Differential Replication Leads to Copy Number Variation and Genome Rearrangements of Polyploid Cells

Polyploid;not listed

Yarosh, William HenryHattar, Samer ;

Johns Hopkins University

关键词: Polyploid;    not listed;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39327/YAROSH-DISSERTATION-2014.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Although polyploidy is pervasive throughout nature, itsfunction is still debated. It can arise through multiplemechanisms; one mechanism is the endocycle, a modified cellcycle where the genome is replicated, but mitosis does notoccur. An endocycle does not require that the genomereplicate completely. This can result in a phenomena knownas under replication and results in copy number variationof the genome. In addition to copy number variation, itresults in different genomic structure; however thisstructure is not known and there are multiple modelsdescribing the potential structures arising from underreplication. One model assumes that the free ended DNAresulting from under replication are not resolved,resulting in a DNA net. Another model assumes that freeended DNA are resolved resulting in genomic rearrangementsas the free ends are connected to each other, resulting inparallel strands of DNA of different sequences and length.This study uses paired end reverse terminator sequencing tomeasure copy number variation as well as identify genomicrearrangements in order to determine which regions of thegenome under replicate and the structure of an underreplicated genome in multiple polyploid cell types. Theunder replicating regions of the genome contain similariiitypes of chromatin, genes with similar function, and randomrearrangements within these regions to resolve free ends ofthe DNA resulting from incomplete DNA replication. Thesefindings provide insights into the function of copy numbervariation, and answer the question of the structure of thegenome resulting from under replication. In addition, theysuggest that genomic rearrangements could result inadditional gene diversity or reprogram the expression ofexisting genes.