In this study a family of endogenous retroviruses, HERV-K(HML-2) was investigated. The family is
the youngest endogenous retrovirus family known in humans, with some of its members being
insertionally polymorphic in modern human populations. There have been numerous reports of
HERV-K(HML-2) members being present in cancer samples. Here, a robust analysis of the state of
HERV-K(HML-2) family in the human genome known to date is presented, along with the most
complete database of known insertions, present in modern human genomes. In addition to
literature data, 10 novel solo-LTR elements and 2 novel full-length truncated elements, found in
recent assemblies of the Human reference genome are reported in this study. Furthermore, a
bioinformatics pipeline used to detect HERV-K(HML-2) loci in genomic sequence data is presented.
The pipeline is used to analyze a large dataset of 11 different cancer sequencing projects coming
from The Cancer Genome Atlas, resulting in detection of 28 polymorphic insertions. 7 of these are
thought to be completely novel, whereas 10 display significance in occurrence rate when comparing
the cancer data to general population. A number of biochemical pathways suspected to be altered
by the detected insertions were found. Nevertheless, the low frequency of occurrence for novel
HERV-K(HML2) insertions detected in this study, combined with absence of novel insertions
detected in cancer tissue only suggest, that the hypothesis of HERV-K(HML-2) elements being still
active in modern human populations is unlikely. However, significant presence of unfixed insertions
in cancer samples combined with a list of genes known to be altered in cancer and influenced by
these loci suggest, that presence of these particular loci could influence cancer development and
Permanent link to this resource: https://doi.org/10.24384/rhs9-1z27
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Supervisors: Kanda, Ravinder K; Brooks, Susan
Faculty of Health and Life SciencesDepartment of Biological and Medical Sciences
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