Genetic diagnosis 1 (Lucy) Flashcards
What ar ethe 4 types of genetic diseases that can arise from point mutations?
- Cystic fibrosis
- Phenylketonuria
- Achrondoplasia
- Osteogenesis imperfecta
What type of disease is cystic fibrosis?
Loss of function, recessive
What type of disease is phenylketonuria?
Loss of function, recessive
What type of disease is Achrondoplasia?
Gain of function, dominant
What type of disease is osteogenesis imperfecta?
Loss of function, dominant negative
What are the main clinical symptoms of CF?
- Chronic pulmonary disease
- Pancreatic exocrine insufficiency
- Hepatic disease (liver)
- Intestinal abnormalities
- Infertility (urogenital abnormalities in males)
Why so much focus on CF?
Most common life threatening disease in the UK
1 in 23 carry mutated CFTR gene (>2 million ppl)
Affects over 8000 ppl in the UK
43% of ppl w CF have diabetes
What is the most common mutation in CF?
ΔF508
What is ΔF508?
3bp deletion –> maintains fram but removes phenylalanine
How many reported mutations are there in the CFTR gene?
Over 1000
What is the mutation in PKU?
Splice site IVS12+G>A
Or missense = F39L or I65T
What is affected in PKU?
The PAH enzyme
Has 21 exons over 80kb
Recessive disease - 2 mutations needed for phenotype
What is the mutation called in ACH?
1138G>A
What gene is affected in achondroplasia (ACH)?
FGFR3 gene
Occurs at a CpG site (G to A mutation)
What is the amino acid change in ACH?
Gly380Arg
What sort of disease is Alpha-thalassamia
Loss of function –> recessive
What does the muation in Osteogenesis imperfect affect?
Collagen production
It is a dominant negative effect
What is the genes affected in Osteogenesis imperfecta?
COL1A1 & COL1A2
(These code for type 1 procollagen)
What is type 1 procollagen?
Made up of 3 amino acid chains encoded by COL1A1 and COL1A2
What does a null mutation in either COL1A1 or COL1A2 cause?
Mild osteogenesis imperfecta
What does a missense mutation in either COL1A1 or COL1A2 cause?
Severe osteogenesis imperfecta
What sort of disease is CMT1A (charcot marie tooth) and PMP22 (pulmonary disease)?
Duplication, gain of function, dominant
What sort of disease is Haemophillia A?
Loss of function, X-linked recessive
What type of disease is duchenne muscular dystrophy (DMD)?
loss of function, X-linked recessive
What type of disease are VCFS and WBS?
deltions, loss of function
