High-throughput single-molecule mapping links subtelomeric variants and long-range haplotypes with specific telomeres.
Accurate maps and DNA sequences for human subtelomere regions, along with detailed knowledge of subtelomere variation and long-range telomere-terminal haplotypes in individuals, are critical for understanding telomere function and its roles in human biology. Here, we use a highly automated whole genome mapping technology in nano-channel arrays to analyze large terminal human chromosome segments extending from chromosome-specific subtelomere sequences through subtelomeric repeat regions to terminal (TTAGGG)n repeat tracts. We establish detailed maps for subtelomere gap regions in the human reference sequence, detect many new large subtelomeric variants and demonstrate the feasibility of long-range haplotyping through segmentally duplicated subtelomere regions. These features make the method a uniquely valuable new tool for improving the quality of genome assemblies in complex DNA regions. Based on single molecule mapping of telomere-terminal DNA fragments, we provide proof of principle for a novel method to estimate telomere lengths linked to distinguishable telomeric haplotypes; this single-telomere genotyping method may ultimately enable delineation of human cis elements involved in telomere length regulation.
Drexel University, School of Biomedical Engineering, Philadelphia, PA, 19104 USA.
Eleanor
E
Young
Drexel University, School of Biomedical Engineering, Philadelphia, PA, 19104 USA.
Steven
S
Pastor
Drexel University, School of Biomedical Engineering, Philadelphia, PA, 19104 USA.
Ramakrishnan
R
Rajagopalan
Drexel University, School of Biomedical Engineering, Philadelphia, PA, 19104 USA.
Jennifer
J
McCaffrey
Drexel University, School of Biomedical Engineering, Philadelphia, PA, 19104 USA.
Justin
J
Sibert
Cardiovascular Research Institute, University of California, San Francisco, CA, 94158 USA.
Angel C Y
ACY
Mak
Cardiovascular Research Institute, University of California, San Francisco, CA, 94158 USA.
Pui-Yan
PY
Kwok
Old Dominion University, Medical Diagnostic and Translational Sciences, Norfolk, VA, 23529 USA.
Harold
H
Riethman
Drexel University, School of Biomedical Engineering, Philadelphia, PA, 19104 USA.|Institute of Molecular Medicine and Infectious Disease, School of Medicine, Drexel University, Philadelphia, PA, 19102 USA.
Ming
M
Xiao
D001331:Automation; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA; D005240:Feasibility Studies; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000235:genetics*
D004247:DNA