Lesson 5:Mutation(V)

Euploidy

• Euploidy/ polyploidy is the condition of an organism having 3 or more complete haploid sets of chromosomes 
• Polyploidy: 

                  * Occurs because of non-disjunction on all chromosome pairs, 
                     producing gametes with 3 or  more sets of chromosomes
                     (homologous)

                  *When fertilization takes place between a diploid gametes
                      and normal gamete new individual formed is triploid(3n)

                  * If fertilization occurs between 3 diploid opposite sex gametes, 
                     zygote formed is tetraploid(4n) 

It can be classified into 2:            

Autopolyploidy

• Autopolyploidy is polyploidy in which there are three or more sets of chromosomes within the same species
• Domestic banana and various seedless plants are often triploid autoployploids.

            Examples:

                 *Colchine is a chemical use to disrupts arrangement of microtubule 
                   to form spindle fibres during cell division(cytokinesis). It is used to
                   induce formation of economically important polyploidy plants to 
                   produce bigger leaves, large flowers, fruits and seeds.

Lesson 4:Mutation (IV)

Chromosomal Mutation

There are 2 types of chromosome mutation:

1. Change in chromosome number
2. Change in chromosome structure  

(a) Change in chromosome number

These are usually caused by non-disjunction occurring during meiosis but they can also occur during mitosis.

There are 2 types: 

Aneuploidy

• It is a condition of a nucleus, cell or organism in which one or more chromosomes have been added to or deleted from the complete set such that total no. of chromosome in not exact multiple of the haploid number 
• Aneuploids are diploid cells or organisms that have lost or gained 1 or more chromosomes. 
• Monosomy is the condition of diploid cells or organisms lacking in a single chromosome  
• Example: Turner syndrome( 45, XO) 
• Trisomy is the condition of diploid cells or organisms with an additional chromosome( 2n+1). 
• Example: Trisomy 21 (down syndrome) and Klinefelter syndrome (47, XXY) 
• Disjunction is the separation of homologous chromosomes or sister chromatids in anaphase to opposite poles of a dividing cell. 
• Non- disjunction is the failure of a pair or pairs of homologous chromosomes to separate and move to opposite poles of the cell  
• Happen during: 

                      Anaphase I meiosis  --homologous chromosome fail to separate normally

                      Anaphase II meiosis   -- sister chromatids fail to separate  normally

• Mitosis –where sister chromatids fail to separate 
• As a result of non-disjunction, one gamete receives two copies of the gene while the other gamete receives none. In the next step, the faulty gametes engage in fertilization, the offspring will have an incorrect chromosome number. This is called aneuploidy.
 

Down syndrome

• Down syndrome or trisomy 21 is a chromosomal disorder caused by the presence of an extra 21st chromosome.
• Individuals with Down’s syndrome have three instead of the normal 2 chromosomes 21.
• This occurs when a mutant gamete that has 2 chromosomes 21 fertilises a normal gamete with one chromosome 21.
• Mutant gamete with 2 chromosome 21 can be produced by:

                  *  Non-disjunction of homologous chromosome pair 21 
                      occurs during anaphase I of meiosis

                  * Non-disjunction of sister chromatids of chromosome 21
                     occurs during anaphase II of meiosis 

• Individuals with Down syndrome tend to have a lower than average cognitive ability, often ranging from mild to moderate learning disabilities. 

Klinefelter's syndrome

• Occurs when a male inherits more than one X chromosome producing genotypes such as 47+ XXY( XXY, XXYY, XXXY)
• Caused by non-disjunction of sex chromosome during meiosis
• Affected males have an extra X sex chromosome. The principal effects are development of small testicles and reduced fertility. 
• Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males".   
• Affected males are almost always effectively sterile, although advanced reproductive assistance is sometimes possible. 
• Some degree of language learning impairment may be present, and neuropsychological testing often exhibit deficits in executive functions. 
• In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky (thin & tall person), youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). 
• Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population, but only about 10% of XXY males' gynecomastia is noticeable enough to require surgery.

