Biology subjects

Groot, A.

Publications and source records attributed to Groot, A..

3 recordsLinked to original sources

bioRxiv2026

Nanopore sequencing to measure chromosome end-specific telomere lengths in human cells

Summary/AbstractTelomere length has a significant impact on human health. Short telomeres cause age-related diseases, including pulmonary fibrosis, immunodeficiency, and bone marrow failure, while long telomeres predispose to cancer. Given the impact on human health, accurately measuring telomere length is important. A variety of methods have been developed over the past 40 years to measure telomere length. Many of these methods report only on the mean length of all of the telomere in the cell. Here, we describe the Telomere Profiling protocol using Oxford Nanopore Technologies (ONT) based on long read sequencing that can accurately measure chromosome specific telomere length.

genomics↗

bioRxiv2025

Complete genomes of a multi-generational pedigree to expand studies of genetic and epigenetic inheritance

Pedigree analysis remains the gold standard for rare disease diagnostics, yet whole genome sequencing studies typically omit critical regions like centromeres, telomeres, and acrocentric chromosome p-arms. Here, we present telomere-to-telomere (T2T) reference genomes for four self-identified African American individuals of admixed ancestry spanning three generations. Our parent-of-origin assigned, chromosome-level assemblies revealed precise meiotic recombination breakpoints in previously inaccessible regions, including recombination events across acrocentric and subtelomeric sequences. Centromeric regions were highly stable, with multi-megabase arrays inherited intact across three generations, while the position of kinetochore assembly sites remained consistent and predominantly associated with the p-arm proximal region. The relative lengths of telomeres on individual chromosomes were maintained across generations. Using a targeted rDNA assembly approach, we reconstructed a complete megabase-scale ribosomal DNA (rDNA) array corresponding to the paternal chromosome 14. This openly available pedigree provides a benchmark dataset for studying recombination and genetic and epigenetic variation across the complete genome.

genomics↗

bioRxiv2023

Human telomere length is chromosome specific and conserved across individuals

Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. To probe these mechanisms, we developed a nanopore sequencing method, Telomere Profiling, that is easy to implement, precise, and cost effective with broad applications in research and the clinic. We sequenced telomeres from individuals with short telomere syndromes and found similar telomere lengths to the clinical FlowFISH assay. We mapped telomere reads to specific chromosome end and identified both chromosome end-specific and haplotype-specific telomere length distributions. In the T2T HG002 genome, where the average telomere length is 5kb, we found a remarkable 6kb difference in lengths between some telomeres. Further, we found that specific chromosome ends were consistently shorter or longer than the average length across 147 individuals. The presence of conserved chromosome end-specific telomere lengths suggests there are new paradigms in telomere biology that are yet to be explored. Understanding the mechanisms regulating length will allow deeper insights into telomere biology that can lead to new approaches to disease.

molecular biology↗