Single-cell sequencing: promises and challenges for human genetics

Varun K A Sreenivasan; Jana Henck; Malte Spielmann

doi:10.1515/medgen-2022-2156

Single-cell sequencing: promises and challenges for human genetics

Med Genet. 2022 Nov 29;34(4):261-273. doi: 10.1515/medgen-2022-2156. eCollection 2022 Dec.

Authors

Varun K A Sreenivasan¹, Jana Henck^{1

2}, Malte Spielmann^{1

2

3}

Affiliations

¹ Institute of Human Genetics, University Hospital Schleswig-Holstein, University of Lübeck and Kiel University, 23562 Lübeck, 24105 Kiel, Germany.
² Human Molecular Genomics Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany.
³ DZHK e. V. (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 23538 Lübeck, Germany.

Abstract

Over the last decade, single-cell sequencing has transformed many fields. It has enabled the unbiased molecular phenotyping of even whole organisms with unprecedented cellular resolution. In the field of human genetics, where the phenotypic consequences of genetic and epigenetic alterations are of central concern, this transformative technology promises to functionally annotate every region in the human genome and all possible variants within them at a massive scale. In this review aimed at the clinicians in human genetics, we describe the current status of the field of single-cell sequencing and its role for human genetics, including how the technology works as well as how it is being applied to characterize and monitor diseases, to develop human cell atlases, and to annotate the genome.

Keywords: CRISPR; cell atlas; cellular composition; diagnostics; disease characterization; human genetics; phenotyping; saturation gene editing; single-cell sequencing; therapy.

Grants and funding

M.S. is a DZHK principal investigator and is supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (SP1532/3-1, SP1532/4-1, and SP1532/5-1) and the Deutsches Zentrum für Luft- und Raumfahrt (DLR 01GM1925).