Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence

Christopher A. Miller; Jason R. Walker; Travis L. Jensen; William F. Hooper; Robert S. Fulton; Jeffrey S. Painter; Mikkael A. Sekeres; Timothy J. Ley; David H. Spencer; Johannes B. Goll; Matthew J. Walter

doi:10.1016/j.jmoldx.2021.10.013

Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence

Christopher A. Miller, Jason R. Walker, Travis L. Jensen, William F. Hooper, Robert S. Fulton, Jeffrey S. Painter, Mikkael A. Sekeres, Timothy J. Ley, David H. Spencer, Johannes B. Goll, Matthew J. Walter

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Pages (from-to)	219-223
Number of pages	5
Journal	Journal of Molecular Diagnostics
Volume	24
Issue number	3
DOIs	https://doi.org/10.1016/j.jmoldx.2021.10.013
State	Published - Mar 2022

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10.1016/j.jmoldx.2021.10.013

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title = "Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence",

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.",

author = "Miller, {Christopher A.} and Walker, {Jason R.} and Jensen, {Travis L.} and Hooper, {William F.} and Fulton, {Robert S.} and Painter, {Jeffrey S.} and Sekeres, {Mikkael A.} and Ley, {Timothy J.} and Spencer, {David H.} and Goll, {Johannes B.} and Walter, {Matthew J.}",

note = "Publisher Copyright: {\textcopyright} 2022 Association for Molecular Pathology and American Society for Investigative Pathology",

year = "2022",

month = mar,

doi = "10.1016/j.jmoldx.2021.10.013",

language = "English",

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T1 - Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence

AU - Miller, Christopher A.

AU - Walker, Jason R.

AU - Jensen, Travis L.

AU - Hooper, William F.

AU - Fulton, Robert S.

AU - Painter, Jeffrey S.

AU - Sekeres, Mikkael A.

AU - Ley, Timothy J.

AU - Spencer, David H.

AU - Goll, Johannes B.

AU - Walter, Matthew J.

PY - 2022/3

Y1 - 2022/3

N2 - 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.

AB - 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.

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AN - SCOPUS:85125527899

SN - 1525-1578

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SP - 219

EP - 223

JO - Journal of Molecular Diagnostics

JF - Journal of Molecular Diagnostics

IS - 3

ER -

Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence

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