Professional Documents
Culture Documents
Submitted by:
Md. Mohsin Uddin Howlader Roll no: 468 Session: 2010-11 Department Of Zoology Jahangirnagar University, Dhaka
Submssion date:
Gene Mutation
A gene mutation is a personal change in the DNA sequence that makes up a gene. Mutation range in size from a single DNA building block (DNA base) to a large segment of a chromosome.
Nonsense mutation A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however the altered DNA sequence prematurely signals the cell to stop building a protein.
Insertion An incertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result the protein made by the gene may not function properly.
Deletion A deletion changes the number of DNA Bases By Removing a piece of DNA.
Duplication A duplication consists of a piece of DNA that is abnormally copied one or more times
Point mutation The replacement base pair by another. This are two types: 1.Transitions: A purine(or a pyrimidine) replaced by another. 2.Transversion Replacement of a by a pyrimidine
Frameshift mutations This occur when one or more base pair are inserted in or detected from DNA, changing the genes leading frame.
Reapeat expansion Nucleotide repeats are short DNA sequence that repeated a number of times in a row. eg-Trinucleotide repeat is made 3 base pair sequences.
cardiovascular disease and various cancers, is bringing genetics into not only the medical mainstream, but also the public mainstream. Moreover, molecular methods are becoming important in the diagnosis and
classification of malignant disease, as well as in determining prognosis and monitoring response to therapy. This paper describes current methods of studying the changes that underlie inherited and acquired disease and concludes with discussion of a technique that is generating excitement while still in development, the use of DNA microarrays or chips.
group, have also been determined to encode proteins critical for DNA damage repair.
Cancer cells
Cancer cells are cells that grow and divide at an unregulated, quickened pace. Although cancer cells can be quite common in a person they are only malignant when the other cells (particularly natural killer cells) fail to recognize and/or destroy them. In the past a common belief was that cancer cells failed to be recognized and destroyed because of a weakness in the immune system. However, more recent research has shown that the failure to recognize cancer cells is caused by the lack of particular co-stimulated molecules that aid in the way antigens react with lymphocytes.
Lack Differentiation
Normal cells stop dividing when they become crowded because mitosis is inhibited when cells contact nearby cells. Cancer cells continue to divide and produce a mass of cells called a tumor.
Lack Anchorage Dependence
Normal cells stop dividing when they become crowded because mitosis is inhibited when cells contact nearby cells. Cancer cells continue to divide and produce a mass of cells called a tumor.
Ability to Penetrate the Lamina
The lamina is a noncellular barrier that is attached to cells that line the surfaces, internal cavities, and organs (epithelial tissue). Normally, cells cannot penetrate this barrier and therefore cannot invade neighboring tissues and organs.
Immune System
The immune system can recognize foreign cells and invaders (bacteria, viruses, etc.) because they have proteins and other structures that are different from the bodys "self" markers.
Angiogenesis
Tumors need a blood supply for food and oxygen. Cancer cells release growth factors that cause nearby blood vessels to produce branches that grow into the cancerous tissue.
Oncogenes
A gene that contributes to the production of a cancer. Oncogenes are generally mutated forms of normal cellular genes (proto-oncogenes). A gene capable, when activated, of transforming a cell. Oncogenes are found in the oncogenically activated state in retroviruses and transformed cells and in their normal non-oncogenically activated state in nontransformed cells in which they are called proto-oncogenes.
Classification
There are several systems for classifying oncogenes, but there is not yet a widely accepted standard. They are sometimes grouped both spatially (moving from outside the cell inwards) and chronologically (parallelling the "normal" process of signal transduction). There are several categories that are commonly used: Category Growth factors, or mitogens Examples c-Sis Cancers glioblastomas, fibrosarcomas, osteosarcomas, breast carcinomas, and Receptor tyrosine kinases melanomas epidermal growth factor Breast cancer, receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth gastrointestinal stromal tumours, non-small-cell lung cancer and pancreatic cancer transduce signals for cell growth and differentiation. Gene functions induces cell proliferation.
factor receptor Cytoplasmic tyrosine kinases (VEGFR), HER2/neu Src-family, Syk-ZAP70 family, and BTK family of tyrosine kinases, the Abl gene in CML - Philadelphia chromosome colorectal and breast cancers, melanomas, ovarian cancers, gastric cancers, head and neck cancers, pancreatice cancer, lung cancer, brain cancers, and blood Cytoplasmic Serine/threonine kinases and their regulatory subunits Raf kinase, and cyclindependent kinases (through overexpression). cancers malignant melanoma, papillary thyroid cancer, colorectal cancer, and ovarian cancer mediate the responses to, and the activation receptors of cell proliferation, migration, differentiation, and survival Involved in organism development, cell cycle regulation, cell proliferation, differentiation, cells survival, and Regulatory GTPases Ras protein adenocarcinomas of the pancreas and colon, thyroid tumors, and Transcription factors myc gene myeloid leukemia malignant T-cell lymphomas and acute myleoid leukemias, apoptosis involved in signalling a major pathway leading to cell proliferation. -They regulate transcription of genes that induce
cell proliferation.
