Article Abstract:
Several family-based tests of association have been developed using discordant sib pairs (DSPs), those in which one sib is affected with a disease and the other is not. The tests are based on statistics that compare counts of alleles or genotypes or that test for symmetry in tables of genotypes or alleles. A permutation framework was used to assess the significance of the statistics obtained. For late-onset diseases methods that require genotypes on affected persons and their parents may not be suitable. The properties of the DSP-based tests have been compared by computer simulations. An application to Alzheimer's disease and the apolipoprotein E (apoE) polymorphism is illustrative. The discordant-alleles test seems to be the most powerful among those considered.
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Article Abstract:
Interval and point estimates of marker location are discussed as they relate to radiation hybrid (RH) mapping, a powerful method for ordering loci on chromosomes and estimating distances between them used to set up framework and comprehensive maps. A statistical method for estimating marker position, an alternative to binning, is proposed, a method combining a measure of uncertainly in location for every marker and information from all plausible marker orders.
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Article Abstract:
An extension of one of three recently developed family-based tests of association and linkage using unaffected siblings as surrogates for untyped parents is proposed. The four tests are then compared using as an example the application to a complex disease for both biallelic and multiallelic markers and for sibships of varying sizes, then looking at availability of some parental data.
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