Genes and proteins in Health
and Disease
What you should know
• Proteins are held in a three dimensional
shape by peptide bonds, hydrogen bonds,
interactions between individual amino
acids.
• Polypeptide chains fold to form the three
dimensional shape of the protein.
PROTEIN - STRUCTURE
AND FUNCTION
PROTEIN STRUCTURE
• Proteins are made from long chains of
amino acid molecules.
• The amino acids are linked by peptide
bonds.
• A chain of amino acids is called a
polypeptide chain
PROTEIN PRIMARY
STRUCTURE
• The primary
structure of a
protein is the
polypeptide chain
of amino acids
PROTEIN SECONDARY
STRUCTURE
• Weak hydrogen
bonds form between
various amino acids.
• This causes the
polypeptide chain to
become coiled into
an  helix (coiled) or
folded into a 
pleated sheet
(folded)
PROTEIN TERTIARY
STRUCTURE
• The tertiary structure
is the final structure of
the protein due to
hydrogen bonding and
sulphide bonding
between amino acids.
• tertiary structure can
form either fibrous
proteins or globular
proteins.
PROTEIN QUARTERNARY
STRUCTURE
• Quarternary
structure is formed
when several
polypeptides become
bonded together
FIBROUS PROTEIN
• Formed when several
polypeptide chains are
bonded together in long
parallel strands
• examples include collagen
(skin), keratin (hair) and
actin and myosin (muscle)
GLOBULAR PROTEINS
• Look like a tangled
ball of string
• Enzymes, hormones
and antibodies are
all globular proteins
CONJUGATED PROTEIN
• Contains polypeptide
chains and a nonprotein part
• E.g. haemoglobin
consists of 4
polypeptide chains
and 4 iron atoms
Functions of proteins
• Enzymes e.g. amylase
• Structural proteins e.g. a component of
the cell membrane
• Hormone e.g. insulin
• antibodies
Mutations- What you should know
• Mutations result in no protein or a faulty protein being expressed.
• Single gene mutations involve the alteration of a DNA nucleotide
sequence as a result of the substitution, insertion or deletion of
nucleotides.
• Single-nucleotide substitutions include: missense, nonsense and
splice-site mutations.
• Nucleotide insertions or deletions result in frame-shift mutations or
an expansion of a nucleotide sequence repeat.
• The effect of these mutations on the structure and function of the
protein synthesised and the resulting effects on health.
• Chromosome structure mutations – deletion; duplication;
translocation.
• The substantial changes in chromosome mutations often make them
lethal.
What is a mutation?
• It’s a change in the structure or composition
of an organisms’ DNA
• This can lead to no protein or a faulty protein
being expressed
MUTATIONS
•
•
•
•
Occur naturally in every population
They can occur spontaneously
They cause a change in the organism’s DNA
An individual with a mutation is termed a
mutant
• The frequency of mutations can be increased
by mutagenic agents e.g. chemicals & radiation
EXAMPLES
• Polydactyly –
presence of extra
finger or toes
• Liam Gallagher and
Marilyn Monroe!!
Single Gene Mutations
• Changes in one or more nucleotides in
the DNA of the cell
- Substitution
- Insertion
- Deletion
Substitution Mutations
• One nucleotide is
replaced with
another
• Missense- mutation ends up coding for wrong amino acid
• Nonsense- mutation causes codon to be replaced by
STOP codon , so no amino acid produced
• Splice-site mutations- intron/exon splice is affected and
an intron may be retained in error
Sickle Cell Anaemia
PKU
• Phenylketonuria
tyrosine
phenylalanine
enzyme
MUTATION
gene
Insertion Mutations
• The addition of one
or more nucleotides
into the DNA
• Codons in mRNA
that appear after
the mutation have
changed
• as a result, the
amino acids in the
All amino acids altered
protein are also different
• A type of mutation which has this effect is called a
frameshift mutation.
Deletion Mutations
• The removal of one or more nucleotides from the DNA
• Making it another example of a frameshift mutation
All amino acids altered
Cystic Fibrosis
Point Mutations
• Any mutation involving a single nucleotide
• Could be substitution, insertion or deletion
• Minor changes to individual amino acids
Frameshift Mutations
• Insertion and deletion mutations
• The loss or gain of 1 or 2 nucleotides causes the affected
codon and all of the codons that follow to be misread.
This leads to a very different and often non-functional
protein product.
