Genetic conditions Flashcards
How many genetic conditions are estimated to exist?
4000-6000
What is defined as a ‘rare disease’ in the UK?
one that affects 1 in 2,000 or less of the population
How many people in the UK will be affected by a rare disease at some point in their life?
1 in 17 (3 million)
What percentage of newly diagnosed cases of rare diseases are in children?
50%
How many different rare diseases exist?
5000-8000
What percentage of rare diseases have a known genetic origin?
80%
What is genetic counselling?
a role that is developing alongside those within genetics
supports patients and families in understanding their health and the impact genetics may have on treatment options
What is CRISPR-Cas9?
a genome editing tool that allows the removal and replacement of certain DNA
used in personalised medicine to advance patient care and even cure inherited diseases
What does CRISPR stand for?
clustered regularly interspaced short palindromic repeats
What are the two components of CRISPR?
Cas9 protein - cuts DNA
guide RNA - recognises the DNA sequence to be edited
What are the stages involved in the use of CRISPR-Cas9?
(1) scientists identify the sequence of the human genome that causes a health problem
(2) scientists create a specific guide RNA (gRNA) to recognise the DNA sequence
(3) gRNA is attached to Cas9 and the complex is introduced to the target cells
(4) it locates the target letter sequence and cuts the DNA
(5) at this point, scientists can edit the existing genome by modifying/deleting/inserting new sequences
What are the two types of mutations?
germline - occur in sperm and egg cells and inherited from the mother or father
somatic - occur in any other cell type and not inherited
When mutated, which genes are involved in the development of breast cancer?
BRCA1 (chromosome 17) and BRCA2 (chromosome 13)
usually inherited
What does BRCA stand for?
breast cancer suppressor gene
Besides breast cancer, BRCA mutations are linked to an increased risk of which other cancers?
ovarian, pancreatic, prostate
Who should be made aware of and undergo genetic testing?
strong family history of cancer
a relative with a known BRCA mutation
Why is it important to know your BRCA-mutation status?
patient can make an informed decision and proactively address cancer risk and the risk to family members as well as any future treatment decisions
What are the two types of test to detect a BRCA mutation?
(1) blood/saliva - to examine the presence of germline mutations
(2) tumour testing - breast biopsy to examine the presence of germline and somatic mutations (unidentifiable in a blood/saliva test)
What factors need to be considered before a patient undergoes genetic testing?
risks and benefits (many implications of knowing genetic status)
How many genes have been identified as being potentially involved in the development of multiple sclerosis?
over 200
Why is MS not passed directly from parents to children?
it is not caused by a single gene
What is the chance of a person developing MS if they have one parent with MS?
1 in 67
What is the chance of a person developing MS if they have a sibling with MS?
1 in 37
What is the chance of a person developing MS if they have an identical twin with MS?
1 in 5
What proportion of the population have inherited familial hypercholesterolaemia (FH)?
1 in 250
What causes FH?
the sufferer inherits a gene mutation in the LDL receptor from one parent
What is homozygous FH?
the sufferer inherits the gene mutation from both parents
more severe form of FH
What factors could suggest a diagnosis of FH?
total cholesterol level >7.5 mmol/L (should have fasting blood test to measure LDL cholesterol)
family history of heart attack under the age of 60
What lifestyle factors can help to reduce cholesterol levels?
heart healthy diet
regular exercise
maintain a healthy weight
avoid smoking
Why are statins the first-line treatment for most patients with FH?
safe and effective
slow down cholesterol production
What treatment is available for patients who do not respond to the best available medication?
injectable therapies
What treatment is available for patients with homozygous FH?
medication to slow down LDL production
How many genetic mutations have researchers found to occur commonly in patients with rheumatoid arthritis (RA)?
over 100
Which two genes are particularly associated with RA?
HLA-DRB1 gene and protein tyrosine phosphatase 22 (PTPN22) gene
What is the HLA-DRB1 gene?
the strongest known genetic risk factor for RA
there are many different variants of this gene and several are associated with an increased risk of RA
some evidence of an interaction between certain variants of the gene and environmental factors
the risk of developing RA is increased in smokers and who also have certain high risk HLA-DRB1 variants
What is the PTPN22 gene?
unclear exactly how this gene predisposes to autoimmune disease
known to be associated with an increased risk of developing RA
What is the prevalence of cystic fibrosis (CF) in the UK?
10,500
What proportion of people carry the gene for CF with no symptoms?
1 in 25
What is the chance of being born with CF if both your parents carry the gene?
1 in 4
What causes CF?
a faulty gene that disrupts the movement of salt and water in cells
this makes mucus thicker and stickier
sticky mucus affects lungs and digestive system
airways become clogged up with mucus causing infection and damage over time
What are some of the main symptoms of CF?
frequent chest infections severe coughs shortness of breath abnormal bowel movements difficulty gaining weight infertility (for most men)
Why should people with CF never meet each other?
infections that are transmitted between people with CF cause illness
What is the treatment for CF?
medication (sometimes more than 40 tablets per day) - to thin mucus
antibiotics - to kill bacterial infections in the lungs
enzyme capsules - to take with food
high-fat diet - to ensure the body receives sufficient nutrients
physiotherapy - to move the mucus that builds up around the organs
lung transplant - if conventional treatments are no longer effective
What causes Crohn’s disease?
a combination of genetic, environmental, and lifestyle factors, many of which are unknown
many genes related to the disease, including NOD2, ATG16L1, IL23R, and IRGM, are located on chromosomes 5 and 10, which are involved in immunity
not inherited but appears to run in some families (present in more than one relative in 15% of cases)
