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Related Experiment Video
Updated: Sep 28, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A complete reference genome improves analysis of human genetic variation.
Sergey Aganezov1, Stephanie M Yan2, Daniela C Soto3
1Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
The new Telomere-to-Telomere CHM13 genome reference significantly improves human genetic analysis by adding sequence, correcting errors, and enhancing variant discovery. This advanced reference is poised to supersede GRCh38 for human genetics research.
Area of Science:
- Genomics
- Human Genetics
Background:
- The human genome reference is crucial for genetic studies.
- Previous references had limitations in complex and repetitive regions.
Purpose of the Study:
- To introduce and evaluate the Telomere-to-Telomere CHM13 (T2T-CHM13) genome reference.
- To demonstrate its improvements over existing references like GRCh38.
Main Methods:
- The T2T-CHM13 genome assembly was generated.
- Read mapping and variant calling were performed using T2T-CHM13 on diverse human samples.
- Performance was compared against the GRCh38 reference.
Main Results:
- T2T-CHM13 adds ~200 million base pairs and corrects thousands of structural errors.
- It universally improves read mapping and variant calling across diverse samples.
- Hundreds of thousands of new variants were identified in previously unresolved regions.
- Spurious variants, including false positives in medically relevant genes, were significantly reduced.
Conclusions:
- The T2T-CHM13 reference enhances variant discovery and accuracy in human genetics.
- It unlocks complex genomic regions for clinical and functional studies.
- T2T-CHM13 is positioned to replace GRCh38 as the standard human reference genome.

