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Comprehensive variant discovery in the era of complete human reference genomes

Nature Methods volume 20, pages 17–19 (2023)Cite this article

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Advances in long-read sequencing technologies have broadened our understanding of genetic variation in the human population, uncovered new complex structural variants and offered an opportunity to elucidate new variant associations with disease.

Recent sequencing innovations in both read length and accuracy have led to the emergence of complete, telomere-to-telomere chromosome assemblies1, and uncovered new complex structural variants2. Additionally, as long-read sequencing becomes more economical and available for large-scale production, our understanding of rare and common variants across diverse human haplotypes will become more comprehensive. A complete assessment of variation, small and large, offers an opportunity to explore sources of hidden heritability. Here we explore the promise that long-read sequencing holds for uncovering complex variants through access to more-complete human reference genomes, and how such resources can support large-scale disease-association studies in the future.

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Fig. 1: Genomic variants and schematics of their location on the chromosome.

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Acknowledgements

K.H.M. and M.C. are supported by NIH/NHGRI U01HG010971.

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Authors and Affiliations

  1. Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA

    Monika Cechova & Karen H. Miga

  2. UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA

    Monika Cechova & Karen H. Miga

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  1. Monika Cechova
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  2. Karen H. Miga
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Correspondence to Karen H. Miga.

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Competing interests

K.H.M. is a science advisory board member of Centaura, Inc. and has received travel funds to speak at events hosted by Oxford Nanopore Technologies.

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Cechova, M., Miga, K.H. Comprehensive variant discovery in the era of complete human reference genomes. Nat Methods 20, 17–19 (2023). https://doi.org/10.1038/s41592-022-01740-8

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