Topic 2 - Genes and Health

Gene definition

A sequence of baes which codes for an amino acid sequence
A sequence of amino acids which determines protein structure and function

Genes as…

Causal factors and diagnostics tools

Genes as causal factors

Inherited mutations, or mutations more generally, can cause disease

Genes as diagnostic tools

Can screen to see whether a person will get a disease/disorder
Can be used for personalised medicine

Examples of genetic disorders

Cystic fibrosis
Huntington's disease
Sickle cell anaemia
Haemophilia
Colour blindness
Albinism
Down's syndrome

What happens in sickle cell anaemia

Red blood cells are sickle shaped
Due to a mutation (genetic difference) caused by a recessive allele
Caused by abnormal Hämoglobin
RBCs become rigid, sticky and crescent-shaped
Affected cells have a much shorter lifespan than normal cells - only 10-20 days rather than 3 months - people need to eat more iron due to a higher demand
Can become stuck in small blood vessels, cutting off oxygen supply to downstream organs
A heterozygote would be partially affected due to incomplete dominance

Sickle cell anaemia: why still around?

Natural selected hasn't gotten rid of the allele for sickle cell anaemia, so it must have some use
There are many cases or sickle cell anaemia in Africa, and many malaria cases

• in malaria, you are bitten by a mosquito carrying the malaria parasite which enters your blood. The parasite enters the RBC and reproduces a lot.
• at some point, the RBCs burst open, releasing parasites into the bloodstream
  However, the parasite for malaria doesn't recognise the sickle cells, so people with SCA aren't harmed
  Heterozygote advantage!!!!

CF: what is it?

Genetic disorder caused by a recessive mutation
Suffered produce a thick, sticky mucus that is unable to be moved effectively by cilia
The sufferers are at more of a risk of contracting lung infections as mucus isn't moved, so pathogens aren't destroyed
Affects other mucus-producing areas of the body too, such as the digestive system and reproductive tract

CF+TB

In populations with high numbers of CF carriers, there are low TB incidence rates, as it offers some protection
Heterozygote advantage!!

CF: severe tiredness

Mucus lines the lungs of sufferers, so the lungs' surface area is smaller, meaning less oxygen can be taken into the bloodstream per breath
This means organs get less oxygen - hypoxia- leading to severe tiredness

CF medication: pulmozyme -"dornase Alfa"

Helps to break down the mucus
Due to stationary mucus, bacteria and infections colonise, leading to the acculturation of neutrophils in the affected area
After the initial response, the neutrophils die, leading to increased amounts of highly polymerised DNA in the mucus, leading to further mucus thickening
Dornase alfa cleaves extracellular long-chain DNA, making the mucus less viscous, think and sticky

Consequences of CF

Respiratory system

• greater risk of lung infections as mucus
• shortness of breath

Digestive system

• impaired digestion
• pancreatic damage

Reproductive system

• reduced fertility as sperm struggle to leave

Sweat glands

• sweat becomes extremely salty

View into the trachea: what do you see

Oesophagus: expands into the trachea when you swallow
Smooth muscle: used in cough reflex - it is where it is so that the oesophagus can expand when you swallow food
Cartilage ring: keeps the trachea stable + open - prevents the trachea from collapsing in onto itself when breathing

Main respiratory symptoms of CF

Increased rate of lung infection
Shortness of breath

Physiological meaning

How body systems work/function

CF physiological abnormality

Production of think, dry, sticky mucus which lines the airway

Why do we have mucus

our airways produce mucus as mucus traps pathogens and other foreign substances at entrances to the body, preventing then from further entering the body and leading to harm
Defense against disease

why do CF sufferers have thicker mucus than normal

The faulty CFTR gene prevents cells from moving salt and water properly across cell membranes, leading to a deficit in water in the mucus, making it thick and sticky

Why is thicker mucus dangerous

Thicker mucus leads to an increased risk of lung infection, as the pathogens are trapped and mot moved away, but can grow and proliferate in the airways, leading to lung infections

Mucus production in the airways

Mucus is produced by goblet cells
Goblet cells are found between ciliated epithelial cells in the trachea, bronchi and bronchioles only

Parts of airway mucus production

Cilia
Goblet cells
Mucus
Columnar epithelial cells
Basal membrane

how is mucus moved along the airways

Mucus is moved by cilia
It is called the muco-ciliary escalator
Mucus is moved to the throat

What is mucus as a substance

A viscous colloid

what is a colloid

a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance

What does mucus consist of?

