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Analysis of a clonal repertoire containing insertions and deletions
Thesis   Open access

Analysis of a clonal repertoire containing insertions and deletions

Adam David Still
Master of Science (M.S.), Drexel University
Jan 2018
DOI:
https://doi.org/10.17918/D8FT0Q
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Abstract

B cells Bioinformatics Biomedical Engineering
In my thesis I sought to characterize the patterns of somatic insertions and deletions in B cell receptor genes in the healthy immune repertoire of B cell clones. B-cells can produce a highly diverse array of B-cell receptors (BCRs) to respond to a nearly infinite number of foreign antigens. This diversity is thought to be generated in two main steps: V(D)J recombination and somatic point mutations. I wanted to see if insertions or deletions of multiple nucleotide segments were also involved in enhancing the diversity of the B-cell repertoire. To do so I compared the incidence, size and distribution of in-frame indels that could be selected for or against and out of frame indels that we do not expect to make functional receptors. I found that in frame indels were focused in the variable regions of the V-segment (CDR1, CDR2, HV4) while those indels which produced out of frame BCRs were randomly distributed. The in-frame indel clones were largely between 1 amino acid and 3 amino acids in length. Out of frame indels were mostly of single to four nucleotides in length. Finally, germline diversity of specific amino acid positions was strongly and significantly correlated to the number of in-frame indel events at that position but not to the number of out of frame indels. The categorical difference in the placement and size of in-frame indels compared to out of frame indels, their correlation to germline diversity and the incidence of some not whole-amino acid length indels that saved CDR3 out of frame clones and expanded, imply indels can influence and enhance the diversification process of functional B cell clones.

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