Heritable variant sequences within telomeres set allele-specific length
Telomere variant sequences dispersed along chromosome ends account for extreme length differences between paired chromosomes, according to a study published in Nature Communications. Researchers combined PacBio and Nanopore sequencing to map allele-specific telomere lengths in human blood samples and cultured cell lines. By tracing allele-specific telomeric sequences in family members across multiple generations, they showed that telomere variant sequences are heritable and underlie the extreme heterogeneity of telomere length between alleles. Continuous cell proliferation drives the slow but stochastic evolution of allele-specific telomere variant sequences. Targeted deletion of allele-specific telomere variant sequences using CRISPR-Cas9 reset telomere length, confirming their causal role in the control of allele-specific telomere maintenance.
The findings explain why chromosome pairs have widely different telomere lengths. They could refine biomarkers for age-associated diseases that rely on telomere length measurements.
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