The conservation of human functional variants and their effects across livestock species View Full Text


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Article Info

DATE

2022-09-21

AUTHORS

Rongrong Zhao, Andrea Talenti, Lingzhao Fang, Shuli Liu, George Liu, Neil P. Chue Hong, Albert Tenesa, Musa Hassan, James G. D. Prendergast

ABSTRACT

Despite the clear potential of livestock models of human functional variants to provide important insights into the biological mechanisms driving human diseases and traits, their use to date has been limited. Generating such models via genome editing is costly and time consuming, and it is unclear which variants will have conserved effects across species. In this study we address these issues by studying naturally occurring livestock models of human functional variants. We show that orthologues of over 1.6 million human variants are already segregating in domesticated mammalian species, including several hundred previously directly linked to human traits and diseases. Models of variants linked to particular phenotypes, including metabolomic disorders and height, are preferentially shared across species, meaning studying the genetic basis of these phenotypes is particularly tractable in livestock. Using machine learning we demonstrate it is possible to identify human variants that are more likely to have an existing livestock orthologue, and, importantly, we show that the effects of functional variants are often conserved in livestock, acting on orthologous genes with the same direction of effect. Consequently, this work demonstrates the substantial potential of naturally occurring livestock carriers of orthologues of human functional variants to disentangle their functional impacts. More... »

PAGES

1003

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s42003-022-03961-1

    DOI

    http://dx.doi.org/10.1038/s42003-022-03961-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1151187782

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/36131008


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