Types of Mutation

Type of Mutation (Outline)
1. Gene Mutation
-Substitution - Eg of disease: Sickle Cell Aneamia
-Insertion (Frame Shift Mutation)
-Deletion (Frame Shift Mutation) - Eg of disease: Thalassemia
-Inversion

2. Chromosomal Mutation
A) Changes in Chromosomal Structure (Aberration)
-Inversion
-Deletion
-Translocation
-Duplication

B)Changes in Chromosomal Numbers
i)Aneuploidy
.Monosomy - Eg of disease: Turner Syndrome
.Trisomy - Eg of disease: Klinefelter's Syndrome & Down Syndrome
ii)Polyploidy
.Autopolypoidy
.Allopolyploidy- Eg: Halophyte Grass, Spartina Anglica(2n=122)

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1.Gene Mutation
-Gene Mutation is changes in nucleotide base sequence in a gene.
-The change of a single nucleotide base pair is called a point mutation.
-Gene mutation that causes alteration in reading frame of triplet code is known as frame shift mutation.
-Nonsense mutation mutates triplet code for an amino acids into a stop code (ACT,ATC, ATT)

~Substitution
-Only one nucleotide is replaced with different base
-Missense mutation produces different DNA sequence which will be transcribed into different mRNA compared with normal mRNA. mRNA will be translated producing polypeptide with different sequence.
-Nonsense mutation converts amino acids specifying codon on mRNA to termination(stop) codon.
Disease: Sickle Cell Anemia
-Haemoglobin is a quaternary structure protein that consist of 4 tertiary structure globular protein.
-2 of the globular proteins are made of alpha-polypeptides and another 2 is made of beta-polypeptide.
-beta haemoglobin polypeptide is a sequence of 146 amino acids linked by peptide bonds.
-The sixth amino acid is beta-polypeptide is Glutamate, it is represented by triplet code CTT in the gene for beta-polypeptide.
-To form sickle cell recessive allele (HBs), gene mutation involving single base pair substitution occurs.
-Nucleotide containing Thymine base in triplet code CTT is substituted with nucleotide containing Adenine to form new/mutated triplet code CAT.
-Triplet code CAT codes for Valine.
-In human that have 2 recessive allele for sickle cell, genotype (HBs HBs), sickle cell anaemia occurs.
-In these condition, globular proteins(tertiary) in haemoglobin made of beta-polypeptide becomes fibrous(secondary) if partial pressure of oxygen become low
-This causes red blood cell to become sickle.
-Sickle red blood cell is less efficient, it has reduced capacity to transport oxygen, anaemia occurs.
-Sickle cell anaemia patient need regular blood transfusion or bone marrow transplant.
-Heterozygous human, genotype (HBa HBs) have mild anaemia.

~Insertion (Frame Shift Mutation)
-Involves insertion or addition of base pairs.
-1 or 2 nucleotide base pairs are inserted into nucleotide sequence of a gene.
-Causes alteration of the reading frame - entirely new sequence of amino acid is produced after point of insertion.
-May cause nonsense mutation or produce new sequence of amino acid.

~Deletion (Frame Shift Mutation)
-Involves the loss of 1 or more nucleotide from a gene.
-Causes alteration of the reading frame - entirely new sequence of amino acid is produced after point of deletion.
-May cause nonsense mutation of produce new sequence of amino acid.
Disease: Thalassemia
-Thalassemia is a disorder that affects function of Red Blood Cell.
-There are 2 types of Thalassemia, alpha and beta Thalassemia.
-Each type is further divided into Thalassemia major and Thalassemia minor.
-Beta-Thalasssemia is more common.
-Beta-Thalassemia is caused by gene mutation involving single base pair deletion in the gene for beta-polypeptide.
-This causes synthesis of non-functional beta-polypeptide as frame shift mutation occurs.
-In human that are homozygous recessive for beta-Thalassemia have Thalassemia Major.
-Excess of alpha-polypeptide causes deformation of red blood cells, the red blood cells are destroyed by phagocyte(macrophage) in the body.
-Severe anaemia occurs because of lack of functional red blood cell.
-Destruction of Red Blood Cell and through intake of diet, the patient has excess iron ions.
-The patients has to go through iron chelation process to remove excess iron ions in body.
-Patient need regular blood transfusion or bone marrow transplant.
-Thalassemia minor patient have mild anaemia.

~Inversion
-Involves reversal of a portion of a nucleotide sequence.
-Base sequence after point of inversion remains same.


2. Chromosomal Mutation

A) Changes in Chromosomal Structure (Aberration)
-Chromosomal Aberration occurs due to structural changes in chromosome.

