research papers on genetic mutation

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• Review Article
• Published: 28 March 2024

Genetic variation across and within individuals

• Zhi Yu   ORCID: orcid.org/0000-0003-4810-3474 1 , 2   na1 ,
• Tim H. H. Coorens   ORCID: orcid.org/0000-0002-5826-3554 1   na1 ,
• Md Mesbah Uddin   ORCID: orcid.org/0000-0003-1846-0411 1 , 2 ,
• Kristin G. Ardlie 1 ,
• Niall Lennon 1 &
• Pradeep Natarajan   ORCID: orcid.org/0000-0001-8402-7435 1 , 2 , 3  

Nature Reviews Genetics volume  25 ,  pages 548–562 ( 2024 ) Cite this article

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• DNA sequencing
• Genetic variation

Germline variation and somatic mutation are intricately connected and together shape human traits and disease risks. Germline variants are present from conception, but they vary between individuals and accumulate over generations. By contrast, somatic mutations accumulate throughout life in a mosaic manner within an individual due to intrinsic and extrinsic sources of mutations and selection pressures acting on cells. Recent advancements, such as improved detection methods and increased resources for association studies, have drastically expanded our ability to investigate germline and somatic genetic variation and compare underlying mutational processes. A better understanding of the similarities and differences in the types, rates and patterns of germline and somatic variants, as well as their interplay, will help elucidate the mechanisms underlying their distinct yet interlinked roles in human health and biology.

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These authors contributed equally: Zhi Yu, Tim H. H. Coorens.

Authors and Affiliations

Broad Institute of MIT and Harvard, Cambridge, MA, USA

Zhi Yu, Tim H. H. Coorens, Md Mesbah Uddin, Kristin G. Ardlie, Niall Lennon & Pradeep Natarajan

Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

Zhi Yu, Md Mesbah Uddin & Pradeep Natarajan

Department of Medicine, Harvard Medical School, Boston, MA, USA

Pradeep Natarajan

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Contributions

T.H.H.C. and Y.Z. researched the literature. T.H.H.C., P.N. and Y.Z. contributed substantially to discussion of the content. T.H.H.C., M.M.U. and Y.Z. wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Pradeep Natarajan .

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Competing interests.

P.N. reports investigator-initiated grants from Amgen, Apple, Boston Scientific, Novartis and AstraZeneca; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech and Novartis; scientific board membership for Esperion Therapeutics, geneXwell and TenSixteen Bio; and spousal employment at Vertex, all unrelated to the present work. P.N. is a scientific co-founder of TenSixteen Bio, which is a company focused on clonal haematopoiesis but had no role in the present work. The other authors declare no competing interests.

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Yu, Z., Coorens, T.H.H., Uddin, M.M. et al. Genetic variation across and within individuals. Nat Rev Genet 25 , 548–562 (2024). https://doi.org/10.1038/s41576-024-00709-x

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Accepted : 09 February 2024

Published : 28 March 2024

Issue Date : August 2024

DOI : https://doi.org/10.1038/s41576-024-00709-x

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