Week 1 - Genetics Flashcards
Which gene is involved in Hungtinton disease?
Huntingtin (HTT)
How many CAG repeats in the Huntingtin gene is normal?
10-35
How many CAG repeats in the Hungtintin gene are associated with Huntington’s disease?
36-120
Which type of genetic transmission is susceptible to gene expansion during meiosis in Huntington disease?
Paternal
What is genetic antisipation?
Expansion of gene mutation during meiosis, leading to increased severity and age on onset in subsequent generations
How does a mutation in the huntingtin gene cause the symptoms of Huntington’s disease?
Gene codes for a polyglutamine tract
Expansion of tract causes insoluble protein aggregates which lead to neurotoxicity
What are the main symptoms of myotonic dystrophy?
Progressive muscle weakness in early adulthood
Myotonia
Cataracts
Which gene is mutation in myotonic dystrophy and what is the nature of the mutation?
DMPK gene
Unstable length mutation of CTG repeat in 3’ region (50 or more repeats)
Which type of transmission more commonly causes expansion in myotonic dystrophy?
Maternal
What effect does mutation of the DMPK gene have?
Indirect toxic effect upon spicing of other genes such as the chloride ion channel (causing myotonic)
What is a common complication of CF? (other than lung infections)
Exocrine pancreas insufficiency
How is CF diagnosed?
Screening of newborns (heel prick) by immunoreactive trypsin (IRT) level
DNA testing for CF mutations
Sweat testing for increased chloride concentration
Which gene is mutation in CF?
CFTR
What effect does a mutated CFTR gene have?
Defective chloride ion channel causing increased thickness of secretions
What is the most common mutation in CF?
F508del
What are the clinical features of NF1?
Cafe au lait macules Neurofibromas Short stature Macrocephaly Learning difficulties
Which conditions are patients with NF1 at increased risk of?
Hypertension
Scoliosis
Pathological tibial fractures
Tumours
What type of inheritance is Duchenne Muscular Dystrophy?
X-linked recessive
What type of inheritance is NF1?
Autosomal dominant
What is the function of dystrophin?
Forms link between F-actin intracellularly and the dystroglycan complex
What is creatine kinase?
Protein that leaks out of damaged muscle fibres into the blood
What is often the first sign of DMD in boys on investigation?
High serum creatine kinase
What is the difference between DMD and BMD?
Age of onset - 3 in DMD, 11 in BMD
Disability - wheelchair by 12y in DMD, much later in BMD
Deletion mutation - out of frame in DMD, in frame BMD
By what manner is fragile X syndrome inherited?
X-linked recessive
What causes genetic anticipation in Fragile X Dyndrome?
Repeats in the 5’ region of FMR1 gene
What is the consequence of an expansion >200 repeats in the FMR1 gene? (Fragile X)
Severe phenotype in males
Carrier females mildly affected
What are the complications of Down syndrome?
Learning difficulties
Heart malformations
Hypothyroidism
What is Edwards Syndrome?
Trisomy 18
What are the clinical features of Edwards Syndrome?
Small chin
Clenched hands
Malformations of heart and kidney
Profound learning difficulty
What is Patau Syndrome?
Trisomy 13
What are the clinical features of Patau syndrome?
Cleft palate Microphthalmia Abnormal ears Clenched firsts Extra little finger
At what stage in fertilisation is PGD performed?
Day 3 when embryo 6-10 cells
What are the cons of PIGD?
Long wait
Not available to all women
Multiple visits and procedures
Take home baby rate around 50% per cycle
What conditions is embryo sexing used to prevent?
X-linked recessive
How do you calculate the sensitivity of a screening test?
TP/(TP+FN)
How do you calculate the specificity of a screening test?
TN/(FP+TN)
What is used to screen for DS in 1st trimester?
Combined Ultrasound and Biochemical Screening (CUBS)
What does CUB consist of?
Maternal blood biochemical markers
Ultrasound looking for increased nuchal translucency
Give examples of conditions that can be screened for in neonates by the heel-prick test
Phenylketonuria MCADD Congenital hypothyroidism CF Sickle cell disorder
Name a disease that is screened for in Jewish people
Tay Sachs
Name 2 invasive prenatal screening tests
Chorionic villous sampling
Amniocentesis
What is NIPT?
Non-invasive prenatal testing on maternal plasma for free fetal DNA
What is NIPT used for?
Sex determination in X linked conditions
Paternal mutations e.g. FGFR3
Aneuploidy
What condition is ivacaftor used to treat?
CF
Which mutation must a patient have to receive ivacaftor?
G551D
What is the function of ivacaftor?
Mutation blocks the opening of CFTR chloride ion channels
Ivacaftor reopens the channel
Which drug is used to treat lung cancer with a EGFR mutation and what is it’s mechanism?
Gefitinib
Tyrosine kinase inhibitor
Which drug is used to treat HER2 positive breast cancer?
Trastuzumab (Herceptin)
Describe a possible future therapy for DMD
Use exon skipping to convert DMD to BMD phenotype by altering the splicing patterns to correct the reading frame
Name 2a drugs that may be used in DMD
Ataluren
