Simultaneous fine mapping of closely linked epistatic quantitative trait loci using combined linkage disequilibrium and linkage with a general pedigree

Causal mutations and their intra- and inter-locus interactions play a critical role in complex trait variation. It is often not easy to detect epistatic quantitative trait loci (QTL) due to complicated population structure requirements for detecting epistatic effects in linkage analysis studies and due to main effects often being hidden by interaction effects. Mapping their positions is even harder when they are closely linked. The data structure requirement may be overcome when information on linkage disequilibrium is used. We present an approach using a mixed linear model nested in an empirical Bayesian approach, which simultaneously takes into account additive, dominance and epistatic effects due to multiple QTL. The covariance structure used in the mixed linear model is based on combined linkage disequilibrium and linkage information. In a simulation study where there are complex epistatic interactions between QTL, it is possible to simultaneously map interacting QTL into a small region using the proposed approach. The estimated variance components are accurate and less biased with the proposed approach compared with traditional models.     

Comparative usefulness of cytology and peroxidase activity in conjunction with carcinoembryonic antigen levels for the diagnosis of mammary cancer

Diagnosis of cancer via measurement of carcinoembryonic antigen (CEA) levels has been unreliable in early neoplastic stages. In order to improve diagnostic reliability, other cytological parameters were examined with CEA. Fifty specimens of effusion fluid were obtained from 40 hospitalized patients and the levels of CEA determined by radioimmunoassay in conjunction with application of an immunoperoxidase procedure. Simultaneous morphologic assessment was performed without knowledge of the immunoassay findings. In 8 documented cases of mammary cancer, all effusion fluid specimens had CEA levels of 16-1074 ng/ml, 7 cases had morphologically positive cells, but only 3 had a peroxidase positive reaction. Except for one case of ovarian papillary adenocarcinoma, the remaining patients were cancer free, had CEA levels of less than 15 ng/ml and only 2 cases (including the ovarian tumor patient) gave positive peroxidase responses. The presence of mammary metastatic duct carcinoma correlated 88% with CEA measurements but peroxidase response was not diagnostically helpful.