Possible linkage of a breast cancer‐susceptibility locus to theABOlocus: Sensitivity of LOD scores to a single new recombinant observation

摘要

AbstractWe present evidence of a pedigree in which a major gene for breast cancer‐susceptibility appears to segregate in a dominant fashion. Linkage analysis suggests that the breast cancer‐susceptibility locus in this family may be linked to theABOlocus, which is located on band q34 of chromosome 9. At an early stage in the analysis, a LOD score of 3.0 for zero recombination was obtained for linkage betweenABOand the susceptibility locus, but a single recombinant reduced the LOD score to 1.72 at a recombination fraction of 0.06. A final observation of a nonrecombinant brings the LOD score for this pedigree to 1.99 atdocumentclass{article}pagestyle{empty}begin{document}$documentclass{article}pagestyle{empty}begin{document}$ widehat{rm{theta }} $end{document}$end{document}= 0.05. We attempt to put these results in perspective by discussing the sensitivity of the LOD score to the next observation. Examples of the volatility of LOD scores are given. These simple calculations show that tight linkage represents the worst case for the interpretation of a LOD score of 3.0. Finally, we discuss the linkage between the breast cancer‐susceptibility locus and theABOblood group and approaches to confirming or denying this r