Nucleotide sequence repeat
expansion
• Results in extra copies of a particular
amino acid
• It may repeat so often that the gene
may be silenced and fails to express any
protein at all
• Fragile X syndrome
• Huntingdon’s disease
Fragile X syndrome
• Fragile X syndrome is a genetic
condition that causes a range of
developmental problems including
learning disabilities and cognitive
impairment. Usually, males are
more severely affected by this
disorder than females
• Fragile X syndrome occurs in
approximately 1 in 4,000 males
and 1 in 8,000 females
Huntingdon's disease
• Huntington's disease is an inherited disease
of the brain that damages certain brain
cells
• The disease damages some of the nerve cells
in the brain, causing deterioration and gradual
loss of function of these areas of the brain.
This can affect movement, cognition
(perception, awareness, thinking, judgement)
and behaviour.
Single nucleotide substitutions
include:
• A nonsense mutation is
the substitution of a
single base pair that leads
to the appearance of a
stop codon where
previously there was a
codon specifying an amino
acid. The presence of this
premature stop codon
results in the production
of a shortened, and likely
non-functional, protein.
Can result in sickle cell
disease and PKU
• A missense mutation is
when the change of a
single base pair causes
the substitution of a
different amino acid in
the resulting protein.
This amino acid
substitution may have no
effect, or it may render
the protein nonfunctional. Can result in
Duchenne muscular
dystrophy.
• Splice-site mutations occur
within genes in the non-coding
regions (introns) just next to
the coding regions (exons).
Before mRNA leaves the
nucleus, the introns are
removed and the exons are
joined together (splicing). A
mutation that alters the
specific sequence denoting the
site at which the splicing of an
intron takes place can 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 non-functional
protein. Can result in beta
thalassemia.
Beta thalassemia is a blood
disorder that reduces the
production of hemoglobin.
Hemoglobin is the ironcontaining protein in red
blood cells that carries
oxygen to cells throughout the
body.
In people with beta
thalassemia, low levels of
hemoglobin lead to a lack of
oxygen in many parts of the
body. Affected individuals also
have a shortage of red blood
cells (anemia), which can
cause pale skin, weakness,
fatigue, and more serious
complications. People with
beta thalassemia are at an
increased risk of developing
abnormal blood clots.
Chromosome Mutations
• Chromosome mutations occur during cell division,
both in mitosis or meiosis
• can cause a change in either the number or
structure of the chromosomes
• Deletion
• Duplication
• Translocation
• A mutation to a chromosome usually involves a
substantial change to its structure
• This type of mutation can be lethal
Deletion
• a segment of a
chromosome, and its
associated genes, is lost
• The effect depends on
exactly which sections of
DNA are lost and varies
from no effect to being
fatal
Deleted area
Example of Deletion Mutation
• The structure of a
chromosome can be
altered by:
– Deletion resulting in the
loss of a segment of the
chromosome
– Can result in Cri-du-chat
syndrome (deletion of
part of the short arm of
chromosome 5)
Another example of a Deletion Mutation effect
is ‘Williams Syndrome’
The name of this
syndrome is French for
"cry of the cat,"
referring to the
distinctive cry of
children with this
disorder.
Duplication
• The repeat of a
segment of a
chromosome
• Extra genetic
material is present
as genes are
repeated on the
same chromosome
• Can cause
detrimental effects
e.g. Cancer
Translocation
• Segments of 2
(or more)
chromosomes are
exchanged
• Or an entire
chromosome is
attached to
another
• E.g. chronic
myeloid
leukaemia
Part of
chromosome
22 has been
translocated
to
chromosome
9
This karyotype is from a woman with 45 chromosomes and a
translocation between chromosomes 13 and 14
No abnormal symptoms detected!
Chronic myeloid leukaemia
translocation (9;22)
• Chronic myeloid leukaemia
(CML) is a cancer of bloodforming cells in the bone
marrow. Abnormal cells
gradually fill the bone
marrow and spill into the
bloodstream. The disease
typically develops very
slowly and symptoms such as
anaemia, bleeding problems
or infections may not occur
for years after the disease
starts.
46,XYt(9;22)
Familial Down’s syndrome
• The vast majority of
Down’s syndrome cases
results from an extra copy
of chromosome 21,
however in about 5% of
cases one parent has the
majority of chromosome 21
translocated to
chromosome 14 resulting in
Familial Down’s syndrome
Chromosome mutations overview:
Mutations- you should know
• Mutations result in no protein or a faulty protein being expressed.
• Single gene mutations involve the alteration of a DNA nucleotide
sequence as a result of the substitution, insertion or deletion of
nucleotides.
• Single-nucleotide substitutions include: missense, nonsense and
splice-site mutations.
• Nucleotide insertions or deletions result in frame-shift mutations or
an expansion of a nucleotide sequence repeat.
• The effect of these mutations on the structure and function of the
protein synthesised and the resulting effects on health.
• Chromosome structure mutations – deletion; duplication;
translocation.
• The substantial changes in chromosome mutations often make them
lethal.