Gene Mutations

Gene Mutations

O A mutation is a permanent change in the DNA sequence of a gene.

O Any change in this sequence is likely to change the message transcribed into mRNA which will in turn alter the amino acid sequence causing a change in the structure and function of the protein being coded for.

Gene Mutations

OIf a nucleotide is added, deleted or changed the sequence of codons in the transcribed mRNA is changed and therefore the resulting chain of amino acids is altered.

1. POINT MUTATIONSO Are single nucleotide base changes in

a gene’s DNA sequence. This type of mutation can change the gene’s protein product in the following ways:

O Normal Line of Un-Mutated DNA:Normal DNA TAC TGC ACC GGT ACTmRNA AUG ACG UGG CCA UGAprotein met thr try pro stop

Missense mutationsO Missense mutations are point mutations

that result in a single amino acid change within the protein.

Mutated DNA TAC TGC AAC GGT ACTmRNA AUG ACG UUG CCA UGAprotein met thr leu pro stopO LEU CHANGED FROM TRY

O For example, in sickle-cell disease, the 20th nucleotide of the gene for the beta chain of hemoglobin found on chromosome 11 is changed from the codon GAG (for glutamic acid) to GUG (which codes valine), so the 6th amino acid is incorrectly substituted.

Nonsense mutationsO Nonsense mutations are point

mutations that create a premature “translation stop signal” (or “stop” codon), causing the protein to be shortened.

Mutated DNA TAC TGC ATC GGT ACT

mRNA AUG ACG UAG CCA UGAprotein met thr STOPO STOP CHANGED FROM TRY

O Nonsense Mutations for cystic fibrosis have been found in almost 1000 combinations. Each of these mutations occurs in a huge gene that encodes a protein (of 1480 amino acids) called the cystic fibrosis transmembrane conductance regulator (CFTR). Unlike a missence mutation in sickle cell anemia, it can be various mutations that cause cystic fibrosis.

O Ex: The substitution of a T for a C at nucleotide 1609 converted a glutamine codon (CAG) to a STOP codon (TAG). The protein produced by this patient had only the first 493 amino acids of the normal chain of 1480 and could not function.

Silent mutations

O Silent mutations are point mutations that do not cause amino acid changes within the protein.

Mutated DNA TAC TGA ACC GGT ACT

mRNA AUG ACU UGG CCA UGA

protein met thr try pro stop

O THR still codes for THR O There is no example of a silent mutation because

it does not affect the organisms phenotype.

2. FRAMESHIFT MUTATIONS

O Result in a shift of the “reading frame” during protein translation.

O There are two different types

Insertion MutationsO Insertion mutations add one or more

DNA bases which changes the grouping of nucleotide bases into codons.

O Frameshifts often create new STOP codons and thus generate nonsense mutations. Just as well as the protein would probably be too garbled to be useful to the cell.

Mutated DNA TAC TAG CAC CGG TAC TmRNA AUG AUC GUG GCC AUG Aprotein met iso val ala met O A base inserted at the 5th spot, shifting all the

bases down.

Deletion MutationsO Deletion mutations remove one or

more DNA bases which changes the grouping of nucleotide bases into codons.

Mutated DNA TAC TGC CCG GTA CTmRNA AUG ACG GGC CAU GAprotein met thr gly hisO 13th base is removed, eliminating 1

amino acid.

OCri du chat syndrome, also known as chromosome 5p deletion syndrome, is a rare genetic disorder due to a missing part of chromosome 5. Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children due to problems with the larynx and nervous system. About 1/3 of children lose the cry by age 2.

O Other symptoms of cri du chat syndrome may include:

O feeding problems because of difficulty swallowing and sucking.

O low birth weight and poor growth.O severe cognitive, speech, and motor delays.O behavioral problems such as hyperactivity,

aggression, tantrums, and repetitive movements.

O unusual facial features which may change over time.O excessive drooling.

Introns and Exons 

OExons – segments of DNA that code for amino acids that will become part of a protein.

OExons are not found next to each other. They are separated by sections of DNA called introns.

 

O Introns – segments of DNA that do not code for amino acids of a protein.

O When a gene is transcribed, both the introns and exons are made into RNA.

O The introns must then be cut out and the remaining exon pieces must be joined together.

O Before this happens, two other strings of nucleotides are added to the ends of the RNA. One is called a cap and the other is called a tail.