Quantitative assessment reveals the dominance of duplicated sequences in germline-derived extrachromosomal circular DNA

Abstract

Extrachromosomal circular DNA (eccDNA) plays a role in human diseases such as cancer, but little is known about the impact of eccDNA in healthy human biology. Since eccDNA is a tiny fraction of nuclear DNA, artificial amplification has been employed to increase eccDNA amounts, resulting in the loss of native compositions. We developed an approach to enrich eccDNA populations at the native state (naïve small circular DNA, nscDNA) and investigated their origins in the human genome. We found that, in human sperm, the vast majority of nscDNA came from high-copy genomic regions, including the most variable regions between individuals. Because eccDNA can be incorporated back into chromosomes, eccDNA may promote human genetic variation.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 17, 2021
Source ID
10.1073/pnas.2102842118

Entities

People

  • Anna Malkova
  • Armando E. Giuliano
  • Arvis Sulovari
  • Beth Osia
  • Evan E. Eichler
  • Hisashi Tanaka
  • Lila Mouakkad
  • Makoto Katsumata
  • Michael Murata
  • Ryusuke Suzuki

Organizations

  • Cedars-Sinai Medical Center
  • National Cancer Institute
  • United States Department of Defense
  • University of Iowa
  • University of Washington

Tags

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Oncology
  • Underwater engineering and Marine Technology.

Technology Areas

  • Biotechnology