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bioRxiv · 10.1101/2024.01.29.577739

Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modelling

Ryan, M.·McDonough, J. A.·Ward, M. E.·Cookson, M. R.·Skarnes, W. C.·Merkle, F. T.
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Abstract

Gracia-Diaz and colleagues analysed high-density DNA microarray and whole genome sequencing (WGS) data from the KOLF2.1J reference human induced pluripotent stem cell (hiPSC) line1, and report the presence of five high-confidence heterozygous copy number variants (CNVs) at least 100kbp in length2. Since three of these CNVs span coding genes, some of which have been associated with neurodevelopmental disease, the authors raise the concern that these CNVs may compromise the utility of KOLF2.1J for neurological disease modelling. We appreciate their thorough analysis and thoughtful interpretation, and agree that potential users of this line should be made aware of all cases where KOLF2.1J differs from the reference genome. However, we believe that the benefits from the widespread use of KOLF2.1J outweigh the potential risks that might arise from the identified CNVs.

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Ryan, M., McDonough, J. A., Ward, M. E., Cookson, M. R., Skarnes, W. C., Merkle, F. T.. 2024-01-29. Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modelling. https://doi.org/10.1101/2024.01.29.577739

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