The impact of transmission-ratio distortion on allele sharing in affected sibling pairs.
There have been recent reports of transmission-ratio distortion (TRD) or segregation distortion in families not selected for genetic disease. If TRD exists but is ignored, linkage studies searching for disease genes in affected relatives may be misinterpreted. We show that the identical-by-descent sharing patterns for affected sib pairs are strongly affected by TRD and, further, that the estimated statistical significance of a sib-pair linkage study may be extremely biased. However, we also show that, if TRD is suspected during the planning stage of a study, the planned sample size of the study needs to be increased by only a small amount to maintain the desired power.
Greenwood
C M
CM
Division of Medical Genetics, Montreal General Hospital, Montreal QC H3G 1A4, Canada. celia@bagel.epi.mcgill.ca
Morgan
K
K
D000483:Alleles; D015982:Bias; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D009679:Nuclear Family; D018401:Sample Size; D012727:Sex Characteristics