1. 1. What are genetic disorders caused by. 2
1. What are genetic disorders caused by? 2. Can you think of any examples?
BELLWORK

2. Genetic Disorders Definition; Examples;
Genetic disorders are caused by changes to genes or chromosomes that result in the proteins not being expressed or the proteins expressed not functioning correctly.
Sickle cell anaemia Duchenne muscular dystrophy Tay-Sachs syndrome Cystic fibrosis Huntingdons Fragile X syndrome Beta thalassemia PKU Cri-du-chat syndrome Chronic myeloid leukaemia Down’s syndrome

3. Learning Outcome Name the 4 gene mutations that can occur
State the effect of gene mutations on amino acid sequences

4. Mutation Types
Mutation – change in structure/composition of organisms genome
If the change in the genotype is in phenotype – individual is called mutant
Mutations are random occurrences (spontaneously) and low frequency (rarely) ROLF!
Mutagens/ mutagenic agents can artificially increase the rate of mutations.
Thus these mutations are called
induced
Chemicals include – mustard gas
Radiation – gamma rays/ X-rays +
UV light

5. Mutation Types
Single gene mutations involve the alteration of a DNA nucleotide sequence;
Point Mutations
Substitution (missense, non-sense and splice-site)
(Inversion)
Frameshift Mutations
Insertion
Deletion
Gene Mutations Video

6. Gene Mutations
SINGLE GENE MUTATIONS – involve changes in one nucleotide
(deletion, insertion and substitution)
bring about only a minor changes as only 1 nucleotide (ie one different amino acid); sometimes the organism is affected only slightly or not at all
FRAMESHIFT MUTATIONS – (insertion & deletion) leads to a large portion of the gene’s DNA to be misread; the protein produced differs from the normal protein by many amino acids and is usually dysfunctional

7. Substitution – replace a base; Missense
Single-nucleotide substitutions include: missense (replacing one amino acid codon with another).
Diseases caused by missense;
Sickle-cell disease
PKU

8. Sickle cell anaemia
Blood disorder where rbc change shape into an abnormal, rigid , sickle shape.
This causes problems such as blocking blood vessels
Delayed growth
Fatigue
Shorter life
Infections
Jaundice
BUT
Protects against malaria

9. Substitution – replace a base; Non-sense
Single-nucleotide substitutions include: non-sense (replacing one amino acid codon with a premature stop codon).
Diseases caused by nonsense;
Duchenne muscular dystrophy DMD

10. Splice-site mutation
Do you remember what splicing is?

11. Splicing ..... Hint ..... DNA Exon Intron Exon Intron Exon
Transcription
Primary
mRNA
Processing
Mature
mRNA
Translation
Protein

12. Splice-site mutation Do you remember what splicing is?
Splicing is the post transcription and pre- translational of mRNA ; removing introns and exons joined together (primary to mature mRNA), then using certain exons (alternative splicing)
Splicing is controlled by a specific nucleotide sequence at the splice site on introns which flank (beside) exons. Mutation occurs here.

13. Substitution – replace a base; Splice-site
Splice-site mutations (creating or destroying the codons for exon-intron splicing).
Diseases caused by splice-site
Beta (β) thalassemia
Splice-site mutations occur within genes in the noncoding regions (introns) just next to the coding regions (exons). They can have profound effects on the resulting protein, which may lead to disease. Before mRNA leaves the nucleus, the introns are removed and the exons are joined together. This process is called splicing. Splicing is controlled by specific intron sequences, called splice-donor and splice-acceptor sequences, which flank the exons. Mutations in these sequences may lead to retention of large segments of intronic DNA by the mRNA, or to entire exons being spliced out of the mRNA. These changes could result in production of a nonfunctional protein.
Destroying codon
Creating codon
DNA
Exon 1
Intron
Exon 2
Intron
Exon 3
DNA
Exon 1
Intron
Exon 2
Intron
Exon 3
Altered
mRNA
Exon 1
Exon 2
Exon 3
Altered
mRNA
Exon 1
Exon 3