~Translocation
-is movement of a part of a chromosome to another part of genome or within same chromosome.
-Intra-chromosomal translocation is movement of a part of chromosome to another part of the same chromosome or homologous chromosome.
-Inter-chromosomal translocation is movement of a part of chromosome to another non homologous chromosome.

~Deletion
-Deletion is the loss of chromosomal fragment.
-Produces deletion loop between homologous chromosome.
-Eg: Cri-du-chat(cry like a cat) syndrome- small head, facial abnormalities and mentally retarded.

~Inversion
-Involves the change of direction of chromosomal segments.
-Results from a segment that has broken out of the chromosome and rejoins at the same site but with inverted direction.
-Produces inversion loop between homologous chromosome.

~Duplication
-Is the doubling of one or several chromosomal fragments.
-Involves the insertion of an extra copy of a region of the chromosome into a neighbouring position.


B)Changes in Chromosomal Numbers
-Chromosomal mutation involving changes in number of chromosome are caused by non-disjunction of chromosome.
-Non-disjunction of chromosome is failure of chromosome to segregate during cell division.
-Failure of segregation of homologous pairs occurs in Meiosis I while failure of segregation of sister chromatid occurs in Meiosis II or during mitosis.
-Eg of chromosomal mutation involving changes in number of chromosome is monosomy (2n-1) and trisomy (2n+1)
-Euploidy is the presence of normal number(2n) of structurally normal chromosome in genome/cell.

i)Aneuploidy
-Aneupoidy is the presence of abnormal number of chromosome that is caused by non-disjunction.

~Monosomy-Disease: Turner Syndrome (Sex chromosome Abnormalities)
-Female that have only one X chromosome, genotype 44+XO
-Female with this genotype may be produced through these situation.
.Non disjunction of sex chromosome occurs during oogenesis to produce ovum that lacks sex chromosome, genotype 22+O. This mutant ovum is fertilised with sperm containing X chromosome ,genotype 22+X.
.Non disjunction of sex chromosome during spermatogenesis to produce sperm that lacks sex chromosome, genotype 22+O. This mutant sperm is fertilised with normal ovum with genotype 22+X.
-Female with this syndrome have incomplete development of ovary, they are sterile and does not have menstrual cycle. They are usually mentally retarded.
~Trisomy- Disease: Klineflter's Syndrome (Sex chromosome Abnormalities)
-Male that have more than one X chromosome.
-The most common genotype is 44+XXY.
-Human that have genotype 44+XXY may be produce in these situation:
.Non disjunction of sex chromosome occurs during oogenesis in Meiosis I or Meiosis II to produce mutant ovum with genotype 22+XX. The ovum is fertilised by sperm that has Y Chromosome, genotype 22+Y.
.Non disjunction of sex chromosomes occurs during spermatogenesis in Meiosis II to produce mutant sperm with genotype 22+XY. The sperm fertilises normal ovum, genotype 22+X.
-Males with this syndrome are sterile because testis development is not completed.
-Because of the presence of 2 X chromosomes, they have development of female secondary sexual characteristic such as enlargement of breast.
-They are generally tall and have less body hair.

~Trisomy- Disease: Down Syndrome (Autosomal abnormalities)
-Down Syndrome occurs in human that have 3 chromosome number 21 in genome of a cell They have total 47 chromosome (normal:46) , they syndrome is also known as Trisomy-21.
-Non disjunction of chromosome no 21 occurs during gametogenesis to produce a gamete that have 2 chromosome no 21 besides normal number of other chromosome.
-The mutant gamete is fertilised by a normal gamate which has 1 chromosome no 21 and normal number of other chromosome.
-Human with Down Syndrome have low IQ, short-stocky body, slanted eyes, protruding tongue and simian cleft in head.



ii)Polyploidy
-Polyploidy is presence of multiple haploid number of chromosome in cell/genome. This organism may have 3n, 4n or higher haploid number.

~Autopolyploidy
-Autopolyploidy species originate from spontaneous or induced duplication of the genome of a single species. (eg: 2n>4n)

~Allopolyploidy
-Allopoluploidy species orginate from concurrent hybridization and duplication of the genomes of different species.
Eg: Halophyte Grass, Spartina Anglica(2n=122)
-Hybridization between S.maritima(2n=60) and S. alterniflora(2n=62) produces a hybrid plant, S. townsendii(2n=61)
-Meiosis cannot occur in S.townsendii because homologous chromosomes pairs are not present.
-Since reproductive cells(gamates) cannot be produced in S.townsendii, it is sterile and can only reproduce asexually through mitosis.
-Total non disjunction occurs during mitosis in the hybrid plant producing tetraploid, Spartina anglica (2n=122)
-Spartina Anglica can reproduce sexually because homologous pairs are present and meiosis can occur to produce haploid gamates
-Spartina Anglica is more fertile than its parental species