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Cited by 75Genomics and Phylogenetic StudiesGenomics and Rare DiseasesGenetic Associations and Epidemiology

Human Genome Sequencing at the Population Scale: A Primer on High-Throughput DNA Sequencing and Analysis

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Goldfeder, Rachel L, Wall, Dennis P, Khoury, Muin J, Ioannidis, John P A, Ashley, Euan A·2017·American Journal of Epidemiology
DOI 10.1093/aje/kww224PMC PMC6250075
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Abstract

Most human diseases have underlying genetic causes. To better understand the impact of genes on disease and its implications for medicine and public health, researchers have pursued methods for determining the sequences of individual genes, then all genes, and now complete human genomes. Massively parallel high-throughput sequencing technology, where DNA is sheared into smaller pieces, sequenced, and then computationally reordered and analyzed, enables fast and affordable sequencing of full human genomes. As the price of sequencing continues to decline, more and more individuals are having their genomes sequenced. This may facilitate better population-level disease subtyping and characterization, as well as individual-level diagnosis and personalized treatment and prevention plans. In this review, we describe several massively parallel high-throughput DNA sequencing technologies and their associated strengths, limitations, and error modes, with a focus on applications in epidemiologic research and precision medicine. We detail the methods used to computationally process and interpret sequence data to inform medical or preventative action.

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  • Whole-genome alignments provide a global perspective on genomic similarity and variation, yielding insights into species' evolution, gene function, and genetic diseases.

    “WGAs provide a global perspective on genomic similarity and variation, yielding insights into species' evolution, gene function, and genetic diseases [2].”

    From Whole-Genome Alignment: Methods, Challenges, and Future Directions (2024) · cites this paper as [2]

    The Methodology and Genotype and variant detection sections describe aligning human sequence reads to a reference genome to identify variation, including variants relevant to disease. They do not describe whole-genome alignments between species or attribute insights into species’ evolution or gene function to those alignments. No page numbers are available in our copy. (LLM, conf=0.84)

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Authors
Goldfeder, R. L., Wall, D. P., Khoury, M. J., Ioannidis, J. P. A., & Ashley, E. A.
Affiliations
Stanford Medicine (US)
Corresponding author
Ashley, Euan A
ORCID
Venue
American Journal of Epidemiology
Publisher
Oxford University Press (OUP)
Published
2017-05-10
Volume
186
Issue
8
Pages
1000-1009
ISSN
  • 0002-9262 (ISSN-L)
  • 1476-6256
DOI
10.1093/aje/kww224
PMC
PMC6250075
OpenAlex
W2612293414
Cited by
75
References
4
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 20 · 2019: 12 · 2018: 6 · 2017: 1
FWCI
0.57
Type
journal article
Language
en
Open access
Locations
  • American Journal of Epidemiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Library of Medicine (T15 LM7033, U01FD004979)
  • Food and Drug Administration
  • National Science Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
human genome sequencing, next-generation sequencing, population-scale genomics, sequence data analysis, precision medicine, disease subtyping, personalized medicine
MeSH terms
Humans, Genome, Human, Sequence Analysis, DNA, Genetic Predisposition to Disease, Genomics, High-Throughput Nucleotide Sequencing

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