Role of duplicate genes in determining the tissue-selectivity of hereditary diseases.
作者： Ruth Barshir , Idan Hekselman , Netta Shemesh , Moran Sharon , Lena Novack
DOI: 10.1371/JOURNAL.PGEN.1007327
关键词:
摘要: A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds hereditary diseases to certain tissues, while their causal genes are expressed throughout body. general conception that tissue-selective disease phenotypes emerge when masking factors operate unaffected but specifically absent or insufficient disease-manifesting tissues. Although this has critical impact on understanding manifestation, it was never challenged a systematic manner across variety and affected Here, we address gap our via rigorous analysis susceptibility over 30 tissues 112 diseases. We focused roles paralogs genes, which presumably capable compensating for aberration. show first time at large-scale quantitative omics datasets that, preferentially under-expressed relative more than half This observed several susceptible with varying number paralogs, suggesting imbalanced expression increases tissue susceptibility. While many imbalance stemmed from up-regulation gene other often combined down-regulation its paralog. Notably roughly 20% cases, only significant Thus, dosage relationships between appear as important, yet currently under-appreciated, modifiers manifestation.
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