Turner syndrome

• An example of monosomy in the human population. Female individuals have only 45 chromosomes (45,X).It is caused by the absence of a second X chromosomes. Non-disjunction of sex chromosomes occur during anaphase.
• In females, non-disjunction produces gametes with XX chromosomes or no sex chromosomes. In males, this produces gametes with XY chromosomes or no sex chromosomes. When a gamete a normal X chromosomes fuses with a gamete without X chromosomes, the zygote formed contains monosomy X (XO).

 

Lesson 3: Mutation(III)

(c) Base Deletion

It is the removal of a base from a normal gene sequence. Like insertions, these mutations can alter the reading frame of the gene. When a nucleotide base pair is deleted from DNA base sequence of a gene, this causes the whole base sequence (reading frame) to be shifted one place forward. In this frameshift mutation, every single triplet code after the deletion point is altered. 

During transcription, the codons assembled in mRNA after mutation point are also different. This gives rise to the production of a different polypeptide with a primary structure containing an incorrect sequence of amino acid. Deletion or insertion more harmful than substitutions or inversion because it leads to production of non-functional protein or enzyme.

Beta (ß)- Thalassaemia Major (Cooley’s anaemia)

 
What is thalassaemia?

It is a group of inherited genetic disorders that cause defective haemoglobin production. Many types of thalassaemia include alpha and beta thallasaemia. There are 2 types of ß-thalasaemia which are ß-Thalassaemia Major( Cooley’s anaemia)and ß-Thalassaemia Minor.

Causes

It is caused by Lack of ß-polypeptide chains and relative excess of α-polypeptide chains. Α-polypeptide chains form insoluble aggregates that precipitate within erythrocytes. This causes damage to cell membranes and render the destruction of erythrocytes by phagocytes. Erythroblasts in the bone marrow also destroyed with an increased absorption of excessive dietary iron

Sign and symptoms

Most children with Cooley’s anaemia appear healthy at birth but within 1^st 2 year of life they become pale, listless and fussy with poor appetite. They grow slowly and often develop jaundice. Red blood cell also smaller in size. Without treatment, the spleen, liver and heart become enlarged and bones become thin and brittle.

Treatment

The patient needs a frequent blood transfusions and the use of antibiotics. Bone marrow transplant or stem cell gene therapy is also encourageable.

Different Between Frameshift and Non-Frameshift Mutation


Frameshift Mutation

• Causes alteration of the whole sequence (reading frame) of nucleotides bases. Every single triplet genetic codes after mutation point is altered  
• Result in a different DNA strands synthesized during semiconservative replication. An altered mRNA with many different codons is produced during transcription. this leads to formation of an incorrect series of amino acids in polypeptide chain.
• It usually have more severe effects on the phenotypes and sometimes lethal to the organisms.
• Insertion and deletion of nucletides bases is the example but they won't cause a change in the reading frame after mutation point.

Non-frameshift Mutation

• It doeas not cause the alteration of the whole nucleotide base sequence
• only the mutated single code in the DNA and single codon in mRNA are affected. Therefore, only one amino acid is different in the resultant polypeptide that is synthesized.
• If different amino acid is located within the active site of an enzyme or involved in the folding of a particular protein, this would affect functioning of the enzyme or protein
• Examples: Substitution and inversion

           

Lesson 2: Mutation (II)

2. Gene Mutation/Point mutation

Gene mutation is a change in sequence of nucleotide bases of the DNA. It occurs at a single locus on a chromosome. There are 4 types of gene mutation:

(a) Base Insertion (addition) 

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element. Effects of insertion/deletion of 3 nucleotide bases are less serious than insertion of 1/2 nucleotide bases. This is due to no shifting of DNA base sequence after the insertion point.  Only 1 amino acid residue is added or deleted in the new polypeptide chain.

Sorry...I cant find any pic on the internet so I'll use my method to describe what is base insertion:

    CTGGAG

CTGGTGGAG

• As what you can see, there is a base(TGG) adding to the base sequence which alter the DNA sequence but it is less serious.

