Week 2 - A Day At The Genetics Clinic Flashcards
What gene is involved in Huntington’s?
HTT gene
What mode of inheritance is Huntington’s?
Autosomal Dominant
What mode of inheritance is cystic fibrosis?
Autosomal recessive
What mode of inheritance is muscular dystrophy?
X linked recessive
Which mode of inheritance requires that both copies of the same gene or alleles be the same in both heterozygous chromosomes?
Autosomal recessive
Which predominant mode of inheritance occurs in Mendelian diseases that affect mostly males
X linked recessive
What protein does the CFTR gene code for?
What is the function of this protein?
Cystic fibrosis transmembrane conductance regulator
Open and close chloride channels in lungs, pancreases, enterocytes which draws water into secretions
The CFTR protein is found in all membranes
Describe the type of mutations which affect the HTT gene and leads to the symptoms of Huntington disease
There is an increase in the number of CAG repeats in exon 1 of the HTT gene
10-35 repeats = pre mutation allele
36-39 repeats = variable penetrance
40+ repeats = 100% penetrance
How do mutations in the CFTR gene lead to the development of cystic fibrosis?
The CFTR gene regulates the opening and closing of chloride channels
Cl- moves along the electrochemical gradient
A faulty CFTR gene means Cl- does not move into secretion, water is not drawn into secretions and secretions are thicker and clog up the pancreas and lungs causing symptoms of cystic fibrosis (e.g. failure to thrive etc)
List TWO sources from which DNA samples can be obtained from an adult
Buccal smear (epithelial cells)
Blood sample
What is a trait called if it is controlled by only one gene?
Mendelian
Name some examples of autosomal dominant diseases?
Huntington’s disease
Marfan syndrome
Neurofibromatosis type 1
Polycystic kidney disease
Name some examples of autosomal recessive diseases
Phenylketonuria Tay Sachs disease Albinism Sickle cell disease Glycogen storage diseases
Name some examples of X linked recessive diseases
Haemophilia A and B
Hunter syndrome
Duchenne and Becker MD
Which part of the brain is effected in Huntington’s?
Cortex
Striatum
Which amino acid does CAG code for?
Glutamine
What are long repeats of CAG called in Huntington’s?
Poly-glutamines
Where is CFTR found?
In the epithelial cells of many organs including the lung, liver, pancreas, digestive tract, reproductive tract and skin
What causes the symptoms of Cystic Fibrosis?
CFTR is responsible for opening and closing chloride channels in the epithelial cells lining many organs including the lung, liver, pancreas, digestive tract, reproductive tract and skin
Because there is reduced chloride channels opening, secretions are thicker as water is not drawn into them, this results in clogging and the symptoms of cystic fibrosis
What are the different mutations you can have with Cystic Fibrosis?
As the CFTR protein is found in many different epithelial cells, you can have mutations in different places.
The mutation you have determines the severity of the disease and the mode of action of the disease
Examples are: - Class I CF mutations No synthesis of CFRTR Mutation: Nonsense, frameshift or splicing mutation that prevents CFTR biosynthesis) Genotype: G542X
- Class II CF mutations
Phenotype: Reduced trafficking
Mutation: CFTR is misprocessed in the ER, leading to an absence of functional protein at the cell membrane
Genotype: F508del - Class III CF mutations
Phenotype: Reduced gating
Mutation: CFTR protein reaches the cell membrane but once there it is unstable
Genotype: G551D - Class IV CF mutations
Phenotype: Decreased conductance
Mutation: CFTR protein reaches the cell membrane but abnormal conformation of the pore leads to disrupted ion flow
Genotype: R117H - Class V CF mutations
Phenotype: Reduced synthesis
Mutation: Reduced amount of CFTR protein at the cell surface due to reduced protein synthesis
Genotype: A455E
What is the phenotype, mutation and genotype of a Class I CF mutation?
Phenotype: No synthesis
Mutation: Nonsense, frame shift or splicing mutations prevent CFTR biosynthesis
Genotype: G542X
What is the phenotype, mutation and genotype of a Class II CF mutation?
Phenotype: Reduced trafficking
Mutation: CFTR is misprocessed in the ER, leading to an absence of functional protein at the cell membrane
Genotype: F508del
What is the phenotype, mutation and genotype of a Class III CF mutation?
Phenotype: Reduced gating
Mutation: CFTR protein reaches the cell membrane but once there is unstable
Genotype: G551D
What is the phenotype, mutation and genotype of a Class IV CF mutation?
Phenotype: Decreased conductance
Mutation: CFTR protein reaches the cell membrane but abnormal conformation of the pore leads to disrupted ion flow
Genotype: R117H
What is the phenotype, mutation and genotype of a Class V CF mutation?
Phenotype: Reduced synthesis
Mutation: Reduced amount of CFTR protein at the cell surface due to reduced protein synthesis
Genotype: A455E
What are the symptoms of cystic fibrosis?
- recurring chest infections
- wheezing, coughing, shortness of breath and damage to the airways
- difficulty putting on weight and growing
- jaundice
- diarrhoea, constipation or large, smelly poo
- a bowel obstruction in newborn babies (meconium ileus) surgery May be needed
Can also develop the following related conditions:
- diabetes
- thin and weakened bones (osteoporosis)
- infertility in males
- liver problems
Why does thick mucus cause the symptoms of cystic fibrosis?
The build up of sticky mucus in the lungs can cause breathing problems and increases the risk of lung infections (this can cause the lungs not to work properly over time)
Mucus can also clog up the pancreas which usually helps with digestion, this stops enzymes reaching the gut and helping with digestion
A lot of people with CF don’t absorb nutrients from food properly and need to eat more calories to avoid malnutrition
What are the symptoms of muscular dystrophy?
- sway back
- shoulders and arms are held back awkwardly when walking
- belly sticks out due to weak belly muscles (child is poor at sit ups)
- weak butt muscles (hip straighteners)
- thin, weak things (especially front part)
- knees may bend back to take weight
- thick lower leg muscles (the muscle is mostly fat and not strong)
- tight heel cord (contracture) child may walk on their toes
- poor balance: falls often (awkward clumsy if walking)
- weak muscles in front of leg cause foot drop and tip toe contracture
What is the age of onset of DMD?
2-5 years
What is the age of onset for Becker Dystrophy?
Late onset
8-10 years
Which is more common out of Duchenne’s and Becker’s?
Duchenne
What is the progression like for Duchenne’s and Becker’s?
Duchenne: Rapid
Becker: Slow
What is the intelligence level of patients with Duchenne’s?
Sub normal
What is the intelligence level of patients with Becker’s?
Normal
What is the life expectancy of someone with Duchenne’s?
15-20 years
What is the life expectancy of someone with Becker’s?
40- 50 years
What is a common associated symptom of Duchenne’s muscular dystrophy?
Cardiomyopathy
What is a common associated problem of Becker’s Dystrophy?
Colour Blindness
