolic blood pressure in an isolated Chinese population.

© 2002 S. Karger AG, Basel


References

  1. Altshuler D, Daly M, Kruglyak L: Guilt by association. Nat Genet 2000;26:135–137.
  2. Amos CI, Elston RC, Wilson AF, Bailey-Wilson JE: A more powerful robust sib-pair test of linkage for quantitative traits. Genet Epidemiol 1989;6:435–449.
  3. Andronico G, Mangano MT, Ferrara L, Lamanna D, Mule G, Cerasola G: Insulin-like growth factor 1 and pressure load in hypertensive patients. Am J Hypertension 1996;6:607–609.
    External Resources
  4. Blangero J, Almasy L: Multipoint oligogenic linkage analysis of quantitative traits. Genet Epidemiol 1997;14:959–964.
  5. Blangero J, Williams JT, Almasy L: Quantitative trait locus mapping using human pedigrees. Hum Biol 2000;72:35–62.
  6. Bovenhuis H, Spelman RJ: Selective genotyping to detect quantitative trait loci for multiple traits in outbred populations. J Dairy Sci 2000;83:173–180.
  7. Bulmer MG: The Mathematical Theory of Quantitative Genetics. Oxford, Clarendon Press, 1980.
  8. Chakravarti A: Single nucleotide polymorphisms to a future of genetic medicine. Nature 2001;409:822–823.
  9. Cheverud JM, Routman EJ: Epistasis as a source of increased additive genetic variance at population bottlenecks. Evolution 1996;50:1042–1051.
  10. Collins FS, Ginger MS, Chaakravarti A: Variations of a theme: Cataloging human DNA sequence variation. Science 1997;278:1580–1581.
  11. Devlin B, Roeder K, Bacanu S-A: Unbiased methods for population-based association studies. Genet Epidemiol 2001;21:273–284.
  12. Ewens WJ: Mathematical Population Genetics. New York, Springer, 1979.
  13. Falconer DS, Mackay TFC: Introduction to quantitative genetics, ed 4. London, Longman, 1996, pp 15–19.
  14. Gray IC, Cambell DA, Spurr NK: Single nucleotide polymorphisms as tools in human genetics. Hum Mol Genet 2000;9:2403–2408.
    External Resources
  15. Graybill FA: Theory and Application of the Linear Model. Pacific Grove, Wadsworth & Brooks/Cole Advanced Books & Software, 1976.
  16. Hartl DL, Clark AG: Principles of Population Genetics, ed 2. Sunderland, Sinauer, 1989.
  17. Haseman JK, Elston RC: The investigation of linkage between a quantitative trait and a marker locus. Behav Genet 1972;2:3–19.
  18. Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, Hara M, Hinokio Y, Lindner TH, Mashima H, Schwarz PE, del Bosque-Plata L, Horikawa Y, Oda Y, Yoshiuchi I, Colilla S, Polonsky KS, Wei S, Concannon P, Iwasaki N, Schulze J, Baier LJ, Bogardus C, Groop L, Boerwinkle E, Hanis CL, Bell GI: Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000;26:163–175.
  19. The International SNP Map Working Group: A map of human genome, 2001.
  20. Jiang J, Akey JM, Shi J, Yiong MM, Wang Y, Shen Y, Yu X, Chen H, Wu H, Xiao J, Lu D, Huang W, Jin L: Association of blood pressure and polymorphisms in the promoter region of catalase in a Chinese population. Hum Genet 2001;109:95–98.
    External Resources
  21. Kaplan N, Morris R: Issues concerning association studies for fine mapping a susceptibility gene for a complex disease. Genet Epidemiol 2001;20:432–457.
  22. Lynch M, Walsh B: Genetics and Analysis of Quantitative Traits. Sunderland, Sinauer, 1998.
  23. Morita H, Kurihara H, Kurihara Y, Kuwaki T, Shindo T, Oh-hashi Y, Kumada M, Yazaki Y: Responses of blood pressure and catecholamine metabolism to high salt loading in endothelin-1 knockout mice. Hypertens Res 1999;22:11–16.
  24. Narain P: Statistical Genetics. New York, Wiley, 1990.
  25. Ohno Y, Tanase H, Nabika T, Otsuka K, Sesaki T, Suzawa T, Morri T, Yamori Y, Saruta T: Selective genotyping with epistasis can be utilized for a major quantitative trait loci mapping in hypertension in rats. Genetics 2000;155:785–792.
    External Resources
  26. Risch NJ: Searching for genetic determinants in the new millennium. Nature 2000;405:847–856.
  27. Risch N, Merikangas K: The future of genetic studies of complex human diseases. Science 1996;273:1516–1617.
  28. Rosmond R, Ukkola O, Chagnon M, Bouchard C, Bjorntorp P: Polymorphisms of the beta2-adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men. J Intern Med 2000;248:239–244.
    External Resources
  29. Schork NJ: Extended multipoint identity-by-descent analysis of human quantitative traits: Efficiency, power, and modeling considerations. Am J Hum Genet 1993;53:1306–1319.
  30. Slatkin M: Disequilibrium mapping of a quantitative-trait locus in an expanding population. Am J Hum Genet 1999;64:1765–1773.
    External Resources
  31. Spielman RS, McGinnis RE, Ewens WJ: Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993;52:506–561.
  32. Turelli M, Barton NH: Genetic and statistical analyses of strong selection on polygenic traits: What, me normal? Genetics 1994;138:913–941.
    External Resources
  33. Wang DG, Fan JB, Siao CJ, Berno A, Yong P, Sapolsky R, Ghandour G, Perkins N, Winchester E, Spencer J, et al: Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 1998;280:1077–1082.
  34. Van Gestel S, Houwing-Duistermaat JJ, Adolfsson R, van Duijn C, van Broeckhoven C: Power of selective genotyping in genetic association of quantitative traits. Behav Genet 2000;30:141–146.
    External Resources
  35. Weiss KM, Terwilliger JD: How many diseases does it take to map a gene with SNPs. Nat Genet 2000;26:151–157.
  36. Wu CI, Palopoli MF: Genetics of postmating reproductive isolation in animals. Annu Rev Genet 1994;28:283–308.
  37. Xiong MM, Jin L, Boerwinkle E: Linkage disequilibrium based regression: A method for mapping quantitative trait loci in humans. Am J Hum Genet 1998;63:A45.
  38. Zhao J, Li W, Xiong MM: Population based linkage disequilibrium mapping of QTL: An application to simulated data in an isolated population. Genet Epidemiol 2001;21(suppl 1):S655–S659.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 08, 2001
Accepted: April 01, 2002
Published online: June 11, 2009
Issue release date: July 2002

Number of Print Pages: 15
Number of Figures: 8
Number of Tables: 2

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: https://www.karger.com/HHE


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