Lecture 2- Genetic Transmission Flashcards
Contrast the characteristics of monogenic and complex disorders
- Clear inheritance vs no clear inheritance
- No environment vs environment essential
- Individually rare vs common
Give examples of monogenic disorders
Huntington’s
Cystic Fibrosis
Haemophilia
Give examples of complex disorders
T2D
Schizophrenia
Crohn’s disease
Define mendelian inheritance
- Process where individuals inherit and transmit to their offspring one out of the two alleles present in homologous chromosome
Define allele
Alternate forms of a gene or DNA sequence at the same chromosome location (locus)
Define homologous chromosome
- Homologous chromosomes are a matching (but non-identical) pair
- One inherited from each parent
Define ‘mutation’
Any HERITABLE change in the DNA sequence
Define ‘polymorphism’
A mutation present in >1% of a population–> complex disease
What are the two classes and four subclasses of mutations?
1) Point Mutation
- Missense: Change in codon to code for different amino acid
- Nonsense: Change in codon that codes for stop codon= premature end of polypeptide
2) Frameshift Mutation
- Insertion: insertion of extra base causing the code to shift out of frame
- Deletion: deletion of a base
What is a point mutation?
A single change in the DNA sequence
What does a triangle represent in a pedigree diagram?
Miscarriage
If you have a small arrow pointing to the square or circle, what does it represent?
The person providing the pedigree information
What is consanguineous mating and how is it displayed on a pedigree?
Marriage with blood relative
A double line
What are the five types of mendelian inheritance patterns?
1) Autosomal dominan
2) Autosomal recessive
3) X-linked dominant
4) X-linked recessive
5) Mitochondrial
Give an example of an autosomal dominant disease
Huntingtons’s disease
What are the symptoms of Huntington’s disease and what is its mean age of onset?
- Motor, cognitive and psychiatric dysfunction
- hyperkinesia
- Mean age of onset 35 to 44 years
Which gene and protein is involved in Huntington’s disease?
HTT gene on Chr4
Huntingtin protein
What does the mutated gene cause?
- Toxic form of huntingtin that forms clumps
- cell death in basal ganglia
What does it mean by the ‘genetic anticipation’ of Huntington’s?
As you go down generations:
- age of onset decreases
- severity increases
What causes the genetic anticipation of Huntington’s disease?
- Huntington’s Disease is caused by unstable CAG triplet repeats.
- As you go down generation # of repeats increases (>40 repeats for disease)
Give an example of an autosomal recessive disease
Cystic Fibrosis
Which gene and protein is involved in cystic fibrosis?
- CFTR gene on Chr7
- CF transmembrane conductance regulator protein
What happens when you have a mutation on the CFTR gene?
- affects Cl- ion channel function in epithelial cells
- Disruption of Na+/ H2O regulation –> thick mucus
What are the symptoms of CF?
- breathing problem, infection (caused by thick mucus in lungs)
- Blockages in pancreas affects digestive enzymes
What is the most common mutation causing CF?
Delta F508 (deletion of Phe @ aa 508)
Name another condition caused by a mutation in the CTFR gene and give some of its symptoms
- Congenital absence of the vas deferens (CAVD) –> vas deferent fail to form properly
- -> azoospermia (infertility)
What are the characteristics of X-linked recessive disorders?
- No affected parents
- Transmitted by carrier F
- Only males affected
Give an example of an X-linked disease
Haemophilia
What causes haemophilia A?
- Mutation of F8 gene on ChrX
- Loss of functioning Coagulation Factor VIII
What causes haemophilia B?
- Mutation of F9 gene on ChrX
- loss of functioning coagulation factor IX
Give examples of genetic heterogeneity
1) Same gene, different mutation, different symptoms- cystic fibrosis and CAVD caused by mutation in the CFTR gene
2) Same disease, different gene- Haemophilia A/B
3) Same disease, different genes, different inheritance patterns- Epidermolysis Bullosa (AD/ AR)
Define incomplete penetrance
Symptoms not always present in an individual with a disease causing mutation
Define variable expressivity
Disease severity may vary between individuals with the same-disease causing mutation
Define phenocopy
Having same disease but with different underlying caus
Define Epistasis
Interaction between disease gene mutations and other modifier genes which affects phenotype
Look at the molecular mechanisms of dominant, recessive and co-dominant conditions
1) Dominant- presence of toxic protein- effects of mutated gene mask normal copy
2) Recessive- absence of functional protein- effects seen when normal copy is absent
3) Co-dominant- both mutated and normal genes apparent (e.g. sickle cell trait)
What is the therapy for dominant and co-dominant conditions?
- Neutralise the effects of the toxic protein
- ‘switch off’ the mutant gene
What is the therapy for recessive conditions?
- Restore activity of the missing protein
- replace the gene/ protein/ affected tissue
