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Section C: Chromosomal Mutation

  1. Inversion :-A change in the linear sequence of one or more genes in a chromosome segment causes inversion mutation. In this type , the breaking and rejoining of a chromosome segment , in which a portion of chromosome separated and rotated 180 degree (flipped or inverted) before being rejoined at the breaking points into rest of DNA. No genes were lost or duplicated, but most likely non functional. Paracentric when the centromere is not part of inversion it is known as paracentric Pericentric when the centromere is part of inversion it is known as pericentric.

 

  1. Duplication:-A duplication consists of a piece of DNA in which additional copies of a gene are inserted into the genome.Duplication and deletions may occur at the same time in this process two homologous chromosomes break at the same moment at two different location and then exchange homologous portions.In this process one of the two chromosome have one or more genes missing(deletion) and the other have extra copy of the gene or genes(duplication). This type of mutation may alter the function of the resulting protein.

 

  1. Translocations:- In translocation mutation a section of DNA is removed from its original position and inserted in another location, either on same chromosome - intrachromosomal translocation or on a different chromosome -- interchromosomal translocation. Reciprocal translocation when chromosome segment from two non homologous chromosomes are exchanged as result two different translocation chromosomes are formed. Rarely this type mutation is found in nature.

 

  1. Induced mutation :-Mutation that are caused by chemical and physical agents due to which the DNA are damaged known as induced mutation. Chemical and physical agents that causes mutation are known as mutagens, substances that cause a much higher rate of mutation.Mutagen causes a heritable change in genetic material apart from the genetic recombination.

The mutation caused by mutagens are:-The chemical agents

  1. Deaminating agent :- Nitrous acid( HNO2) delaminates the bases G, C, and A. HNO2 ,delaminates adenine (A) to hypoxanthine(H) ,cytosine ( C)to uracil(U) and guanine (G)to xanthine (X) H pairs with C U pairs with A and X pairs with C. These mispairing can lead to transition mutations, base substitution.

 

  1. Base analogs :- These are compounds that chemically resemble nucleotide bases during DNA replication, they can be incorporated into the DNA in place of the natural base.

Examples:- 5-bromouracil(Bu), a compound that resembles thymine in shape and can pair with adenine just like thymine. It can base pair with adenine as well as with thymine, but it frequently tautomerizes to the enol form , which pairs with guanine causing transitions. 5-bromouracil(Bu), induce mutation.

  1. Alkylating agents :-Alkylating agents, such as ethyl methane sulphonate (EMS), ethyl ethane sulphonate (EES) and mustard gas, carry one (mono) , two (di) or more (poly )alkyl groups in are active form. DNA can be changed by alkylating agents.

The alkylated bases may inhibit DNA duplication or cause base pair mistake - 7-alkyl guanine may pair with thyamine instead of cytosine. The mispairing will lead to mutation.  Some alkylating agents may also cross-link DNA, resulting in chromosome breaks.

  1. Intercalating agents:-Some mutagens imitate the structure of a base pair rather than a single base for example proflavin and acridine orange. Acridine orange and other acridnes has three rings and resembles base pair in size and shape . It stack along base pairs in the DNA and this process is known as intercalation . During DNA replication, DNA polymerase misidentifies the intercalating agents for a base pair and puts in an extra base when making new strands Insertion of an extra base causes shift in the reading frame of the protein encoded by gene----frame -shift mutation---completely destroy the function of protein.