An extension of, and comments on, Example 13.

Recent references on marker-assisted introgressions (pages 407--413)

• Behringer, R. 1998. Supersonic congenics? Nature Genetics 18: 108.
• Hill, W. G. 1993. Variation in genetic composition in backcrossing programs. Journal of Heredity 84: 212-213.
• Hospital, Chevalet, and Mulsant. 1992. Using markers in gene introgression programs. Genetics 132: 1199-1210.
• Hospital and Charcosset. 1997. Marker-assisted introgression of quantitative trait loci. Genetics 147: 1469-1485.
• Markel et al. 1997. Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains. Nature Genetics 17: 280-284.
• Visscher, Haley, and Thompson. 1996. Marker assisted introgression in backcross breeding programs. Genetics 144: 1923-1932.
• Wakeland et. al. 1997. Speed congenics: a classic technique in the fast lane (relative speaking). Immunology Today 18: 472-477.
• Weil et al. 1997. Genotype selection to rapidly breed congenic strains. Genetics 146: 1061-1069.

Background: While the TDT is presented in the book (pages 420-422) as an approach for detecting linkage of a major QTL to a very tightly-linked marker that controls for the effects of population stratification (see Example 17, Chapter 14), it is now appreciated that it often has more power than allele-sharing methods (such as ASP, etc., see Chapter 16, pp. 525- 533) for detecting linkage to tightly-linked markers.

• That the TDT can have greater power than allele-sharing methods is discussed by:
  • Risch and Merikangas (1996 Science 273: 1516-17; 1997 Science 275: 1329-1330)
• Extensions of the TDT to allow for multiple alleles are given by:
  • Spielman and Ewens (1996 American J. Human Genetics 59: 983-989)
  • Schaid (1996 Genet Epidemiology 13: 423-450)
• Further power studies are given by:
  • Kaplan et al (1996 American J. Human Genetics 60: 691--702)
• The standard TDT requires that both parents can be genotyped, which is often a serious complications. Sib-based (S-TDT) tests are starting to be developed.
  • See Ewens and Spielman (1997). "Disease associations and the transmission/disequilibrium test (TDT)" . Current Protocols in Human Genetics, Supplement 15, 1.12.1 - 1.12.13

Identifying And Incorporating Genetic Markers And Major Genes In Animal Breeding Programs by Brian Kinghorn and Julius van der Werf (pdf file). Notes from a course given in Belo Horizonte (Brazil) 31 May to 5 June 2000.

Journals

The Journal of Quantitative Trait Loci (JQTL),, an electronic journal sponsored by the Crop Science Society of America

WWW pages of interest

• Brian Yandell's (U Wisconsin) Genetic Linkage Analysis Web page has lots of nice links related to linkage and gene mapping.

• The Rockerfeller University's Resources in Genetic Linkage Analysis is a very detailed list of information for human linkage analysis.

• Report and Recommendations from the NIH meeting on The Genetic Architecture of Complex Traits held at the (US) National Institutes of Health on December 10-11, 1997.

Programs

• QTL cartographer is a suite of programs out of North Carolina State University (by Chris Basten, Bruce Weir, and Shaobang Zeng) designed to map quantitative trait loci (QTLs) onto a genetic linkage map using linear regression and interval or composite interval mapping. It includes programs to simulate or translate data files, do analyses and reformat the analytical results for graphical presentation.
  • .

