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Circular DNA elements of chromosomal origin are common in healthy human somatic tissue

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  • Henrik Devitt Møller
  • Marghoob Mohiyuddin
  • Iñigo Prada-Luengo
  • M. Reza Sailani
  • Jens Frey Halling
  • Peter Plomgaard
  • Lasse Maretty
  • Anders Johannes Hansen
  • Michael P. Snyder
  • Henriette Pilegaard
  • Hugo Y.K. Lam
  • Birgitte Regenberg
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The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). However, it must be expected that kb eccDNAs exist in normal cells as a result of mutations. Here, we purify and sequence eccDNAs from muscle and blood samples from 16 healthy men, detecting ~100,000 unique eccDNA types from 16 million nuclei. Half of these structures carry genes or gene fragments and the majority are smaller than 25 kb. Transcription from eccDNAs suggests that eccDNAs reside in nuclei and recurrence of certain eccDNAs in several individuals implies DNA circularization hotspots. Gene-rich chromosomes contribute to more eccDNAs per megabase and the most transcribed protein-coding gene in muscle, TTN (titin), provides the most eccDNAs per gene. Thus, somatic genomes are rich in chromosome-derived eccDNAs that may influence phenotypes through altered gene copy numbers and transcription of full-length or truncated genes.

Original languageEnglish
JournalNature Communications
Volume9
Issue number1
Pages (from-to)1069
ISSN2041-1723
DOIs
Publication statusPublished - 1 Dec 2018

ID: 55633707