Language
English
Publication Date
3-1-2025
Journal
Nature Biotechnology
DOI
10.1038/s41587-024-02225-z
PMID
38671154
PMCID
PMC11952744
PubMedCentral® Posted Date
3-28-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits and are linked to over 60 disease phenotypes. However, they are often excluded from at-scale studies because of challenges with variant calling and representation, as well as a lack of a genome-wide standard. Here, to promote the development of TR methods, we created a catalog of TR regions and explored TR properties across 86 haplotype-resolved long-read human assemblies. We curated variants from the Genome in a Bottle (GIAB) HG002 individual to create a TR dataset to benchmark existing and future TR analysis methods. We also present an improved variant comparison method that handles variants greater than 4 bp in length and varying allelic representation. The 8.1% of the genome covered by the TR catalog holds ~24.9% of variants per individual, including 124,728 small and 17,988 large variants for the GIAB HG002 'truth-set' TR benchmark. We demonstrate the utility of this pipeline across short-read and long-read technologies.
Keywords
Humans, Genome, Human, Benchmarking, Genetic Variation, Tandem Repeat Sequences, Haplotypes, Genomics
Published Open-Access
yes
Recommended Citation
English, Adam C; Dolzhenko, Egor; Ziaei Jam, Helyaneh; et al., "Analysis and Benchmarking of Small and Large Genomic Variants Across Tandem Repeats" (2025). Faculty and Staff Publications. 5120.
https://digitalcommons.library.tmc.edu/baylor_docs/5120
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons