Vanderbilt University

About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.

Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development

Abstract: Bone Morphogenetic Proteins (BMPs) play crucial roles in a variety of developmental processes, but their functions during early vertebrate brain development are largely unknown. To investigate this problem, we have compared by in situ hybridization the expression of five Bmp genes belonging to the Drosophila Decapentaplegic (Bmp2 and Bmp4) and 60A subgroups (Bmp5, Bmp6 and Bmp7). Striking co-expression of these Bmps is observed within the dorsomedial telencephalon, coincident with a future site of choroid plexus development. Bmp co-expression overlaps that of Msx1 and Hfh4, and is complementary to that of Bf1. The domain of Bmp co-expression is also associated with limited growth of the neuroectoderm, as revealed by morphological observation, reduced cell proliferation, and increased local programmed cell death. In vitro experiments using explants from the embryonic lateral telencephalic neuroectoderm reveal that exogenous BMP proteins (BMP4 and BMP2) induce expression of Msx1 and inhibit Bf1 expression, a finding consistent with their specific expression patterns in vivo. Moreover, BMP proteins locally inhibit cell proliferation and increase apoptosis in the explants. These results provide evidence that BMPs function during regional morphogenesis of the dorsal telencephalon by regulating specific gene expression, cell proliferation and local cell death.

The Ubiquitous Nature of Epistasis in Determining Susceptibility to Common Human Diseases

Abstract: There is increasing awareness that epistasis or gene-gene interaction plays a role in susceptibility to common human diseases In this paper, we formulate a working hypothesis that epistasis is a ubiquitous component of the genetic architecture of common human diseases and that complex interactions are more important than the independent main effects of any one susceptibility gene This working hypothesis is based on several bodies of evidence First, the idea that epistasis is important is not new In fact, the recognition that deviations from Mendelian ratios are due to interactions between genes has been around for nearly 100 years Second, the ubiquity of biomolecular interactions in gene regulation and biochemical and metabolic systems suggest that relationship between DNA sequence variations and clinical endpoints is likely to involve gene-gene interactions Third, positive results from studies of single polymorphisms typically do not replicate across independent samples This is true for both linkage and association studies Fourth, gene-gene interactions are commonly found when properly investigated We review each of these points and then review an analytical strategy called multifactor dimensionality reduction for detecting epistasis We end with ideas of how hypotheses about biological epistasis can be generated from statistical evidence using biochemical systems models If this working hypothesis is true, it suggests that we need a research strategy for identifying common disease susceptibility genes that embraces, rather than ignores, the complexity of the genotype to phenotype relationship