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Deciphering the ontogeny of unmutated and mutated subsets of Chronic Lymphocytic Leukemia
University of Skövde, School of Bioscience.
2019 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

Chronic Lymphocytic Leukemia (CLL) is a type of cancer that affects the B cells of the immune system causing problems in the process of producing antibodies. It can be sorted into mutated and unmutated CLL based on the percentage of somatic mutations in the Immunoglobulin Heavy chain Variable region (IgHV). The B cells of healthy individuals can be sorted into three groups; CD27dull memory B cells (MBCs), CD27bright MBCs and naïve B cells. The hypothesis for the project was that the unmutated CLL subset originates from CD27dull MBCs and the mutated CLL subset originates from CD27bright MBCs. RNA-sequencing data from healthy individuals were acquired from a collaboration partner in Rome and CLL-patients were collected from public datasets available online. Several bioinformatic tools were used to analyze the data. First, the quality of the data files was checked, then adapter sequence from the sequencing process and low-quality bases were removed (trimming). Good quality of the files was confirmed after the trimming. Secondly, these files were mapped against the human reference genome (GRCh38/hg38) for alignment, then the resulted data was used to check for genes that showed differential expression between the different groups. Results were analyzed and visualized using Venn diagrams, Principal Component Analysis (PCA) and heatmap plots and random forest. A list of 85 genes was generated based on the different comparisons and was used in one PCA plot that showed clear separation between the different groups. The SWAP70 gene was analyzed for single nucleotide polymorphisms (SNPs). The study concluded five genes that could be used as biomarkers for CLL and the diagnosis of its subtypes where some of them were discussed in previous studies. Also, the mutated CLL subset showed a similar behavior to the healthy individuals and this could validate the original hypothesis and justifies the better disease prognosis for this subtype.

Place, publisher, year, edition, pages
2019. , p. 33
Keywords [en]
CLL, NGS, mutated CLL, unmutated CLL, CD27 bright, CD27 dull, memory B cell, RNA-sequencing
National Category
Bioinformatics and Systems Biology Immunology
Identifiers
URN: urn:nbn:se:his:diva-17286OAI: oai:DiVA.org:his-17286DiVA, id: diva2:1330079
External cooperation
University of Gothenburg
Subject / course
Systems Biology
Educational program
Molecular Biotechnology - Master's Programme, 120 ECTS
Supervisors
Examiners
Available from: 2019-06-26 Created: 2019-06-25 Last updated: 2019-06-26Bibliographically approved

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CiteExportLink to record
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