90% water
3% mucins
2% other stuff (glcoproteins, lipids, DNA)

What are mucins

a group of proteins with a relatively high molecular weight
Able to form gels in water, to become sticky

Important organelles in goblet cells

ER
Golgi apparatus
Ribosomes
Mitochondria
Pronounced nucleus

Function of the ER

a network of paths and tubes in the cell. ribosomes line the surface of the ER. when a protein is made, it gets pushed into the tubes to the golgi apparatus

Function of the golgi apparatus

responsible for protein folding and packaging

What is a tissue

a group of the same type of cells working together to carry out a function. organs consist of lots of different types of tissue

Simple tissue

one layer of cells

simple squamous epithelial tissue

found in the alveoli and capillaries
found where molecules need to diffuse through

simple cuboidal epithelial tissue

-lines kidney tubules and glands
-secretes and reabsorbs water and small molecules
-cells are shaped like cubes
-found in the kidney tubules
-found in places where active transport is needed

simple columnar epithelial tissue

-lines most digestive organs (stomach and intestines)
-absorbs nutrients, produces mucus
-have cilia often
-tall and thin
-found in the bronchiole, ciliated epithelium and intestines

stratified tissue

made from several layers of cells

stratified squamous epithelial tissue

-outer layer of skin, mouth, and vagina
-protects against abrasion, drying out, and infection

stratified cuboidal epithelial tissue

-lines ducts of sweat glands
-secretes water and ions
-many layers of cube shaped cells
-rare

stratified columnar epithelial tissue

protection secretion, very rare,
found in male urethra, and conjunctiva

where is mucus produced

pseudostratified columnar epithelial tissue

pseudostratified columnar epithelial tissue

in the trachea and bronchii
technically simple, but looks stratified
produces the mucus

why do CF sufferers have a higher risk of lung infections?

mucus traps bacteria in airways
in CF, the mucus is too thick to be moved by the muco-ciliary escalator
the oxygen levels in mucus are low, so anaerobic bacteria thrive
WBCs are attracted to fight bacteria
WBCs die - the remains of the cell release their contents, including DNA, increasing the stickiness of the mucus
overall, increased inflammation and infection risk

why do CF sufferers often experience shortness of breath?

mucus blocks airflow through bronchioles
less air reaches alveoli
reduced gas exchange

gas exchange def

the movement of oxygen and carbon dioxide in opposite directions by diffusion across a cell membrane

diffusion def

the passive movement of particles from an area of high concentration to an area of low concentration down a concentration gradient

why is diffusion passive

requires no metabolic energy from the cell

what is a concentration gradient

the different in concentration between two places

factors affecting rate of diffusion

concentration gradient
surface area
diffusion distance
temperature
molecular size

effect of an increase in concentration gradient on rate of diffusion

greater gradient = faster diffusion

effect of an increase in surface area on rate of diffusion

greater surface area = faster diffusion

effect of an increase in diffusion distance on rate of diffusion

greater distance = slower diffusion

effect of an increase in temperature on rate of diffusion

greater temperature = faster diffusion

effect of an increase in molecular size on rate of diffusion

larger molecules = slower diffusion

which factors affecting diffusion are our of control of living systems

temperature and molecular size

Fick's law: what does it describe

it describes the relationship between the three key factors influencing diffusion rate in living systems

Fick's law

rate of diffusion = (SA * difference in concentration) / diffusion distance

what does Fick's Law state

rate of diffusion is proportional to concentration gradient and surface area
rate of diffusion is inversely proportional to thickness of gas exchange surface

FIck's law: size in biology

size really matters in biology
bigger cells can command more resources from their environment
they are better protected against environmental change than smaller cells

why haven't cells evolved to become massive?

bigger cell shave greater metabolic demand. e.g greater oxygen intake and carbon dioxide removal
how much they need is determined by volume: a bigger cell has a greater volume and thus needs more oxygen to sustain its respiration
however, the rate at which they can take oxygen into their cytoplasm is determined by their surface area
as cells increase in size, volume increases faster than surface area

key structures of the alveoli

terminal bronchiole
alveolar epithelium
capillary endothelium
red blood cells
plasma

what is secreted by the alveolar epithelium

moisture, including surfactant

what is surfactant

surfactant is a detergent-like substance make from phospholipids

what are phospholipids

phospholipids are a lipid derivative
they consist of hydrophobic and hydrophillic regions
these molecules disrupt surface tension and prevent adjacent water molecules from sticking together
this means that alveoli don't stick themselves together
phospholipids are also vital in forming cell membranes