14. Single Gene (point) mutations -
DIGS;
Deletion
Insertion
(Gene mutations)
Substitution
(inversion not in arrangements)

15. Frameshift; Insertion & repeat expansion
Nucleotide insertions or an expansion of a nucleotide sequence repeat (essentially insertion of a large number of copies of the nucleotide sequence).
Results in extra copies of amino acid/ or fails to express (silenced)
Examples of repeat expansion diseases;
Huntingdon's disease
Fragile X syndrome
• Disease of insertion;
Tay-Sachs syndrome

16. Tay-Sachs syndome
Recessive chromosome 15 disease that affects the nervous system.
Body lacks hexosaminidase A (protein which breaks down chemicals in ganglioside, fatty substance GM2, thus builds up and prevents nerve functioning)
Slow development at 6 month
Loss of movement/ vision/hearing
Most die at 5yrs old

17. Frameshift; Deletion
Nucleotide deletion of a nucleotide sequence is the removal of bases, causing a frame shift
Examples of diseases;
Cystic Fibrosis

18. Consequences ??
So if you tweaked the DNA – what is the consequence?

19. So if you tweaked the DNA – what is the consequence?
The effect of missense, nonsense, splice-site, frameshift and nucleotide sequence repeat expansion mutations
On the structure of the protein synthesised, its function and the effect of this on individuals.

20. Demonstrate your understanding
What are the types of gene mutations?
Which types do you think will have the greatest affect on the organism – explain/justify why.
Which mutations are frameshift mutations and can you explain why?
Which type of
mutations are
these;
Insertion – 1, deletion – 2, substitution – 3

21. Summary Single Gene (Point) mutations Frameshift mutations
Point mutations occur at a single point – substitution.
They are generally not harmful, most of the protein remaining unaffected.
Since only one amino acid is affected, the protein will probably be functional.
(single nucleotide polymorphism)
Frameshift mutations
After a deletion or insertion the open reading frame is moved one base pair forwards or backwards.
This is generally harmful since all the amino acids in the primary structure of the protein will have changed from the mutation onwards.
The protein will probably be non-functioning.

22. Homework For next week in pairs;
Prepare a presentation on a genetic disorder (PKU/Beta (β) thalassemia/DMD/CF/Fragile X/Huntingdon’s/Cri-du-chat syndrome or chronic myeloid leukemia)
Try website/books/library -
Success Criteria
Include the mutation type
Inheritance information (hereditary/mutagenic agent)
Symptoms/consequences
Any treatments/therapies/preventions/screening

23. true or false F T T F F T Mutations are always a negative thing
A gene mutation is a change in the genetic code T
Gene mutations can result in cancer F
Every characteristic of your body is coded for by one gene F
Substitutions can be as harmful as additions T
Cystic fibrosis is caused by the deletion of 3 bases

24. 4 pictures 1 word – link? Extension Talked about gene mutations
Now think/write a definition of a chromosome mutation

25. Learning Outcomes Explain chromosome structure mutations
Give some examples of chromosome mutations
Compare gene to chromosome mutations

26. Structure of a chromosome altered!
These mutations can take the form of a;
Deletion (loss of a segment of a chromosome)
Duplication (repeat of a segment of a chromosome)
Translocation (the rearrangement of chromosomal material involving two or more chromosomes).
The substantial changes in chromosome mutations often make them lethal.

27. Examples ....
Cri-du-chat syndrome (deletion of part of the short arm of chromosome 5)
Chronic myeloid leukemia (CML) (reciprocal translocation of a gene from chromosome 22 fused with a gene on chromosome 9)

28. Examples ....
Familial Down’s syndrome (in 5% of cases one parent has the majority of chromosome 21 translocated to chromosome 14)

29. So what happens if chromosomes altered– what is the consequence?
The substantial changes in chromosome mutations often make them lethal!
Now complete the worksheet

30. Conclusion How frequent are mutations? (1) What is a mutant? (1)
Name 4 mutagenic agents.(4)
Name and describe 2 chromosome mutations.(4)

31. Your Presentations
Come up and present