Publication Date
8-1-2023
Journal
Nature Methods
DOI
10.1038/s41592-023-01914-y
PMID
37365340
PMCID
PMC10406601
PubMedCentral® Posted Date
6-26-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Male, Humans, Genomics, Genome, Human, Major Histocompatibility Complex, Software, Genome assembly algorithms, Structural variation, Genome assembly algorithms
Abstract
Advancements in sequencing technologies and assembly methods enable the regular production of high-quality genome assemblies characterizing complex regions. However, challenges remain in efficiently interpreting variation at various scales, from smaller tandem repeats to megabase rearrangements, across many human genomes. We present a PanGenome Research Tool Kit (PGR-TK) enabling analyses of complex pangenome structural and haplotype variation at multiple scales. We apply the graph decomposition methods in PGR-TK to the class II major histocompatibility complex demonstrating the importance of the human pangenome for analyzing complicated regions. Moreover, we investigate the Y-chromosome genes, DAZ1/DAZ2/DAZ3/DAZ4, of which structural variants have been linked to male infertility, and X-chromosome genes OPN1LW and OPN1MW linked to eye disorders. We further showcase PGR-TK across 395 complex repetitive medically important genes. This highlights the power of PGR-TK to resolve complex variation in regions of the genome that were previously too complex to analyze.
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons
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