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DNA sequence controls expression of gene involved in cancer

DNA sequence controls expression of gene involved in cancer. How Bioinformatics help. Group III Xia Yun, Zhao Liqun, Deng Yiyu , Ling Hui , Zhang Wei and Yu Faxing  . Cancer. Oncogene---A modified gene that increases the malignancy of a tumor cell

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DNA sequence controls expression of gene involved in cancer

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  1. DNA sequence controls expression of gene involved in cancer How Bioinformatics help Group III Xia Yun, Zhao Liqun, Deng Yiyu , Ling Hui , Zhang Wei and Yu Faxing 

  2. Cancer Oncogene---A modified gene that increases the malignancy of a tumor cell Proto-oncogene---A normal gene that can become an oncogene, either after mutation or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation

  3. Bcl-2 • B-cell lymphoma/leukemia-2. • Bcl-2 is the prototype for a family of mammalian genes govern mitochondrial membrane permeabilization, which is important for regulation of Apoptosis • The Bcl-2 gene is a proto-oncogene, it has been implicated in a number of cancers, including breast cancer, prostate cancer and lung carcinomas etc.

  4. The level of Bcl-2 should be tightly controlled

  5. Gene regulation Transcription RNA splicing RNA transport Translation RNA stability Post-translational

  6. Scientists have discovered a DNA sequence that causes the destabilization, and hence decay, of the proto-oncogene bcl-2 (B-cell lymphoma/leukemia-2).…… CA repeats in the 3’-untranslated region of bcl-2 mRNA mediate constitutively decay of bcl-2 mRNA To show the power of bioinformatics in scientific research!!!

  7. Bioinformatics Bioinformatics involves the use of techniques from applied mathematics, informatics, statistics, and computer science to solve biological problems. Bioinformatics makes use of mathematical tools to extract useful information from noisy data produced by high-throughput biological techniques such as genomics. Major research efforts in the field include sequence alignment, genome assembly, protein structure prediction, prediction of gene expression and protein-protein interactions, and the modeling of evolution etc.

  8. How can we find bibliographic information and full text articles?

  9. How can we find the Bcl-2 gene? Accession: M13994

  10. DNA sequence and protein sequence • atggcgcacg ctgggagaac ggggtacgac aaccgggaga tagtgatgaa gtacatccat tataagctgt cgcagagggg ctacgagtgg gatgcgggag atgtgggcgc cgcgcccccg ggggccgccc ccgcaccggg catcttctcc tcccagcccg ggcacacgcc ccatccagcc gcatcccgcg acccggtcgc caggacctcg ccgctgcaga ccccggctgc ccccggcgcc gccgcggggc ctgcgctcag cccggtgcca cctgtggtcc acctggccct ccgccaagcc ggcgacgact tctcccgccg ctaccgcggc gacttcgccg agatgtccag ccagctgcac ctgacgccct tcaccgcgcg gggacgcttt gccacggtgg tggaggagct cttcagggac ggggtgaact gggggaggat tgtggccttc tttgagttcg gtggggtcat gtgtgtggag agcgtcaacc gggagatgtc gcccctggtg gacaacatcg ccctgtggat gactgagtac ctgaaccggc acctgcacac ctggatccag gataacggag gctgggatgc ctttgtggaa ctgtacggcc ccagcatgcg gcctctgttt gatttctcct ggctgtctct gaagactctg ctcagtttgg ccctggtggg agcttgcatc accctgggtg cctatctgag ccacaagtga • MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPAASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLALRQAGDDFSRRYRGDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVE

  11. PDB Swiss

  12. How can you clone this gene using PCR and bioinformatics? • PCR primer design • Oligo • DNA star • Vector NTI 5’-UTR CDS 3’-UTR RES Digestion (PCR product/Vector) Ligation (Insert+Vector) Expression Vector

