Article Abstract:
A method has been developed to overcome a problem that comes up in some methods of studying genetic aspects of complex diseases. It makes possible application of the transmission/disequilibrium test (TDT) using marker data from unaffected siblings instead of from parents and is called the 'sib TDR' or 'S-TDR' method. All data may be used together in an overall TDT type of procedure to test for linkage in the presence of association. Linkage analysis with genetic markers has been useful in the localizing genes for many monogenic human diseases. In studies of complex diseases, however, tests that depend on linkage disequilibrium, the presence of association and linkage at the same time, are often more useful than those that rely on linkage only. The advantage can be seen by TDT, which requires data, that is, marker genotypes, for affected individuals and their parents. For some diseases parent data may not be available. Study of diseases of late onset and of those associated with aging may be advanced using extension of the TDT.
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Article Abstract:
Low-density lipoprotein (LDL) size has been linked to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency. The genetic linkage of LDL particle size to the lipoprotein lipase (LpL) gene was studied in five families with structural mutations in the LpL gene. LDL particle size was smaller in heterozygous subjects vs controls. Using the quantitative trait adjusted for variance within the genotype and coming from physiologic covariates was essential for detection of significant evidence of linkage. LpL is a rate-limiting enzyme in formation of LDL particles.
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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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