Introduction: Genetics for

healthcare professionals

Dr Andrew Thomas
 APS4003/APS4015 Cell Biology & Genetics

Dr Andrew Thomas BSc PhD FRSB MBES
Sequenced the first piece of DNA
in Cardiff in 1987, published 50+ papers and proposed
the hypothesis of programmable DNA mutations.
Learning Outcomes
1. Explain the principles of genetic inheritance
in humans.
2. Describe the uses of genetic and
cytogenetic analysis in the identification of
human disease traits.
3. Solve basic genetic and inheritance
problems.

You will learn about;

• how genetic disease is inherited in humans in an autosomal, dominant and sex-

linked pattern.
• allele frequency and disease occurrence in population.
• Chromosomal abnormalities and changes in chromosome number.
 Why study genetics?
Genetics is the study of the inheritance of phenotypic traits such
as appearance, intelligence, genetic disease, behaviour etc.
• BMS – genetic disease e.g. cystic fibrosis
• Podiatry – phenotypic abnormalities and variations in
appearance e.g. nails
• SBN – sporting performance, fitness and predisposition to
injury and disease e.g. diabetes

In 2003 the Human Genome Project was completed – we now, not

only know the human genetic sequence, but we also have databases
for all the known genetic mutations that cause and contribute to
disease and health. This information is set to revolutionise medicine
and primary healthcare in the next 10-20 years.
 Genes are not alone: Our behaviour and the
interaction with our environment also affects our
health

e
as
Environment
Genes Di
se
 Are we at the mercy of our DNA code ?
Radiation

Age Diet

DNA
Exercise/training
Genes
Sex

Disease
Environment
Chemicals
How many of our traits are predetermined by the genetic code you inherited ?

Do genes determine whether we are extroverted or introverted or whether we are creative on not?

Does our genetic code influence our decision making ?

Can we override our genetic code ?

How much of an influence in the environment or our lifestyle on our genetics ?

What is Epigenetics? Epi = “on top of” our genome

The increasing importance of genetics in primary
healthcare

The scientific advances that have continued in the wake of the

Human Genome Project’s completion in 2003 are increasing
our understanding about the causes of genetically complex
common conditions such as asthma, diabetes, autism, bipolar
disorder and schizophrenia.
This offers new opportunities to diagnose disease more
accurately and to predict it ahead of any clinical manifestation.
We can now Identify population groups at increased risk which
help to target health promotion resources more effectively .
 Genomics in practice: diabetes
• At least seven different genetic subtypes of type 2 diabetes.
• These differ in terms of age of onset, pattern of hyperglycaemia, response to
treatment and association with other non-pancreatic effects.
• Recommend new disease classification based on the molecular genetic basis as it
gives a clearer indication of appropriate treatment:
For example,
• In the case of diabetes diagnosed before six months of age, infants with genetic
mutations affecting the ATP-sensitive potassium channel respond well to high
doses of sulphonylureas such as glibenclamide, rather than insulin.
• In familial, young onset diabetes, people with the HNF1A or HNF4A mutations
need low doses of sulphonylureas.

An understanding of the genetic aetiology of a disease enables more

appropriate treatment, better prediction of disease progression, screening for
family members and genetic counselling.

We are at the very start of the era of Pharmacogenetics

 What is Pharmacogenetics?
Pharmacogenetics is the study of how genes
affect a person's response to drugs.

Referred to as “Personalised Medicine” - In

other words – some drugs only work in certain
people and may actually cause more damage
than good.

It may be possible to predict the onset of

diseases and use drugs or life style
interventions to prevent or delay the onset of
a genetic disease e.g. CVD, diabetes ,
Alzheimer's etc

In 2003 it took 13 Yrs and $13 Billion to

sequence one human genome, we can now
sequence the genome of an individual in less
than a week for a few $1000.
 A Case Study in Pharmacogenetics:The use of
purine analogs in the treatment of leukaemia:

• 6-mercaptopurine, 6-thioguanine,
azathioprine
• Used to treat lymphoblastic
leukemia, autoimmune disease,
inflammatory bowel disease, after
transplant
• Interferes with nucleic acid synthesis
• Therapeutic index limited by 6-mercaptopurine 6-thioguanine

immune suppression side effect

azathioprine

• The drug is metabolized in the body

by an enzyme called thiopurine
methyltransferase or TMTP
Metabolism
of
6-Mercapto-
purine
Pharmacogenetics: A Case Study

Courtesy of Michelle Whirl-Carillo

Pharmacogenetics: A Case Study

Courtesy of Michelle Whirl-Carillo

Pharmacogenetics: A Case Study

Courtesy of Michelle Whirl-Carillo

What will you cover in genetics ?

• Mendelian genetics – Mendel’s two genetic principles and

how these are controlled by the process of meiosis i.e. cell
division used to produce sex gametes.
• Genetic inheritance patterns
• The concept of genetic inheritance and allelic
variation.
• The difference between recessive, dominant
and sex-linked disorders – examples of genetic
disease will be studied from each category.
• Co-dominant traits such as blood group.
• Genetic Linkage – certain traits can be inherited together
e.g. haemophilia and colour blindness.
• Allele frequency – prevalence of genetic disease in a
human ethnic group.
• Chromosomal abnormalities – including (a) variations in
chromosome structure and (b) changes in chromosome
number. Examples of different syndromes will be studied
• X Chromosome inactivation in females