1. Gene Mutations

2. 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.

3. Gene Mutations O If 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.

4. 1. POINT MUTATIONS O 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 DNATAC TGC ACC GGT ACT mRNAAUG ACG UGG CCA UGA proteinmetthr try pro stop

5. Missense mutations O Missense mutations are point mutations that result in a single amino acid change within the protein. Mutated DNATAC TGC AAC GGT ACT mRNAAUG ACG UUG CCA UGA proteinmet thr leu pro stop O LEU CHANGED FROM TRY

6. 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.

7. Nonsense mutations O Nonsense mutations are point mutations that create a premature “translation stop signal” (or “stop” codon), causing the protein to be shortened. Mutated DNATAC TGC ATC GGT ACT mRNAAUG ACG UAG CCA UGA proteinmet thr STOP O STOP CHANGED FROM TRY

8. 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.

9. Silent mutations O Silent mutations are point mutations that do not cause amino acid changes within the protein. Mutated DNATAC TGA ACC GGT ACT mRNAAUG ACU UGG CCA UGA proteinmetthr 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.

10. 2. FRAMESHIFT MUTATIONS O Result in a shift of the “reading frame” during protein translation. O There are two different types

11. Insertion Mutations O 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 DNATAC TAG CAC CGG TAC T mRNAAUG AUC GUG GCC AUG A proteinmet iso val ala met O A base inserted at the 5th spot, shifting all the bases down.

13. Deletion Mutations O Deletion mutations remove one or more DNA bases which changes the grouping of nucleotide bases into codons. Mutated DNATAC TGC CCG GTA CT mRNAAUG ACG GGC CAU GA proteinmet thr gly his O 13 th base is removed, eliminating 1 amino acid.

14. O Cri 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.

15. 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.

16. Introns and Exons O Exons – segments of DNA that code for amino acids that will become part of a protein. O Exons are not found next to each other. They are separated by sections of DNA called introns.

17. 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.