Incapacitating the evolutionary capacitor: Hsp90 modulation of disease Patricia L Yeyati and Veronica van Heyningen

Western General Hospital, Edinburgh, Scotland, United Kingdom
Human Molecular Genetics (Impact Factor: 6.39). 11/2004; 13 Spec No 2(suppl 2):R225-33. DOI: 10.1093/hmg/ddh254
Source: PubMed


Single gene disorders with Mendelian inheritance patterns have contributed greatly to the identification of genes and pathways implicated in genetic disease. In these cases, molecular analysis predicts disease status relatively directly. However, there are many abnormalities which show familial recurrence and have a clear genetic component, but do not show regular Mendelian segregation patterns. Defining the causative gene for non-Mendelian diseases is more difficult, and even when the underlying gene is known, there is uncertainty for prenatal prediction. However, detailed examination of the different mechanisms that underlie non-Mendelian segregation provides insight into the types of interaction that regulate more complex disease genetics.

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    • "It is plausible that the effect of a risk factor on disease development is influenced by the presence or absence of additional agents. There is strong evidence for such mechanisms in classical monogenic conditions where the effect of mutations can be modified by epistatic interactions with other genetic variants and environmental factors [17], [18]. For example, the effect of phenylalanine hydroxylase mutations on the phenotype of phenylketonuria depends on dietary phenylalanine consumption [19]. "
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    PLoS ONE 05/2014; 9(5):e96578. DOI:10.1371/journal.pone.0096578 · 3.23 Impact Factor
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    • "Network formation and analyses are important tools for systems biology, providing a powerful abstraction of intracellular complex relationships. Most common diseases such as diabetes, schizophrenia, hypertension and cancer, are also believed to be caused by multiple genes (multi-genic) [14]. Recently, genes that have the potential to be involved with several diseases are uncovered through the integration of functional information of proteins and the protein interaction network [15–17]. "
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    PLoS ONE 11/2013; 8(11):e81035. DOI:10.1371/journal.pone.0081035 · 3.23 Impact Factor
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    PLoS ONE 11/2010; 5(11):e13827. DOI:10.1371/journal.pone.0013827 · 3.23 Impact Factor
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