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Should ambiguous trios for the TDT be discarded?
Author(s) -
SHAM P. C.,
ZHAO J. H.,
WALDMAN I.,
CURTIS D.
Publication year - 2000
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1469-1809.2000.6460575.x
Subject(s) - allele , genotype , genetics , statistic , biology , offspring , statistics , mathematics , gene , pregnancy
It is well known that the TDT proposed by Spielman et al . (1993) is potentially anti‐conservative if families with one missing parental genotype are included (Curtis & Sham, 1995). We now bring attention to another situation that could give rise to an inflated rate of false positive results. This occurs when families in which the affected offspring and both parents have the same heterozygous genotype are excluded. If the heterozygous genotype is denoted as AB, then it is clear that one parent must have transmitted allele A and the other allele B. The standard TDT procedure is to increment the counts for transmissions of both A and B by one. It may seem reasonable to disregard such trios because it is ambiguous which parent has transmitted which allele. Although the resulting test statistic would retain all the information concerning preferential transmission of alleles, it can be shown that referring it to a χ 2 distribution would lead to an increased type I error rate (see Appendix A).