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Full-Text Articles in Medical Genetics
Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao
Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao
Theses and Dissertations (ETD)
Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …
Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson
Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson
Theses and Dissertations (ETD)
Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …
Revealing A Non-Canonical Role Of Anti-Apoptotic Mcl-1 In Early Embryonic Development, Xue Yang
Revealing A Non-Canonical Role Of Anti-Apoptotic Mcl-1 In Early Embryonic Development, Xue Yang
Theses and Dissertations (ETD)
MCL-1, a well-known pro-survival BCL-2 family member, is indispensable for the survival of various cellular lineages and is also among the most frequently amplified genes in a variety of human malignancies. Gene ablation studies previously revealed that Mcl-1 deficiency leads to embryonic lethality around E3.5 during peri-implantation stage. Strikingly, the study did not detect any increase in apoptotic cells of the blastocyst, indicating a function of MCL-1 beyond regulating apoptosis. Our previous studies revealed an unrecognized role of MCL-1 in promoting mitochondrial physiology, which is independent of its classical anti-apoptotic function and requires being imported into the mitochondrial matrix. In …
Functional Analysis Of Genomic Variation And Impact On Molecular And Higher Order Phenotypes, Ashutosh Kumar Pandey
Functional Analysis Of Genomic Variation And Impact On Molecular And Higher Order Phenotypes, Ashutosh Kumar Pandey
Theses and Dissertations (ETD)
Reverse genetics methods, particularly the production of gene knockouts and knockins, have revolutionized the understanding of gene function. High throughput sequencing now makes it practical to exploit reverse genetics to simultaneously study functions of thousands of normal sequence variants and spontaneous mutations that segregate in intercross and backcross progeny generated by mating completely sequenced parental lines. To evaluate this new reverse genetic method we resequenced the genome of one of the oldest inbred strains of mice—DBA/2J—the father of the large family of BXD recombinant inbred strains. We analyzed ~100X wholegenome sequence data for the DBA/2J strain, relative to C57BL/6J, the …