QTLMap

Authors

  • P. Le Roy, INRA
  • JM. Elsen, INRA
  • H. Gilbert, INRA
  • C. Moreno, INRA
  • A. Legarra, INRA
  • O. Filangi(contact), INRA

Website

http://www.inra.fr/qtlmap

Background

QTLmap is a linkage analysis software dedicated to the analysis of outbred population in an experimental design. This software is developed at INRA (french National Institute for Agronomical Research) to map following linkage analyses approaches in various experimental populations. Specific models were implemented to take maximum advantage of large data sets now available for QTL detection and get fine locus descriptions (indications of pleiotropy, of linked loci…)to facilitate further explorations. In QTLMAP, the basis of the QTL detection technique is an interval mapping applied to half-sib families or a mixture of full- and half-sib families where the exact computation of phase probability is undertaken from a 2 or 3 generation pedigree. The test statistics are computed either using exact calculation of likelihood ratios or using partial linear approximations of the likelihood or complete regression on marker genotypes.

Various genetic models will be proposed depending on 1) the QTL allele segregation (biallelic in crosses between monomorphic breeds, biallelic without hypothesis on the origin, multiallelic, haplotype identity), 2) the number of QTL segregating (one, two linked, several unlinked), 3) the number of traits under the QTL influence. The trait determinism is envisaged depending on 1) the trait distribution (gaussian trait, survival trait or threshold distribution), 2) the interactions between the QTL and fixed effects or other loci, 3) the residual variance structure (homo- or heteroskedasticity for half-sib families). Due to differences with the asymptotical conditions from the chi2 theory, the test statistic significance are evaluated either through numerical approximations, or through empirical calculations obtained from permutations or simulations under the null hypothesis.

Finally, the software will be released in coordination with procedures for data verification to facilitate genotyping validations and trait evaluations of data sets.

Available Functionnalities

Up to now, the following functionnalities have been implemented :
  • QTL detection in half-sib families or mixture of full- and half-sib families
  • One or two linked QTL segregating in the population
  • Single trait or multiple trait analyses
  • Nuisance parameters (e.g. sex, batch, weight...) and their interactions with QTL can be included in the analysis
  • Gaussian, discrete or survival (Cox model) data
  • Familial heterogeneity of variances (heteroscedasticity)
  • Can handle eQTL analyses
  • Computation of transmission and phase probabilities adapted to high throughput genotyping (SNP)
  • Empirical thresholds are estimated using simulations under the null hypothesis or permutations of trait values
  • Computation of power and accuracy of your design or any simulated design

References

  • Knott SA, Elsen JM, Haley CS, 1996. Methods for multiple marker mapping of quantitative trait loci in half-sib populations. Theor. Appl. Genet. : 93 : 71-80.
  • Elsen JM, Mangin B, Goffinet B, Boichard D, Le Roy P, 1999. Alternative models for QTL detection in livestock. I. General introduction. Genet. Sel. Evol., 31, 213-224
  • Mangin B, Goffinet B, Le Roy P, Boichard D, Elsen JM, 1999. Alternative models for QTL detection in livestock. II. Likelihood approximations and sire marker genotype estimations. Genet. Sel. Evol., 31, 225-237.
  • Goffinet B, Le Roy P, Boichard D, Elsen JM, Mangin B, 1999. Alternative models for QTL detection in livestock. III. Heteroskedastic model and models corresponding to several distributions of the QTL effect.. Genet. Sel. Evol., 31, 341-350.
  • Moreno C.R., Elsen J.M., Le Roy P., Ducrocq V., 2005. Interval mapping methods for detecting QTL affecting survival and time–to–event phenotypes. Genet. Res. Camb., 85 : 139-149.
  • Gilbert H, Le Roy P., 2007. Methods for the detection of multiple linked QTL applied to a mixture of full and half sib families. Genet Sel Evol., 39(2):139-58.
  • Gilbert H., Le Roy P., Moreno C., Robelin D., Elsen J. M., 2008. QTLMAP, a software for QTL detection in outbred population. Annals of Human Genetics, 72(5): 694.
  • Filangi.O , Moreno C. , Gilbert H. , Legarra A. , Le Roy P. , Elsen JM. QTLMap, a software for QTL detection in outbred populations. 9th World Congress on Genetics Applied to Livestock Production, Leipzig. 2010.