Who Am I? Eyebrow Follicles Minimize Donor-Derived DNA for Germline Testing After Hematopoietic Stem Cell Transplantation
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ijms-27-00744.pdf
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Author(s)
Mertens, Matthias
Sadlo, Mona
Kühl, Jörn-Sven
Metzeler, Klaus
Zschenderlein, Louisa
Edelmann, Jeanett
Lehmann, Claudia
Thull, Sarah
Karakaya, Mert
Velmans, Clara
Date Issued
January 11, 2026
Journal
International Journal of Molecular Sciences
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Mertens, M.; Sadlo, M.; Kühl, J.-S.; Metzeler, K.; Zschenderlein, L.; Edelmann, J.; Lehmann, C.; Thull, S.; Karakaya, M.; Velmans, C.; et al. Who Am I? Eyebrow Follicles Minimize Donor-Derived DNA for Germline Testing After Hematopoietic Stem Cell Transplantation. Int. J. Mol. Sci. 2026, 27, 744.
Version
Final published version
Abstract
Germline genetic testing plays a critical role in diagnosing inherited predispositions and increasingly guides therapeutic and surveillance choices—but becomes technically challenging after allogeneic hematopoietic stem cell transplantation (HSCT), when donor-derived DNA contaminates host tissues. To address this, we compared donor-derived DNA across three accessible tissues—buccal swab, nail, and eyebrow follicles—in recipients after hematopoietic stem cell transplantation using two orthogonal assays (34-SNP next-generation sequencing and a 27-marker short tandem repeat panel) and modeled clinical covariates that influence chimerism. Eyebrow follicles showed consistently low donor DNA (median 1% by NGS; 3% by STR) whereas buccal swabs and nails carried substantially higher donor fractions (+25 and +22 percentage points versus eyebrow, respectively; both p < 0.01). Across methods, STR yielded on average ≈6 percentage points higher donor fractions than NGS at low-level chimerism. Several transplant covariates correlated with chimerism: matched-related donors and a perfect HLA match (10/10) were each associated with lower donor DNA (≈12–14 and 15–20 percentage points, respectively); longer times since hematopoietic stem cell transplantation correlated with lower levels for nail samples, and donor–recipient sex match correlated with higher donor DNA (~7–8 percentage points). Even low-level chimerism can distort germline variant interpretation. We propose a pragmatic protocol for post-hematopoietic stem cell transplantation germline testing that prioritizes eyebrow follicles as the default tissue. An SNP-based quality control assay is used to flag unsafe donor fractions (≥ 5–10%) before comprehensive germline analysis, reducing the risk that chimeric donor DNA distorts germline variant interpretation.
MIT Department
Sloan School of Management
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DOI of Published Version
http://dx.doi.org/10.3390/ijms27020744
