Download 4-genes-and-proteins-in-health-and-disease

Human Cells
Genes and proteins in health and
disease
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a. Protein structure and function
 What do you remember?
 Write down 10 words you associate with protein
structure and function
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What you need to know
 The elements that are found in proteins
 The bonds that build protein shape
 The variety and function of proteins
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Protein structure
 The elements making proteins are C, H, O, N and often S
 Amino acids are joined with peptide bonds (polypeptides)
 Hydrogen bonds form between amino acids giving initial
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folding or coiling (sheets/helices)
Sulfur bridges and other interactions between negative
and positive charges
More than 1 chain of amino acids can join together
Non protein molecules can be associated with proteins
3 dimensional shape
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Fibrous
Globular
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What type of protein?
 Collagen
 Somatotrophin
 Ligament
 Mucus
 Tubulin
• What type of protein are
these?
• What do they do?
• How is their structure
related to their function?
 Testosterone
 Trypsin
 Endorphins
 Immunoglobulin
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Types of protein
Protein structure allows protein function
 Enzymes – globular . Folded proteins exposing active sites
to binds specific substrate. Speed up biochemical
reactions.
 Structural proteins – fibrous often globular but too. Cell
membranes, muscle fibres
 Hormones – globular . Folded into specific shape to bind
to receptors at specific sites. Regulate growth and
metabolism
 Antibodies –globular Y shape . Bind to specific antigens
 Haemoglobin – conjugated. Protein with non protein
molecule attached to transport oxygen
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What do you know?
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Name the elements in proteins
State the number of amino acids in human proteins
Name the 3 types of bonds involved in protein structure
Name the 3 broad groups of protein
For each group of protein name an example
For each protein example describe how its structure relates to
its function
Complete the questions from page 50 in the textbook
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b. Mutations and their effect on
protein function
 What do you remember?
Write down 10 words you associate with mutations,
proteins and their function
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What you need to know
 Some types of gene mutations, what causes them and
how they affect protein function
 Some types of chromosome mutations, what causes them
and how they affect protein function or organism
function
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Mutations
 A change in an organisms genome
 Could be small with a single gene
 Could be larger change to chromosome structure or
number
 Occur spontaneously, naturally, randomly, rarely
 Rate can be artificially increased by mutagenic agents e.g.
UV light, X-rays, gamma rays, mustard gas etc.
 These mutations would be described as induced
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Mutations and protein function
 Proteins are essential for life
 Proteins are structural and control the metabolism
 If a gene coding for a protein mutates, the amino acid
sequence could be altered
 Faulty protein gives faulty structure or faulty metabolic
pathway
 If a gene coding for a protein mutates, the protein may
not be made at all
 Missing protein could mean non-functioning metabolic
pathway
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Gene mutations
 Mutations on a single gene would alter the nucleotide
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sequence
Point mutations are the change in one nucleotide
Could be deletion of one nucleotide changing all the
following codons and hence amino acid sequence.
Could be insertion of one nucleotide changing all the
following codons and hence amino acid sequence.
These two are both frameshift mutations
Could be the substitution of one nucleotide for another
altering only 1 codon and amino acid in the sequence
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Gene mutations - Normal
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Gene mutations - Deletion
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Gene mutations - Insertion
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Gene mutations - Substitution
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Gene mutations
 Splice site mutations
during processing of primary transcript mRNA the introns
are removed. Exons join together by splicing to give coding
for aa’s.
Splicing is controlled by nucleotide sequences at splice sites
on introns next to exons.
If a mutation occurs at splice sites some introns may be left
in and coded for in the mature mRNA
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Gene mutations
 Splice site mutations
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Gene mutations
 Nucleotide sequence repeat expansion
A mutation that produces a repeat of a triplet of
nucleotides (trinucleotide).
This inserted repeat of the same triplet codon (often many
times) stops the protein from functioning, due too many
aa’s.
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Gene mutations
 Nucleotide sequence repeat expansion
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How do gene mutations change
protein structure
 Substitutions alter only 1 codon so only 1 aa is affected
When the code still makes sense but is different from
original it is called a missense mutation.
When the code causes the sequence to stop being read as
the mutation produces a stop codon it is called a nonsense
mutation. The polypeptide chain is shortened and the
protein is not properly formed.
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How do gene mutations change
protein structure
 Splice site mutation (retaining introns)
Modifying mRNA can give altered protein structure.
 Frameshift (seen in nucleotide insertions or deletions)
These change all the codons after the change so all the
amino acids change after it.
The protein produced is likely to be non-functional
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How do gene mutations change
protein structure
 Nucleotide sequence repeat expansion
This is producing multiple copies of the same codon.
Can give extra amino acids of the same type.
Can expand the sequence so much that protein fails to be
produced.
Most of the gene mutations produce genetic disorders that
have adverse effects on the individuals who suffer from it.
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Effects on Health
Many gene mutations have an effect on the structure and
function of proteins.
These changes have an effect on health for e.g.
Sickle cell disease (anaemia)
PKU
Duchenne muscular dystrophy
Tay-Sachs syndrome
Cystic fibrosis
Beta thalessemia
Fragile X syndrome
Huntingdon’s disease
missense
missense
nonsense
frameshift insertion
frameshift deletion
splice site mutation
nucleotide sequence repeat expansion
nucleotide sequence repeat expansion
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Chromosome mutations
 These affect the structure of a whole chromosome.
 These include:
 Deletion where part of a chromosome is lost
 Duplication where part of the chromosome is repeated
 Translocation where 2 or more chromosomes rearrange
materials between them
Because these are such large changes they are often lethal
in their effect.
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Chromosome deletion
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Chromosome duplication
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Chromosome translocation
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What do you know now?
 What 2 effects can a mutation have on protein production?
 What are the 3 types of single gene mutation?
 What is a missense mutation?
 What is a nonsense mutation?
 What is a splice site mutation
 What 2 types of nucleotide changes are frameshift
mutations?
 What is a nucleotide sequence repeat mutation?
 What are the 3 chromosome mutations?
 What happens in each of these mutations?
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Consolidation
 Reading PPT, textbook or scholar and making own notes.
 Completing textbook questions page 50 and p62
 Answer multiple choice questions chapter 4
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