{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T12:30:43Z","timestamp":1768221043890,"version":"3.49.0"},"reference-count":19,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Hospital of Leipzig"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Germline genetic testing plays a critical role in diagnosing inherited predispositions and increasingly guides therapeutic and surveillance choices\u2014but 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\u2014buccal swab, nail, and eyebrow follicles\u2014in 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 &lt; 0.01). Across methods, STR yielded on average \u22486 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 (\u224812\u201314 and 15\u201320 percentage points, respectively); longer times since hematopoietic stem cell transplantation correlated with lower levels for nail samples, and donor\u2013recipient sex match correlated with higher donor DNA (~7\u20138 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 (\u2265 5\u201310%) before comprehensive germline analysis, reducing the risk that chimeric donor DNA distorts germline variant interpretation.<\/jats:p>","DOI":"10.3390\/ijms27020744","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Who Am I? Eyebrow Follicles Minimize Donor-Derived DNA for Germline Testing After Hematopoietic Stem Cell Transplantation"],"prefix":"10.3390","volume":"27","author":[{"given":"Matthias","family":"Mertens","sequence":"first","affiliation":[{"name":"MIT Future Tech, MIT Sloan School of Business, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Sadlo","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rn-Sven","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-7490","authenticated-orcid":false,"given":"Klaus","family":"Metzeler","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louisa","family":"Zschenderlein","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanett","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Leipzig Medical Center, Institute of Legal Medicine, Leipzig University, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Thull","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine and University Hospital, University of Cologne, 50937 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mert","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine and University Hospital, University of Cologne, 50937 Cologne, Germany"},{"name":"Institute of Human Genetics, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3352-1035","authenticated-orcid":false,"given":"Clara","family":"Velmans","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine and University Hospital, University of Cologne, 50937 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Tumewu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"B\u00f6hme","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Kl\u00f6tzer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Weigert","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-285X","authenticated-orcid":false,"given":"Vladan","family":"Vucinic","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-1424","authenticated-orcid":false,"given":"Julia","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4014-8173","authenticated-orcid":false,"given":"Mareike","family":"Mertens","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Boston Children\u2019s Hospital, Harvard Medical 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