Biomedical Engineering Reference
In-Depth Information
Figure 14
. The top diagram emphasizes the tripartite division of influences that shape an organ-
ism, namely the genome, epigenome, and environment. The set of all possible behaviors for an
organism (i.e., communication) is determined by these three influences, although the specific
sequence of output is not. The internal environment produced by the genome/epigenome (bottom)
produces the putative spatiotemporal scales of brain function. In this case, activity at the level of
distributed groups of cells, local networks or groups of cells, and individual neurons modulate the
function of the genome/epigenome, and activity at the level of the genome/epigenome signifi-
cantly modulates the function of each of the spatiotemporal scales of function that embed it. The
linked spatiotemporal scales of brain function are again distinct from observed behavior in the
outside world (i.e., exophenotype) and will have a stronger connection, as endophenotypes ob-
servable with neuroimaging and other measurement systems of brain function, with the ge-
nome/epigenome. The scale of distributed groups of cells produces behavior, and accordingly
serves as an interface between the environment and genome/epigenome.
neurodevelopmental etiologies (34,150,245). For instance, prion diseases and
many of the neurodegenerative diseases with patterns of mixed Mendelian
and/or non-Mendelian inheritance (i.e., Alzheimer's disease, Parkinson's disease,
frontotemporal dementias, Huntington's disease) have a strong component of
their etiology from two processes. One process involves the dysfunction and/or
cell death of a subset of brain neurons/glia that express an aberrant gene product,
whereas a second process involves the non cell-autonomous consequences (e.g.,
altered homeostasis) of this cellular vulnerability. These diseases result from an
inability to maintain mutant proteins: (a) in a properly folded and/or functional
state, (b) in their proper subcellular organelles, or (c) at appropriate steady-state
levels to prevent their gain-of-function role (59,64,85,111,118,124,183,191,