In their study, Wickland et al. (1) reported finding lower exome sequencing coverage among ancestrally African patients in The Cancer Genome Atlas. For 3 cancer types, the lower sequencing coverage could not be explained by lower sequencing depth. The authors therefore attributed the lower sequencing coverage to a “known European bias in the human reference genome” that affected exome capture kit design. We question that inference. The human reference genome was derived mainly from 8 anonymized volunteers in 1997 from Buffalo, NY, USA (2). However, the Buffalo population is not, as the authors stated, “almost all European.” The most recent US Census lists the population as 35% Black or African American (3). Moreover, the ancestral composition of the human reference genome has previously been studied (4,5). Notably, approximately 70% of the human reference genome was derived from a single male volunteer (library RPCI-11) (2). That individual has approximately 50% genetic ancestry each from sub-Saharan Africa and Europe, consistent with being an African American (4,5). Thus, any European bias of the reference genome would be substantially less than supposed (though might still account for some of the authors’ findings). Twenty years after the completion of the Human Genome Project, the sizable African makeup of the human reference genome remains widely unrecognized. Although African genomes are still underrepresented in biomedical studies and databases (6), the Human Genome Project at least partially succeeded in mirroring human population diversity.
Funding
R.M. was funded by a Stanford Vice Provost for Undergraduate Education undergraduate research grant, and J.R.P. was funded by a Stanford Introductory Seminars teaching stipend.
Notes
Role of the funder: The funders had no role in writing this correspondence or the decision to submit it for publication.
Disclosures: The authors declare that they have no competing interests.
Author contributions: R.M. and J.R.P.: writing—original draft, writing—review & editing.
Contributor Information
Rhea Mitr, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Jonathan R Pollack, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Data Availability
There are no supporting datasets, computer code, or software tools associated with this correspondence.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
There are no supporting datasets, computer code, or software tools associated with this correspondence.