  • Statistical Analysis for Genetic Epidemiology (S.A.G.E.) is a software package containing more than 20 programs for use in genetic analysis of family and pedigree data. The software is available for several platforms. Here are some of the programs:
    1. AGEON : Estimates the Distribution of Age-of-Onset - in the presence of non-susceptible persons. This information can be used in SIBPAL.
    2. ASSOC: Marker-Trait Association - allows for estimating and testing the association between a quantitative trait and a genetic marker in pedigree data.
    3. BCROSS: Genetic Hypothesis Testing from Data on Inbred Strains, their F1 and Backcross(es) - test one locus, two-locus and polygenic hypotheses for quantitative data.
    4. CLUSTR: Power Transformation to Obtain Normality and Homoscedasticity from Clustered Data - can be used to obtain an appropriate transformation for data that are to undergo analysis with BCROSS.
    5. DESPAIR: Design of linkage studies that are based on affected pairs of relatives - determines the optimal two-stage study design for such studies.
    6. FCOR : Familial Correlations - estimates familial correlations for all types of relatives up to third degree, including cross-correlations for up to five traits.
    7. FSP: Family Structure Program - used to check pedigree data for common structural errors as well as consanguineous matings and loops,
    8. LODLINK: Lod Score Linkage Analysis - which performs two-point linkage analysis between a trait and each of a set of markers.
    9. MAPLOC: Mapping a Disease-Related Trait Relative to a Set of Linked Markers - assumes a fixed map for a set of markers to find the best relative position for a trait locus.
    10. REGC, REGD, REGTL, REGTN: Segregation Analysis Programs - reforms analyses based on regressive models. Information from these programs can be further processed by LODLINK.
    11. RELATE : Relationship to Proband - determines, for single proband pedigrees, the relationship of each individual in the pedigree to the proband.
    12. RELPAL: Relative Pair Linkage Analysis - which screens for genetic linkage of a continuous trait to markers on the basis of relative pair relationships.
    13. SIBPAL : Sib-Pair Linkage Analysis - which screens for genetic linkage on the basis of sib-pair relationships. It can also be used for ordering marker loci.
    14. TDTEX : Exact Test for Transmission Disequilibrium - implements several asymptotic and exact versions of the transmission disequilibrium test (TDT).

  • GREGOR: Software for genetic simulation is a DOS program by Nick Tinker (Department of Plant Science, McGill) which allows students and scientists to explore potential manifestations of genetic models and stochastic processes. It also provides a means to evaluate the effectiveness of statistical procedures such as linkage analysis or QTL detection. GREGOR was developed to fulfil the need for an interactive, user friendly method of performing genetic simulation. It provides procedures for defining genetic models, manipulating genetic populations, and examining simulated data. Models may be designed for simple mendelian traits as well as quantitative traits that are affected by multiple genes and/or environment. Using graphical output, users can observe the segregation of genes in simulated genetic populations.

  • MQTL: Software for simplified composite QTL interval mapping is a DOS/Unix program by Nick Tinker (Department of Plant Science, McGill) for QTL mapping. Two complementary procedures are built into MQTL: The first performs simple interval mapping (SIM) using linear models of the type described by Haley and Knott (1992). This gives results that are very similar to those obtained with the maximum- likelihood methods implemented in Mapmaker/QTL (Lincoln et al., 1992). The second procedure performs a simplified type of composite interval mapping (sCIM), also based on linear models. The principle behind sCIM is to test for the presence of a single QTL at specific locations in a genome while simultaneously accounting for the effects of other QTL. This is done by including partial regression coefficients for a set of "background markers". Both procedures have been extended to provide a test for QTL-by-environment interaction based on the assumption that environments are fixed. More info.

  • MSIM: Software for Automated Simulation of genetic markers and QTL is a DOS/Unix program by Nick Tinker (Department of Plant Science, McGill) that provides an automated method for simulating marker genotypes and quantitative trait phenotypes in populations. The model is specified by parameters given in a small ASCII input file. Output is produced in a format that can be read by the QTL analysis software MQTL.

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  Volume One Chapters --- 1. An Overview of Quantitative Genetics 2. Properties of Distributions 3. Covariance, Regression, and Correlation 4. Properties of Single Loci 5. Components of Genetic Variation 6. Components of Environmental Variation 7. Resemblance Between Relatives 8. Matrix Algebra and Multiple Regression 9. Analysis of Line Crosses 10. Inbreeding and Outbreeding Depression 11. Matters of Scale 12. Polygenes and Polygenic Mutation 13. Detecting Major Genes 14. Principles of Marker-Based Analysis 15. Mapping and Characterizing QTL: Inbred Line Crosses 16. Mapping and Characterizing QTL: Outbred Populations 17. Parent-Offspring Regression 18. Sib Analysis 19. Twins and Clones 20. Cross-classified Designs 21. Correlated Characters 22. Genotype X Environment Interaction 23. Maternal Effects 24. Sex-linked Inheritance and Sexual Dimorphism 25. Threshold Characters 26. Estimation of Breeding Values 27. Variance-Component Estimation in Complex Pedigrees A1. Expectations, Variance, and Covariance of Compound Variables A2. Path Analysis A3. Further Topics in Matrix Algebra A4. Maximum Likelihood Estimation and Likelihood Ratio Tests A5.Computing the Power of Statistical Test

  Home Pages: [ Volume One ] - [ Volume Two ] - [ What's new ] - [ Book]

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  Created 25 February 1995, last updated 11 April 2001

  Bruce Walsh. jbwalsh@u.arizona.edu . Comments welcome.