Overlooked: Extrachromosomal DNA and Their Possible Impact on Whole Genome Sequencing

ABSTRACT

Extrachromosomal (ec) DNA in eukaryotic cells has been known for decades. Thestructures described range from linear double stranded (ds) DNA to circular dsDNA, distinct frommitochondrial (mt) DNA. The sizes of circular forms are described from some hundred base pairs(bp) up to more than 150 kbp. The number of molecules per cell ranges from several hundred to athousand. Semi-quantitative determinations of circular dsDNA show proportions as high as severalpercentages of the total DNA per cell. These ecDNA fractions harbor sequences that are known tobe present in chromosomal DNA (chrDNA) too. Sequencing projects on, for example the humangenome, have to take into account the ecDNA sequences which are simultaneously ascertained;corrections cannot be performed retrospectively. Concerning the results of sequencings derivedfrom extracted whole DNA if the ecDNA fractions contained therein are not taken into account,erroneous conclusions at the chromosomal level may result.