CONCEPT OF MUTATION AND ITS CLASSIFICATION .pptx

The presentation focuses on the concept of mutation and its different types of classifications.
It describes the different types of mutagens, classification of mutations based on its transmission, based on its effect on encoded protein and based on its effect on the functions of proteins.

1. TYPES OF MUTATION Dr. A. T. Sharma Assist. Professor Nanded Pharmacy College, Nanded

2. Introduction The permanent change in sequence of nucleotides. May occur in somatic cells or germ line cells Mutation in somatic cells does not pass to future generations while mutation in germ line cells may be passed to future generations Mutation may be in coding sequences (hereditary disorder or disease) or in non-coding sequences Mutation may occur due exposure to mutagenic agents and errors through DNA replication and repair

3. Mutagens Anything that causes a mutation (a change in the DNA of a cell) . DNA changes caused by mutagens may harm cells and cause certain diseases, such as cancer. Examples of mutagens include radioactive substances, x-rays, ultraviolet radiation, and certain chemicals. Types of Mutation Based on transmission: Depending upon transmission from one generation to generation, mutation can be classified in to – Stable/fixed mutations: Mutation transferred unaltered (unchanged) Unstable/dynamic mutations: Mutation undergo variations as they pass on to families

4. Stable/fixed mutations: Classified on the basis of the particular molecular alterations at the DNA level as – Substitution: Replacement of a single nucleotide by another. - Two kinds of substitutions – - Transition: Replacement by the identical nucleotide. E.g. a pyrimidine for a pyrimidine (C for T or vice versa) or a purine for a purine ( A for G or vice versa) - Transversion: Replacement by the different nucleotide Insertion: Addition of one or two or more nucleotides in to a gene. - If insertion in coding sequence and includes one, two or nucleotides which are not multiple of three, it will interrupt the reading structure.

5. Deletion: Complete loss of one or more nucleotides - If insertion in coding sequence and includes one, two or nucleotides which are not multiple of three, it will interrupt the reading structure. Duplication: Doubling of one or more nucleotides.

6. Unstable / dynamic mutations: Contain triplet replication sequences which, in affected persons, arise in enlarged copy number as compared to the overall population. Repeats of three nucleotides increase in copy numbers until they cross the threshold above which they become unstable. Defective proteins, change in regulation of gene expression, synthesis of toxic RNA, chromosomal instability. Triplet increase or expansion has been recognized the mutational origin for number of different single gene disorders known as trinucleotide repeat disorders. Larger the expansion, faster the onset and more is the severity of disease. Mechanism is unknown.

7. Based on the effect on the encoded protein: Depending upon the basis of effect on the polypeptide sequence of the encoded protein, two classes as - Synonymous or silent mutation: A mutation does not change the polypeptide product of the gene A single base-pair substitution, particularly at third position of a codon, produces a codon coding for the same amino acid – no change in properties of the protein. Non-synonymous mutations: A mutation leading to change in the encoded polypeptide Abnormal protein function

8. Occurs in one of the three main ways: - Missense: A single base-pair substitution resulting in coding for different amino acid and production of a changed protein. - May or may not disturb protein function Conservative substitution: Mutation coding for a chemically similar amino acid and hence no effect on protein function Non-conservative substitution: Mutation coding for a chemically dissimilar amino acid and hence effect on protein structure – complete loss or reduction of biological activity

9. - Nonsense: A substitution of base-pair leading to the generation of one of the stop codons – results in premature termination of translation of a peptide chain – reduces the biological activity of the protein. - Frameshift: Insertion or deletion of nucleotides not in a multiple of three disturbing the interpretation of frame - Usually insert premature STOP codons (along with large number of amino acid changes, effect on protein structure) - Reading of codon is changed, STOP codon may not be read or may be added later or earlier site - Protein produced may be unusually short, abnormally long and/or contain wrong amino acids – nonfunctional protein - Severe genetic diseases like Tay-Sachs disease, familial hypercholesterolemia

10. Frameshift mutation

11. Based on functional effects of mutations on the protein: The mutations effect can appear as any of the following: Loss-of-function mutations ( I nactivating mutations): Mutations that result in the gene product having less or no function (being partially or wholly inactivated). When the allele has a complete loss of function ( null allele ), it is often called an  amorph  or amorphic mutation. Loss of function mutations are generally recessive. E.g. a nonsense mutation that causes polypeptide chain termination during translation. 

12. Gain-of-function (Activating mutations):   M utations that change the gene product such that its effect gets stronger (enhanced activation) or even is superseded by a different and abnormal function. When the new allele is created, a  heterozygote  containing the newly created allele as well as the original, will express the new allele ( dominant  phenotypes). Hypermorph (increased gene expression) and neomorph (novel function).  E.g. Loss of growth control as in oncogenes

13. Thank You…!!! (Disclaimer: The images and diagrams in this presentation have been downloaded from the google source. I am grateful to all the publishers & the google.)