2 Mr. Jones's (2) Risk of Transmission of Genetic Disease Flashcards
Q: What are the 2 types of genetic disease? Give 3 features for each. (Inheritance, environment, occurrence)
A: Monogenic (defect of individual gene)
- Clear inheritance
- No environmental influence
- Individually rare
Complex Disorders
- No clear inheritance
- Environment essential
- Common
Q: List 3 examples of monogenic genetic diseases.
A: Huntington Disease, Cystic Fibrosis, Haemophilia
Q: List 3 examples of complex (disorders) genetic diseases.
A: Type 2 Diabetes, Schizophrenia, Crohn’s Disease
Q: What is Mendeleev inheritance?
A: The process whereby individuals inherit and transmit to their offspring one out of the two alleles present in homologous chromosomes
Q: What is an allele? What are different alleles described as? (2)
A: alternate forms of a gene or DNA sequence at the same chromosome location (locus)
Different alleles maybe described as MUTATIONS (not common in population) or POLYMORPHISMS (relatively common in population)
Q: What are Homologous Chromosomes?
A: matching (but non-identical) pair of chromosomes - one from each parent
Q: What is a mutation? What is a polymorphism? When are polymorphisms called mutations? Polymorphisms may contribute to?
A: Mutation - any heritable change in the DNA sequence
Polymorphism - a mutation at a >1% frequency in a given population.
Polymorphisms are usually still called mutations if they cause monogenic disease.
Polymorphisms may contribute to complex diseases
Q: What are the 2 main categories for mutations? Name 2 mutations within each?
A: Point Mutations:
- Missense - mutation means that the codon changes to code for a different amino acid.
- Nonsense - mutation means that the codon codes for a stop codon so the polypeptide chain ends prematurely.
Frame-shift Mutations:
- Insertion - insertion of an extra base will cause the code to be shifted out of frame.
- Deletion - deletion of a base
Q: What are frame-shift mutations also called?
A: Depending on what you consider a normal sequence, it can be either an insertion or a deletion. So they are sometimes referred to as InDel
Q: What are point mutations?
A: a single change in the DNA sequence
Q: Why should you take a family history? (5)
A: -identify genetic diseases in family
- identify inheritance patterns
- aid diagnosis
- assist in management of conditions
- identify relatives at risk of a disease (need to consider screening)
Q: Pedigree diagram. Square? Circle? Diamond? White? Black? Line from bottom left to top right? Number within? P within? Triangle? Arrow pointing at it?
A: male female unknown sex unaffected affected dead multiple pregnant miscarriage person giving info
Q: What are the 5 types of Mendelian inheritance patterns? Which are the main 3? Which 2 are sex linked? Which is rare?
A: 1 Autosomal Dominant
2 Autosomal Recessive
3 X-linked Dominant (RARE)
(4) X-linked Recessive
(5) Mitochondrial
3 and 4 are sex linked
Q: How do you draw a family pedigree? (4)
A: 1 build tree from bottom starting with affected person and siblings (inc names and DoBs)
2 one side of family (ask about their siblings and their children)
3 then other side
4 ask about chn with other partners
Q: In autosomal dominant inheritance, how many parents are affected? Which parent transmits it? Which sex child is affected? Transmission type? Carriers? Chance of being affected if one parent is affected? Expressivity?
A: at least 1
either
either
vertical transmission
don’t get carriers
50% (explained with punnet square)
varied (severity)
Q: Describe Huntington’s disease as an autosomal dominant disease. Main feature? Mean age of onset? Median survival time after onset? Treatment? Down the generations?
A: Motor, Cognitive and Psychiatric dysfunction - hyperkinesia
35-44
15-18
can ease symptoms but not cure
get genetic anticipation
Q: What is the 4 step Huntington’s disease mechanism? Not?
A: 1. HTT gene on Chr 4 encodes a protein called huntingtin.
- HD patient inherit one copy of a mutated form of the huntingtin gene.
- Altered gene encodes a toxic form of the protein that forms ‘clumps’.
- Cell death in basal ganglia of brain resulting in symptoms.
not loss of gene
Q: What is genetic anticipation? (2)
A: down the generations:
- age of onset decreases
- severity increases (also seen in myotonic dystrophy)
Q: What is the molecular basis of Huntington’s disease? (3)
A: Caused by an unstable triplet repeat (CAG)
Number of repeats may EXPAND with each generation
More Repeats = More Likely to be Affected
40-120 repeats = affected
35-40 = sometimes either way
Q: In autosomal recessive inheritance, how many affected parents are there? Which parent transmits it? Which sex child is affected? Family history? Risk of child being affected/carrier?
A: None
either
either
usually no family history
affected = 25%. carrier = 50%
Q: Describe cystic fibrosis as an autosomal recessive disease. (3) Treatment. How many people in UK are carriers?
A: -chronic, life threatening
- Thick mucus in lungs causes breathing problems and repeated infections.
- Blockages in pancreas affect digestive enzymes.
daily enzymes and physiotherapy
1 in 22
Q: What is the 4 step Cystic Fibrosis mechanism?
A: 1. CFTR gene on Chr 7 encodes a protein called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
- CF patients inherit two copies of mutated CFTR gene.
- Absence of functional CFTR protein affects chloride ion function in epithelial cells.
- Disruption of Salt/Water regulation causes thick mucus and leads to symptoms.
(absence of functioning protein causes disease)
Q: What is the molecular basis of cystic fibrosis? (3)
A: Most common mutation = delta F508
Deletion affects folding of CFTR protein and prevents it from moving to its correct place in the cell membrane
CF testing is part of UK newborn screening programme
Q: What is CAVD? Most cases are caused by?
A: Congenital Absence of the Vas Deferens (CAVD)
-condition in which the vasa deferentia fail to form properly -> Causes infertility
MOST CASES OF CAVD ARE CAUSED BY MUTATIONS IN THE CFTR GENE!
