Daniel Gudbjartsson

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deCODE Genetics, Iceland


Multipoint Linkage Analysis based on Allele Sharing Models

Several improvements to computational algorithms for multipoint linkage analysis are developed. The new algorithms achieve considerable speed-up over previous ones and allow larger families to be analyzed. The algorithms have been implemented into a computer program, Allegro. Allegro directly incorporates the statistical methods based on allele sharing models of Kong and Cox (1997) and also performs most of the standard calculations associated with linkage analysis like haplotyping and estimation of recombination fractions. The methods based on allele sharing models are also extended to quantitative trait locus (QTL) linkage analysis. The most popular methods to detect linkage to a QTL have been the Haseman-Elston tests and methods referred to as variance components methods. The accuracy of type I error rates for allele sharing models is demonstrated, even in the presence of selection where the variance components methods fail. The relationship of the allele sharing models to the Haseman-Elston tests is discussed, and it is shown that the power of allele sharing models based on the Haseman-Elston tests is greater than that of the original test. The QTL linkage analysis based on allele sharing models may easily be extended to general families, contrary to the Haseman-Elston tests, which are difficult to extend beyond sib-ships.