Gutenberg Open Science: RDA coupled with deep sequencing detects somatic SVA-retrotranspositions and mosaicism in the human brain

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9146

Full metadata record

DC Field	Value	Language
dc.contributor.author	Möhner, Jonas	-
dc.contributor.author	Scheuren, Maurice	-
dc.contributor.author	Woronzow, Valentina	-
dc.contributor.author	Schumann, Sven	-
dc.contributor.author	Zischler, Hans	-
dc.date.accessioned	2023-06-02T09:15:06Z	-
dc.date.available	2023-06-02T09:15:06Z	-
dc.date.issued	2023	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/9163	-
dc.description.abstract	Cells of the developing human brain are affected by the progressive acquisition of genetic and epigenetic alterations that have been reported to contribute to somatic mosaicism in the adult brain and are increasingly considered a possible cause of neurogenetic disorders. A recent work uncovered that the copy–paste transposable element (TE) LINE-1 (L1) is mobilized during brain development, and thus mobile non-autonomous TEs like AluY and SINE-VNTR-Alu (SVA) families can use L1 activity in trans, leading to de novo insertions that may influence the variability of neural cells at genetic and epigenetic levels. In contrast to SNPs and when considering substitutional sequence evolution, the presence or absence of TEs at orthologous loci represents highly informative clade markers that provide insights into the lineage relationships between neural cells and how the nervous system evolves in health and disease. SVAs, as the ‘youngest’ class of hominoid-specific retrotransposons preferentially found in gene- and GC-rich regions, are thought to differentially co-regulate nearby genes and exhibit a high mobility in the human germline. Therefore, we determined whether this is reflected in the somatic brain and used a subtractive and kinetic enrichment technique called representational difference analysis (RDA) coupled with deep sequencing to compare different brain regions with respect to de novo SINE-VNTR-Alu insertion patterns. As a result, we detected somatic de novo SVA integrations in all human brain regions analyzed, and the majority of de novo insertions can be attributed to lineages of telencephalon and metencephalon, since most of the examined integrations are unique to different brain regions under scrutiny. The SVA positions were used as presence/absence markers, forming informative sites that allowed us to create a maximum parsimony phylogeny of brain regions. Our results largely recapitulated the generally accepted evo-devo patterns and revealed chromosome-wide rates of de novo SVA reintegration targets and preferences for specific genomic regions, e.g., GC- and TE-rich regions as well as close proximity to genes that tend to fall into neural-specific Gene Ontology pathways. We concluded that de novo SVA insertions occur in the germline and somatic brain cells at similar target regions, suggesting that similar retrotransposition modes are effective in the germline and soma.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	500 Naturwissenschaften	de_DE
dc.subject.ddc	500 Natural sciences and mathematics	en_GB
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.title	RDA coupled with deep sequencing detects somatic SVA-retrotranspositions and mosaicism in the human brain	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-9146	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 10 Biologie	de
jgu.organisation.number	7970	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Frontiers in cell and developmental biology	de
jgu.journal.volume	11	de
jgu.pages.alternative	1201258	de
jgu.publisher.year	2023	-
jgu.publisher.name	Frontiers Media	de
jgu.publisher.place	Lausanne	de
jgu.publisher.issn	2296-634X	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	500	de
jgu.subject.ddccode	570	de
jgu.publisher.doi	10.3389/fcell.2023.1201258	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

Files in This Item:

	File	Description	Size	Format
	rda_coupled_with_deep_sequenc-20230601120118114.pdf		2.22 MB	Adobe PDF	View/Open

Show simple item record