(b) Base Substitution

A substitution is a mutation that one base is replaced by another base (i.e., a change in a single "chemical letter" such as switching an A to a G). If a purine (A , G) replaces a purine or pyrimidine (C,T) replaces pyrimidine, it is called Transition Substituition. If a purine replaces a pyrimidine or vice versa, this is a Transverse Substituition. Substituition mutations are usually missence mutations. The new nucleotide base alters one genetic code to a different code.

CTGGAG
CTGGGG

The change of a single nucleotide--can also change a codon so that a different protein is specified, a non-synonymous change. This is called a missense mutation, since the wrong amino acid is specified. The protein coded by the gene therefore has a change to a single amino acid. This often has no significant effect on the protein, as most can tolerate a few amino acid changes without their biological function changing. On the other hand, sometimes a missense mutation does have a significant effect. Many Fanconi Anemia mutations are missense mutations.

For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced.

ATG   GAA   GCA   CGT                       Change to                 ATG   GAC   GCA   CGT 

MET   GLU   Ala      Gly                          Change to                 MET   Asp     Ala      Gly

In nonsense mutation, new base changes a codon that encodes a particular amino acid into one of the stop codon. Translation of mRNA is terminated and a shorter or nonfunctional protein is produced.

ATG   GAA   GCA   CGT                    Change to                 ATG   TAA   GCA   CGT 

MET   GLU   Ala      Gly                       Change to                 MET   STOP

Silent mutation does not alter polypeptide formed because mutated codon still encodes for the same amino acid. It can only detected by sequencing the nucleotide bases of the gene.

Sickle-cell anaemia

Substitution of a base thymine by adenine in the gene that codes for the beta polypeptide chain. This changes triplet code ( CTT( for glutamic acid) CAT (valine). This causes alteration of the ß-polypeptide chain. In active body tissues where oxygen concentration is low, altered ß-chains tend to stick together forming long fibres and abnormal haemoglobin molecules crystalline. The red blood cells are pulled into sickle shape. These cells have a lower affinity to bind oxygen and are easily trapped within capillaries causing a reduction in oxygen supply to tissues and damage to organs such as the kidney.

Lesson 1: Mutation

1. Classification of mutation

Mutations are changes to the nucleotide sequence of the genetic material of an organism.  Mutation may cause changes in the number, structure of chromosomes or structure of gene. It may also cause changes in phenotype or physiological processes in the organism. There are 2 types of mutation:

Spontaneous mutation 

Mutation which appear suddenly. They may originate as errors during DNA replication or from chemical        changes in the DNA’s nitrogenous base.

Induced mutation 

Mutation which caused by mutagen such as radioactive material or methylating agents. these agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions. 

Effect of Mutation

• Synthesis of a non-functional/faulty protein

• Lowers production of a particular protein

• Prevents the synthesis of a protein

• Adds more nucleotides bases to the gene, giving the protein product  new function which may be harmful to the cells

In multicellular organisms, mutations can be subdivided into :-

Germ line mutations, 

It is a mutation which can be passed on to descendants

Somatic Mutation

A mutation which are not transmitted to descendants in animals. The individual has different genotypes in the somatic cells but have developed from the same zygote. The individual is known as genetic mosaic. Somatic mutation only occur in somatic cells or tissues and are not transmitted. These mutation can only reproduce by mitosis. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant). 

Types Of Mutagens 

. 1. Ionising radiation(e.g: X-rays, alpha&beta particles, cosmic rays)   

• It can cause molecules to lose electron and production of highly reactive free radicals. It can cause aberrations/ difference in chromosomes and genes including breaks in DNA strands, destructive of  nucleotide bases.

.2. Non-ionising radiation (e.g: UV rays)

•  It causes molecular vibration or ejection of electron to higher energy level and cause breaking and formation of new chemical bonds which causes alteration of DNA strands. For Example: U.V light causes breakage of A & T bases and cause cross covalent bonds occurs between 2 adjacent thymine to form thymine dimer which cause distortion of DNA helix, prevent normal base pairing and impede replication or transcription