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Alternative Splicing of Human, Rat and Mouse Gel-Forming Mucin Genes as Studied with Bioinformatics Tools
Bibliografi
Author:
Markarian, Eric
Topik:
mucin genes
;
mucin proteins
;
cancer
;
mRNAs
;
bioinformatics tools
;
human
;
rat
;
mouse
Bahasa:
(EN )
Penerbit:
International Masters Program in Bioinformatics Chalmers University of Technology
Tempat Terbit:
Göteborg
Tahun Terbit:
2007
Jenis:
Theses - Master Thesis
Fulltext:
4_Alternative splicing of human, rat and mouse gel-forming mucin genes as studied with bioinformatics tools.pdf
(881.96KB;
8 download
)
Abstract
Mechanisms acting during expression of mucin genes can produce mucin proteins that are involved in inflammatory diseases and cancer. One important mechanism is alternative splicing that produces several mRNAs using one pre-mRNA as a starting point. The aim of this work was to predict mucin transcripts/proteins that are products of alternative splicing. Four gel-forming mucin proteins (MUC2, MUC5AC, MUC5B and MUC6) from human, mouse and rat that normally protect the epithelial surfaces in the body were studied in detail at DNA, mRNA, EST and protein levels with different bioinformatics tools. The objective was to identify as many candidate splice variants as possible that could be verified and further examined using wet laboratory experiments. Genes of interest were identified using BLAT searches in the UCSC Genome Browser. We made use of precompiled EST alignments to genomic sequences that were available in that browser. Such alignments were inspected to identify potential splice variants.
In the case of the human mucin MUC2, three ESTs were identified likely to correspond to splicing variants. One of them gave rise to a protein that is shorter than the original protein, whereas the other two gave rise to proteins that lack internal portions of the protein of six and seventy-seven amino acids, respectively. For human MUC5AC there was no evidence of alternative splicing but for MUC5B, two alternative splicing candidates were observed. One of these gave an alternative protein shorter than the original one whereas the other resulted in a protein with a long C-terminal part different from the normal protein. Finally, a MUC6 splicing variant was identified, corresponding to a protein shorter than the normal protein. The alternative splicing candidates were evaluated using profiles for 5’ and 3’ splice sites. The 5’ splice site of the MUC2 variant that lacked six amino acids scored very high as well as the 3’ splice site of the MUC6 splice form. Finally, both 5’ and 3’ splice sites of the MUC5B with a different C-terminal scored high.
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