Inherited diseases To show examples of diseases

inherited through dominant and recessive alleles.

To be able to correctly predict the outcome of various combinations of parent genotypes.

Huntington’s Disease Mental degenerative disease; Develop uncontrolled movements Develop form of dementia Lose ability to swallow Often associated psychological

problems Onset usually in middle age 30 - 40 Can be early < 20 or later Death occurs within 20 years of onset Usually faster in younger sufferers

Inheritance It is autosomal dominant Need only one allele from one parent If you have the gene you will inherit the

disease; Can get worse from generation to

generation Especially if carrier is father Some people have only very mild version

with no obvious signs Thus a person with no family history can

develop the disease

Pathology Mutant gene affects the production of a protein

called Huntingtin; Role of Huntingtin in body not well understood;

mostly present in brain and testes Interacts with proteins involved in transcription,

cell transport and cell signaling May be important in gene transcription and the

development of nerve cells especially in embryos

Mutant Huntingtin damages the nerve cells in the brain gradually causing the development of symptoms

Genetics Huntingtin gene has multiple repeats of

the trinucleotide CAG Mutant gene has extra repeat segments The resulting disease status, depends on

the number of CAG repeats <28 Normal Unaffected 28–35 Intermediate Unaffected 36–40 Reduced Penetrance +/- Affected

>40 Full Penetrance Affected >60 Onset before age of 20

What this means An unmutated gene has less than 28

– most people Full penetrance means you will have

it and have a 50% change of passing it to your child

Intermediate will either be weak and very late onset or not at all

Often not noticed

Passing it on Gene is unstable Especially in spermatogenesis it can

get longer How is this relevant to which parent

has it? How might this affect families with

intermediate genes?

Prevalence 5 – 10 cases per 100 000 people world

wide Much commoner in people of western

European origin – mixed race 7 per 100 000

Very rare in Asians and Africans 0.1 per 100 000

Clusters in certain isolated populations: Lake Maracaibo Venezuela, 700 per 100 000.

Treatment and Cure No cure Treatment can alleviate symptoms Some medications to reduce

involuntary actions Some mediations to tackle

psychological issues.

Cystic Fibrosis Also known as mucoviscidosis (sticky mucus) Developmental disease Lungs do not develop properly Digestive system does not absorb food Pancreas stops functioning Observed in infancy Untreated leads to very early death Treated increases survival but likely to

reduce growth Some people seem very healthy Others seriously compromised

Complications Many respiratory infections Poor growth due to malnutrition Diabetes due to damage to pancreas Intestinal blockage in newborns Sterility due to blockage of sperm

duct (sperms fine) Cirrhosis of the liver

Inheritance This is a recessive disease This means you must have both

alleles to have the disease; If you have one allele you are a

carrier and do not show the disease; Both parents must be carriers for a

child to have a disease Chance of having disease is 1 in 4

Pathology CF is caused by a mutation in the

gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR);

This protein regulates the components of digestive juices, sweat and mucus;

Only one healthy gene is needed for this to function

Genetics There are over 1500 possible

mutations to the CFTR gene that can lead to CF

Over 60% of cases worldwide are due to one specific mutation;

Screening usually tests for up to 32 different mutations, but this does mean that some cases can be missed by screening.

Prevalence Commonest in western European

Caucasians (1 in 25 are carriers) Highest prevalence in Ireland Non European populations much rarer and

usually a different mutation (1 in 46 Hispanics in US, 1 in 65 African Americans)

In 1959 median age of survival was 6 months

The median survival age in Canada has increased from 24 in 1982 to 47.7 in 2007

Treatment and cure Possible cure through introduction of gene to

airways – early stages Treatment of lung diseases through antibiotics Preventative use of antibiotics Physiotherapy to help clear lungs of fluid Replacement of digestive enzymes (pills) Insulin Healthy diet and exercise May need lung, liver and pancreas transplants Assisted reproduction

Prevention At risk adults may get genetic testing. Expensive so usually only one parent done at

first (many mutations screened for) Pre-implantation genetic diagnosis Testing of foetus in utero by amniocentesis or

chorionic villus sampling of placenta Screening of new born: test sweat Parents may notice baby tastes salty Worst option wait till respiratory

complications and poor growth show; Best prognosis with earliest diagnosis

Amnioscentesis

Carries a risk of about 1 in 200 of initiating an abortion

Ethics What ethical issues surround the

following decisions 1. To start a family 2. To test foetuses 3. To decide against having a child 4. Gene testing and medical records

Homework Research another genetically

inherited disease It must be dependent on one gene –

rules out diabetes, heart disease and breast cancer which only have genetic links

Write a two page report on the disease

Follow rubric for guidance

Inherited disease rubric 1. Description of disease 3 points 2. Explanation of inheritance 5 points 3. Treatments, cures and preventions 4

points 4. Spelling and grammar 3 points (<10

mistakes = 3 points, 10 – 20 = 2 points, >20 = 1 point)

Presentation (5 points): intelligently chosen visual material (2) Captions(1), Subheadings, (1) references (1)