Mucus + airways in CF

Sticky mucus blocks airways

How is mucus production controlled

Mucus production is controlled by transport proteins in the membranes of goblet cells

Transport proteins in CF patients

Transport proteins in CF patients are missing one amino acid

Location of coding for the protein of the missing amino acid in CF

Found at position 7q31.2 in the human genome

Structure of a chromosome from top -> bottom

p arm (shorter one)
Centromere
q arm

Where is the CFTR gene found?

Chromosome 7
q arm (long arm)
31.2 (no. of thousand bases it is below the centromere

What does CFTR stand for

Cystic fibrosis transmembrane reductase

what is the structure of something

how something is constructed

what is the physiology of something

how something works

what structural and physiological factors combine to make gas exchange in alveoli so efficient

diffusion distance
concentration gradient
surface area

efficient gas exchange in alveoli: diffusion distance

as short as possible
only two cells separate the alveolar air space and blood
alveolar epithelium is very thin, due to simple squamous tissue
narrow capillary lumen (8 micrometers)

efficient gas exchange in alveoli: concentration gradient

maintained to be as large as possible because of repeated ventilation and constant blood flow

efficient gas exchange in alveoli: surface area

alveoli are extremely numerous and very small

oxygen in atmospheric air

21%

how much of inhaled air in the alveolus contains oxygen

about 13%

why does atmospheric air contain 22% oxygen, but inhaled air in the alveolus only contains 13% oxygen

when you inhale, atmospheric air mixes with 'old' carbon dioxide-rich air already in the alveolus
this air is called residual air

how does CF affect alveolar efficiency

blockage of bronchioles
alveoli can fill with mucus
feeling short of breath

how can blockage of bronchioles affect alveolar efficiency

blockage of bronchioles means that air cannot reach all the alveoli in the lungs
this means that the effective surface area is reduced

how can alveoli filling with mucus affect alveolar efficiency

diffusion distance is increased

how can feeling short of breath affect alveolar efficiency

feeling short of breath can lead to increased breathing effort
this can lead to overexertion of lungs
long-term over-inflation can reduce the elasticity of the lungs, which in turn means less efficient exhalation
this ultimately means that the concentration gradient is reduced, so gas exchange is less efficient

what are proteins

polypeptides (amino acid chains)
proteins are polymers
chains of amino acids

what does the amino acid sequence determine and what is it determined by

amino acid sequence is determined by the DNA base sequence
amino acid sequence determines the overall structure of the protein

examples of proteins

enzymes
haemoglobin
hormones
muscle fibres

amino acid structure
different groups

all amino acids share the same fundamental structure

amino acids in biological systems

in biological systems, amino acids exist as zwitterions
amino acids don't dissociate in water
molecules with both positive and negative charges on different parts of the molecule

which part of the amino acid ion is positive and which is negative

the COOH part loses a H+ and becomes negative
the NH2 part gains a H+ and becomes positive

How does charge distribution affect bond formation in amino acid ions?

The charge distribution makes it energetically favorable to form bonds between adjacent amino acids.

What can the two ends of an amino acid molecule do to buffer pH?

The two ends can either accept or donate protons.

protein unique structures and functions: caused by what

the interaction of R groups

what are R groups

residual groups

what is the R group part

the R group is the part of each amino acid that makes it unique

how many different types of R groups

20 different R groups, so 20 different amino acids exist

how can R groups vary

vary in size, polarity and charge

polar side chain

the R-group of an amino acid that contains electronegative atoms like oxygen or nitrogen, creating an uneven electron distribution and resulting in a partial charge.

what is a non-polar side chain

the part of an amino acid that consists primarily of hydrocarbon groups (carbon and hydrogen atoms) and is therefore hydrophobic, meaning it repels water

what are essential amino acids

amino acids which you cannot synthesise yourself

how do two amino acids react
what is the product
how do they join
what is produced
what reaction is it

two amino acids react forming a dipeptide
one amino acid loses the OH from COOH and the other amino acid loses the H from the NH2
the C from the one amino acid joins with the N from the other amino acid
water is also produced
this is called a condensation reaction

condensation reaction

joining molecules together in biology happens through a condensation reaction and produces water as a waste