A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. McParland, D Phillips, C M Brennan, L Roche, H M Gormley, I C PMID:27996060Ĭlustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data. These findings have challenging implications for efforts to identify human disease correlates. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Mohun, Timothy Weninger, Wolfgang J.īackground: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Reissig, Lukas Rose, Julia Szumska, Dorota Hardman, Emily Prin, Fabrice McGuire, Christina Ramirez-Solis, Ramiro White, Jacqui Galli, Antonella Tudor, Catherine Tuck, Elizabeth Mazzeo, Cecilia Icoresi Smith, James C. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice
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