1. What are genetic disorders caused by?

2. Can you think of any examples?

Definition;

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.

Examples;

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

Genetic Disorders

• Name the 4 gene mutations that can occur• State the effect of gene mutations on amino

acid sequences

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 gasRadiation – gamma rays/ X-rays +

UV light

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

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

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

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

BUTProtects against malaria

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

Splice-site mutation

• Do you remember what splicing is?

Splicing ..... Hint .....

Exon

Protein

Translation

Processing

MaturemRNA

PrimarymRNA

Transcription

ExonIntron ExonIntronDNA

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.

• Splice-site mutations (creating or destroying the codons for exon-intron splicing).

• Diseases caused by splice-site

Substitution – replace a base;Splice-site

Beta (β) thalassemia

Exon 1

AlteredmRNA

DNADNA

AlteredmRNA

Exon 3Exon 3

IntronExon 2Intron Exon 1

Exon 1Exon 2

Exon 3 Exon 3Intron Exon 2 Intron

Exon 1

Creating codonDestroying codon

Single Gene (point) mutations -

• DIGS;

Deletion

Insertion

(Gene mutations)

Substitution

(inversion not in arrangements)

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 diseaseFragile X syndrome• Disease of insertion;Tay-Sachs syndrome

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

Frameshift; Deletion

• Nucleotide deletion of a nucleotide sequence is the removal of bases, causing a frame shift

• Examples of diseases;

Cystic Fibrosis

Consequences ??

• So if you tweaked the DNA – what is the consequence?

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.

Demonstrate your understanding

1. What are the types of gene mutations?

2. Which types do you think will have the greatest affect on the organism – explain/justify why.

3. Which mutations are frameshift mutations and can you explain why?

4. Which type of

mutations are

these;

Summary

Single Gene (Point) 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.

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 - www.ygyh.org

Success Criteria– Include the mutation type

– Inheritance information (hereditary/mutagenic agent)

– Symptoms/consequences

– Any treatments/therapies/preventions/screening

Mutations are always a negative thing

A gene mutation is a change in the genetic code

Gene mutations can result in cancer

Every characteristic of your body is coded for by one gene

Substitutions can be as harmful as additions

Cystic fibrosis is caused by the deletion of 3 bases

T

F

T

T

F

F

4 pictures 1 word – link?

Extension

• Talked about gene mutations

• Now think/write a definition of a chromosome mutation

Learning Outcomes

• Explain chromosome structure mutations

• Give some examples of chromosome mutations

• Compare gene to chromosome mutations

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.

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)

Examples ....

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

• The substantial changes in chromosome mutations often make them lethal!

• Now complete the worksheet

So what happens if chromosomes altered– what is the consequence?

Conclusion

• How frequent are mutations? (1)

• What is a mutant? (1)

• Name 4 mutagenic agents.(4)

• Name and describe 2 chromosome mutations.(4)

Your Presentations

• Come up and present