Document Type

Article

Publication Date

2-1-2025

Publication Title

Nature genetics

Keywords

JGM, Humans, Segmental Duplications, Genomic, Genome, Human, DNA Copy Number Variations, Polymorphism, Genetic, Genetics, Population, Black People

JAX Source

Nat Genet. 2025;57(2):390-401.

Volume

57

Issue

2

First Page

390

Last Page

401

ISSN

1546-1718

PMID

39779957

DOI

https://doi.org/10.1038/s41588-024-02051-8

Abstract

Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.2 Mb of duplicated sequence (47.4 Mb not present in the telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. We find that intrachromosomal SDs are among the most variable, with rare events mapping near their progenitor sequences. African genomes harbor significantly more intrachromosomal SDs and are more likely to have recently duplicated gene families with higher copy numbers than non-African samples. Comparison to a resource of 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding to these copy number polymorphic SDs.

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