  13. How do you identify restriction endonuclease sites on this gene? • Webcutter • >gi|179366:1459-2178 Human B-cell leukemia/lymphoma 2 (bcl-2) proto-oncogene mRNA encoding bcl-2-alpha protein, complete cds ATGGCGCACGCTGGGAGAACGGGGTACGACAACCGGGAGATAGTGATGAAGTACATCCATTATAAGCTGT CGCAGAGGGGCTACGAGTGGGATGCGGGAGATGTGGGCGCCGCGCCCCCGGGGGCCGCCCCCGCACCGGG CATCTTCTCCTCCCAGCCCGGGCACACGCCCCATCCAGCCGCATCCCGCGACCCGGTCGCCAGGACCTCG CCGCTGCAGACCCCGGCTGCCCCCGGCGCCGCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCC ACCTGGCCCTCCGCCAAGCCGGCGACGACTTCTCCCGCCGCTACCGCGGCGACTTCGCCGAGATGTCCAG CCAGCTGCACCTGACGCCCTTCACCGCGCGGGGACGCTTTGCCACGGTGGTGGAGGAGCTCTTCAGGGAC GGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGTGTGTGGAGAGCGTCAACC GGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGATGACTGAGTACCTGAACCGGCACCTGCACAC CTGGATCCAGGATAACGGAGGCTGGGATGCCTTTGTGGAACTGTACGGCCCCAGCATGCGGCCTCTGTTT GATTTCTCCTGGCTGTCTCTGAAGACTCTGCTCAGTTTGGCCCTGGTGGGAGCTTGCATCACCCTGGGTG CCTATCTGAGCCACAAGTGA

  14. How would you find out what functional domains are present in Bcl-2?

  15. Functional domains of Bcl-2 Predicted by SMART

  16. How does one identify the ARE regions or the CAR region? • The AU-rich elements (AREs) mediate the rapid turnover of mRNAs encoding proteins that regulate cellular growth and body response to exogenous agents. • http://rc.kfshrc.edu.sa/ared/ The ARE-mRNA database (ARED) reveals that ARE-mRNAs encodes a wide repertoire of functionally diverse proteins belonging to different biological processes and important in disease states.

  17. How does one identify the ARE regions or the CAR region? ARE: AU rich CAR: CA rich Simple Plotcalculates DNA sequence composition using a sliding window that moves along the sequence at 1 base pair intervals 2281 ttaagaaaaa ataacacaca tataaacatc acacacacag acagacacac acacacacaa 2341 caattaacag tcttcaggca aaacgtcgaa tcagctattt actgccaaag ggaaatatca 2401 tttatttttt acattattaa gaaaaaagat ttatttattt aagacagtcc catcaaaact 2461 ccgtctttgg aaatccgacc actaattgcc aaacaccgct tcgtgtggct ccacctggat 2521 gttctgtgcc tgtaaacata gattcgcttt ccatgttgtt ggccggatca ccatctgaag

  18. Which organisms has Bcl-2 been found in?

  19. Nucleotide Nucleotide BLAST

  20. Genome Browser

  21. Searching in • BCL2_BOVIN (O02718) • Apoptosis regulator Bcl-2. {GENE: Name=BCL2} - Bos taurus (Bovine) • BCL2_CHICK (Q00709) • Apoptosis regulator Bcl-2. {GENE: Name=BCL2; Synonyms=BCL-2} - Gallus gallus (Chicken) • BCL2_CRIGR (Q9JJV8) • Apoptosis regulator Bcl-2. {GENE: Name=BCL2} - Cricetulus griseus (Chinese hamster) • BCL2_HUMAN (P10415) • Apoptosis regulator Bcl-2. {GENE: Name=BCL2} - Homo sapiens (Human) • BCL2_MOUSE (P10417) • Apoptosis regulator Bcl-2. {GENE: Name=Bcl2; Synonyms=Bcl-2} - Mus musculus (Mouse) • BCL2_RAT (P49950) • Apoptosis regulator Bcl-2. {GENE: Name=Bcl2; Synonyms=Bcl-2} - Rattus norvegicus (Rat)

  22. Protein sequences DNA sequence Functional domain Literature Search Restriction enzyme digestion Bioinformatics Homologous in other Organisms Primer design Predict feature region of DNA

  23. Future Work • Identify regulators of CAR Conjugate the CA-rich region to biotin, and apply the biotin-tagged CAR to biotin affinity column. Regulators binding to CAR will be captured by the column. Gel shifting indicates the binding between CAR and certain regulators, which can be identified by MS. • Set up a CAR database The CAR database can be set up by cytoscape under Linux system. This database will include information of CARs regulating different mRNA in different organisms

  24. Thank you

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