retinoblastoma. Knudson observed that the age of onset of retinoblastoma followed 2nd order kinetics, implying that two independent genetic events were necessary. He recognized that this was consistent with a recessive mutation involving a single gene, but requiring biallelic mutation. Oncogene mutations, in contrast, generally involve a single allele because they are gain-of-function mutations. There are exceptions to the "two-hit" rule for tumor suppressors, such as certain mutations in the p53 gene product. p53
mutations can function as a "dominant negative", meaning that a mutated p53 protein can prevent the function of normal protein from the un-mutated allele. Other tumor-suppressor genes that are exceptions to the "two-hit" rule are those that exhibit haploinsufficiency for example PTCH in
medulloblastoma. An example of this is the p27Kip1 cell-cycle inhibitor, in which mutation of a single allele causes increased carcinogen susceptibility.
Functions
Tumor-suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both. The functions of tumor-suppressor proteins fall into several categories including the following:
1. Repression of genes that are essential for the continuing of the cell
cycle. If these genes are not expressed, the cell cycle does not continue, effectively inhibiting cell division.
2. Coupling the cell cycle to DNA damage. As long as there is damaged
DNA in the cell, it should not divide. If the damage can be repaired, the cell cycle can continue.
3. If the damage cannot be repaired, the cell should initiate apoptosis
(programmed cell death) to remove the threat it poses for the greater good of the organism.
dispersing, block loss of contact inhibition, and inhibit metastasis. These proteins are known as metastasis suppressors.
5. DNA repair proteins are usually classified as tumor suppressors as well,
as mutations in such their genes increase the risk of cancer, for example mutations in HNPCC, MEN1 and BRCA. Furthermore, increased mutation rate from decreased DNA repair leads to increased
Examples
The first tumor-suppressor protein discovered was the Retinoblastoma protein (pRb) in human retinoblastoma; however, recent evidence has also implicated pRb as a tumor-survival factor. Another important tumor suppressor is the p53 tumor-suppressor protein encoded by the TP53 gene. Homozygous loss of p53 is found in 70% of colon cancers, 3050% of breast cancers, and 50% of lung cancers. Mutated p53 is also involved in the pathophysiology of leukemias, lymphomas, sarcomas, and neurogenic tumors. Abnormalities of the p53 gene can be inherited in LiFraumeni syndrome (LFS), which increases the risk of developing various types of cancers.
PTEN acts by opposing the action of PI3K, which is essential for antiapoptotic, pro-tumorogenic Akt activation. Other examples of tumor suppressors include VHL, APC, CD95, ST5, YPEL3, ST7, and ST14.
example the promoter region), can cause a change in the protein structure, causing
o o
an increase of protein expression (through misregulation) an increase of protein (mRNA) stability, prolonging its existence and thus its activity in the cell
gene duplication (one type of chromosome abnormality), resulting in an increased amount of protein in the cell
There are 2 different types of chromosomal translocations that can occur: translocation events which relocate a proto-oncogene to a new chromosomal site that leads to higher expression
2.
1.
translocation events that lead to a fusion between a protooncogene and a 2nd gene (this creates a fusion protein with increased cancerous/oncogenic activity)
the expression of a constitutively active hybrid protein. This type of mutation in a dividing stem cell in the bone marrow leads to adult leukemia
Philadelphia Chromosome is an example of this type of translocation event. This chromosome was discovered in 1960 by Peter Nowell and David Hungerford, and it is a fusion of parts of DNA from chromosome 22 and chromosome 9. The broken end of chromosome 22 contains the "BCR" gene, which fuses with a fragment of chromosome 9 that contains the "ABL1" gene. When these two chromosome fragments fuse the genes also fuse creating a new gene: "BRC-ABL". This fused gene encodes for a protein that displays high protein tyrosine kinase activity (this activity is due to the "ABL1" half
of the protein). The unregulated expression of this protein activates other proteins that are involved in cell cycle and cell division which can cause a cell to grow and divide
uncontrollably (the cell becomes cancerous). As a result, the Philadelphia Chromosome is associated with Chronic
The expression of oncogenes can be regulated by microRNAs (miRNAs), small RNAs 21-25 nucleotides in length that control gene expression by downregulating them. Mutations in such microRNAs (known as oncomirs) can lead to activation of oncogenes. Antisense messenger RNAs could