LINKAGE ANALYSIS OF A COMMON OLIGOGENIC DISEASE USING SELECTED SIB PAIRS

Sib pairs drawn from the simulated common oligogenic disease families were selected for extreme quantitative trait scores and analyzed using interval mapping and multipoint methods. Linkage analyses of 112 sele cted sib pairs, in which one or more members had trait values exceedin g the disease threshold, were compared with analyses of the total unse lected sib-pair sample (771 pairs). Selected sample regression models yielded comparable significance levels to those obtained from the unse lected sample at most loci on the six simulated chromosomes, demonstra ting the efficiency of selected sib-pair analysis for quantitative cha racters. Two of the three disease QTLs were detected in both selected and unselected samples. Interval mapping and multipoint analyses yield ed location estimates close to the simulated positions of the QTLs. Th e combined strategy of using interval mapping and multipoint methods w ith selected sib pairs appears to provide improved accuracy and sensit ivity over more traditional sib-pair methods for detecting quantitativ e trait loci. (C) 1995 Wiley-Liss, Inc.