GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328480/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328480GEOGSEfalseTelomere variant sequences encode a genetic blueprint for allele-specific telomere length (dataset 2)The ends of human chromosomes are capped by specialized nucleoprotein structures known as telomeres, which are essential for genome stability. Recent advances in long-read sequencing have enabled allele-specific telomere length measurements at nucleotide resolution, uncovering extreme heterogeneity in telomere length between alleles that is determined at birth and gradually shortens with age. The shortening over time makes steady-state telomere length in human somatic cells a promising biomarker for age-associated diseases. However, the mechanisms underlying allele-specific telomere maintenance and its stability remain poorly understood. Here, we developed a high-resolution workflow combining PacBio and Nanopore long-read sequencing platforms to map allele-specific telomere length in human blood samples as well as cultured cell lines. By tracing allele-specific telomeric sequence in family members across multiple generations, we show that the allele-specific telomeric variant sequences (TVSs) are heritable (with mean similarity score > 0.95) and underlie the extreme heterogeneity of telomere length between alleles. Continuous cell proliferation likely drives the slow but stochastic evolution of allele-specific TVSs distribution, resulting in asymmetry in telomere inheritance from father and mother (p-value = 2.354e-7). Targeted deletion of allele-specific TVSs using CRISPR-Cas9 resets telomere length, further confirming their causal role in the control of allele-specific telomere maintenance (p-value < 2e-6). These results indicated that TVSs encode a novel class of heritable genetic elements underlying the allele-specific telomere length.2026/07/10GSE328480GSM9684205GSM9684204GSM9684203GSM9684202GSM9684201GSM9684200GSM9684189GSM9684199GSM9684188GSM9684198GSM9684187GSM9684197GSM9684196GSM9684195GSM9684194GSM9684193GSM9684192GSM9684191GSM96841903467826167328480Homo sapiens