RESUMO
Osteoporosis attacks 10% of the population worldwide. Humans or even the model animals of the disease cannot recover from porous bone. Regeneration in skeletal elements is the unique feature of our newly investigated osteoporosis model, the red deer (Cervus elaphus) stag. Cyclic physiological osteoporosis is a consequence of the annual antler cycle. This phenomenon raises the possibility to identify genes involved in the regulation of bone mineral density on the basis of comparative genomics between deer and human. We compare gene expression activity of osteoporotic and regenerating rib bone samples versus autumn dwell control in red deer by microarray hybridization. Identified genes were tested on human femoral bone tissue from non-osteoporotic controls and patients affected with age-related osteoporosis. Expression data were evaluated by Principal Components Analysis and Canonical Variates Analysis. Separation of patients into a normal and an affected group based on ten formerly known osteoporosis reference genes was significantly improved by expanding the data with newly identified genes. These genes include IGSF4, FABP3, FABP4, FKBP2, TIMP2, TMSB4X, TRIB, and members of the Wnt signaling. This study supports that extensive comparative genomic analyses, here deer and human, provide a novel approach to identify new targets for human diagnostics and therapy.
Assuntos
Densidade Óssea/genética , Regeneração Óssea/genética , Cervos/genética , Cervos/fisiologia , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/fisiopatologia , Idoso , Animais , Estudos de Casos e Controles , DNA/genética , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Componente Principal , Especificidade da Espécie , Proteínas Wnt/genéticaRESUMO
A novel discrete mathematical approach is proposed as an additional tool for molecular systematics which does not require prior statistical assumptions concerning the evolutionary process. The method is based on algorithms generating mathematical representations directly from DNA/RNA or protein sequences, followed by the output of numerical (scalar or vector) and visual characteristics (graphs). The binary encoded sequence information is transformed into a compact analytical form, called the Iterative Canonical Form (or ICF) of Boolean functions, which can then be used as a generalized molecular descriptor. The method provides raw vector data for calculating different distance matrices, which in turn can be analyzed by neighbor-joining or UPGMA to derive a tree, or by principal coordinates analysis to get an ordination scattergram. The new method and the associated software for inferring phylogenetic trees are called the Boolean analysis or BOOL-AN.