
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

39149335
10.1101/2024.08.11.607269
preprint
2
Article
Genotyping sequence-resolved copy-number variation using pangenomes reveals paralog-specific global diversity and expression divergence of duplicated genes
Ma Walfred http://orcid.org/0000-0001-8650-5541

Chaisson Mark JP http://orcid.org/0000-0001-5395-1457

29 8 2024
2024.08.11.607269https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.08.11.607269
nihpp-2024.08.11.607269.pdf
Abstract

Human pangenomes contain assemblies of non-reference copy-number variable (CNV) genes. We developed a new method, ctyper, to identify the copy-number of specific alleles of CNV genes cataloged in pangenomes with NGS datasets. Applying ctyper to the 1000-genomes samples revealed population stratification of paralogs and two classes of CNVs: recent CNVs due to ongoing duplications, and polymorphic CNVs from non-reference ancient paralogs. Expression quantitative trait locus analysis determined allele-specific expression within gene families, revealing that 7.94% of paralogs and 3.28% orthologs had significantly divergent expression. Case studies of individual genes include finding lower expression on SMN -1 copies that arose from conversion from SMN- 2, and increased expression on a form of AMY2B that has undergone a translocation. Moreover, 4.7% of paralogs and 1.2% of orthologs had different most-expressed tissues. Furthermore, the genotypes explain more expression variance than known eQTL variants. Overall, ctyper enables biobank-scale genotyping of sequence-resolved CNVs.
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pmc
