Multidimensional telomere diversity and inheritance at individual and population scales
Variation in telomere length, sequence composition and epigenetic state influences genome stability, aging and disease, yet its high-resolution characterization across species remains challenging. Here we present TeloXplorer, a computational framework for long-read data that jointly profiles telomere length, telomere variant repeats (TVRs) and DNA methylation at chromosome-end and haplotype…
Telomere diversity and inheritance exhibit multidimensional characteristics at both individual and population scales, posing challenges for comprehensive characterization. Researchers have now unveiled TeloXplorer, a computational framework designed to analyze long-read data and jointly profile telomere length, telomere variant repeats (TVRs), and DNA methylation at chromosome-ends and haplotype resolution.
Extensive testing of TeloXplorer across simulated and empirical datasets from humans, Arabidopsis, and yeast demonstrated its ability to accurately resolve chromosome-end-specific telomere features. The tool also identified the critical role of sample-matched, haplotype-resolved assemblies in obtaining accurate results.
Applying TeloXplorer to two human trios revealed a strong correlation between relative telomere-length profiles and the transmission of TVR haplotypes in a Mendelian fashion. Furthermore, methylation patterns within families remained conserved, underscoring the hereditary nature of these telomere-associated traits.
In a broader perspective, TeloXplorer was applied to the genomes of 232 individuals from the Human Pangenome Reference Consortium, representing five continental and 28 population groups. The analysis confirmed that chromosome-end telomere-length rankings remained remarkably consistent across these diverse populations. Additionally, high-accuracy reads from 73 individuals uncovered an intriguing pattern of elevated TVR haplotype diversity among individuals of African descent.
This diversity was accompanied by extensive interchromosomal sharing and duplication of TVR architectures, highlighting the complex interplay of telomere variation within and between populations.
The researchers also conducted a focused investigation on subtelomeric TAR1 elements, finding a strong association between these elements and local DNA methylation patterns, as well as telomere motif diversity. These findings collectively paint a comprehensive multidimensional atlas of telomere diversity across a range of biological scales, shedding light on how telomere architecture varies and is inherited in different species, chromosome ends, haplotypes, and populations.
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