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Review
. 2020 Mar;21(3):137-150.
doi: 10.1038/s41576-019-0200-9. Epub 2020 Jan 8.

Mechanisms of tissue and cell-type specificity in heritable traits and diseases

Idan Hekselman  1 , Esti Yeger-Lotem  2   3
Affiliations
Review

Mechanisms of tissue and cell-type specificity in heritable traits and diseases

Idan Hekselman et al. Nat Rev Genet. 2020 Mar.

Abstract

Hundreds of heritable traits and diseases that are caused by germline aberrations in ubiquitously expressed genes manifest in a remarkably limited number of cell types and tissues across the body. Unravelling mechanisms that govern their tissue-specific manifestations is critical for our understanding of disease aetiologies and may direct efforts to develop treatments. Owing to recent advances in high-throughput technologies and open resources, data and tools are now available to approach this enigmatic phenomenon at large scales, both computationally and experimentally. Here, we discuss the large prevalence of tissue-selective traits and diseases, describe common molecular mechanisms underlying their tissue-selective manifestation and present computational strategies and publicly available resources for elucidating the molecular basis of their genotype-phenotype relationships.

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References

    1. Lage, K. et al. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. Proc. Natl Acad. Sci. USA 105, 20870–20875 (2008). A pioneering large-scale analysis of expression mechanisms in the context of tissue-selective hereditary diseases. - PubMed - PMC - DOI
    1. Barshir, R. et al. Role of duplicate genes in determining the tissue-selectivity of hereditary diseases. PLOS Genet. 14, e1007327 (2018). - PubMed - PMC - DOI
    1. Barshir, R., Shwartz, O., Smoly, I. Y. & Yeger-Lotem, E. Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases. PLOS Comput. Biol. 10, e1003632 (2014). Tissue-specific protein interaction maps and their relationship to the tissue selectivity of hereditary diseases. - PubMed - PMC - DOI
    1. Bamshad, M. J. et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat. Rev. Genet. 12, 745–755 (2011). - PubMed - DOI
    1. Moaven, N., Tayebi, N., Goldin, E. & Sidransky, E. Rare Diseases Advances in Predictive, Preventive and Personalised Medicine 69-90 (Springer Netherlands, 2015).

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