Related Experiment Video
Updated: Oct 6, 2025

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
Published on: September 15, 2021
Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence
Christopher A Miller1, Jason R Walker2, Travis L Jensen3
1Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Abstract:
The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue.
Related Concept Videos
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Translation
Translation Produces the Building Blocks of Life
Proteins are...
Leaky Scanning
Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Point and Frameshift Mutations
Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

