Department, and the National Science Foundation for their support. Lastly I'd like to thank my thesis committee for their insight and assistance in the completion of my research. iii ABSTRACT How asexual reproduction affects genome evolution, and how organisms that are ancestrally sexual alter their reproductive machinery upon becoming asexual are both central unanswered questions in evolutionary biology. While these questions have been addressed to some extent in organisms such as asexual clams, rotifers, ostracods, arthropods, and fungi, the most powerful and direct tests of how sex and its absence influence evolution requires direct comparisons between closely related and otherwise similar sexual and asexual taxa. Here, I quantify the rates and patterns of molecular evolution in the meiosis-specific genes Msh4, Msh5, and Spo11 in multiple sexual and asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail. Because asexual P. antipodarum reproduce apomictically (without recombination), genes used only for meiosis should be under relaxed selection relative to meiosis-specific genes in sexual P. antipodarum,allowing me to directly study how asexuality affects the evolution of meiosisspecific genes. Contrary to expectations under relaxed selection, I found no evidence that these meiosis-specific genes are degrading in asexual P. antipodarum; instead they display molecular patterns consistent with purifying selection. The presence of intact meiosis-specific genes in asexual P. antipodarum hints that the asexuals may maintain the ability to perform meiosis despite reproducing apomictically. Asexual meiotic capability suggests that some meiotic components may persist or acquire a new role in these asexuals.
iv PUBLIC ABSTRACTHow asexual reproduction affects genome evolution, and how ancestrally sexual organisms alter their reproductive machinery upon becoming asexual are central unanswered questions in evolutionary biology. While these questions have been addressed to some extent in different asexual species, the most powerful tests of how sex and its absence influence evolution requires direct comparisons between closely related and otherwise similar sexual and asexual taxa. I address these questions by studying the evolution of genes critical to sexual reproduction in sexual and asexual lineages of
The detection of recurrent chromosomal rearrangements in B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is critical for patient management decisions. We present a newly diagnosed case of BALL in a young adult with a cryptic KMT2A/AFF1 fusion that was unappreciable by conventional chromosome and fluorescence in situ hybridization (FISH) KMT2A break-apart probe studies. To further characterize this abnormality, a next-generation sequencing strategy, mate-pair sequencing (MPseq) was performed and characterized a cryptic, insertional rearrangement that created KMT2A/AFF1 gene fusion. This case highlights the superior precision and resolution capabilities of NGS when compared to traditional cytogenetic methodologies, including conventional chromosome and FISH studies.
Zinc-finger protein 384 (ZNF384) gene fusions with EP300 have recently been described as a recurrent fusion in B-cell acute lymphoblastic leukemia (B-ALL) with a good response to conventional chemotherapy, suggesting a favorable prognosis. Herein, we report on a female patient aged 12 years with uninformative conventional chromosome and B-ALL panel fluorescence in situ hybridization studies with chromosomal microarray showing multiple copy number gains, including relative gains in the ZNF384 (12p13.31) and EP300 (22q13.2) gene regions, suggesting a cryptic EP300/ZNF384 fusion. Ultimately, a next-generation sequencing assay, mate pair sequencing, was utilized to confirm EP300/ZNF384 fusion in this B-ALL clone, which may confer a favorable overall prognosis and potential targeted therapy.
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