Genetics: Single gene disorders Flashcards
(23 cards)
Gene therapy - why have results been disappointing?
Immune response to vector (viruses/liposomes) and inflammatory responses
Haemophilia A - mode of inheritance.
X-linked Recessive
X-linked severe combined immune deficiency disorder - mode of inheritance.
X-linked Recessive
Congenital deafness - mode of inheritance.
X-linked Recessive
Retinitis pigmentosa - mode of inheritance.
X-linked Dominant
Chondroplasia punctata - mode of inheritance.
X-linked Dominant
Hypophosphataemic rickets - mode of inheritance.
X-linked Dominant
Cystic fibrosis - mode of inheritance.
How common is CF?
What is the mutation?
Autosomal recessive
Most common autosomal recessive disease in populations of northwestern European origin - one in 20 carries a defective CF gene. 1 in 1600 births has CF.
Most = 3-bp deletion that results in the loss of phenylalanine.
Tay-Sachs - mode of inheritance.
Autosomal recessive
Haemachromatosis - mode of inheritance.
Autosomal recessive
Phenylketonuria - mode of inheritance.
Autosomal recessive
Huntingtons disease - mode of inheritance.
What is the molecular change?
Autosomal dominant.
Chromosome 4 - molecular mutation. GCC, CAG and other repeat expansion –> polyglutamine Inclusions
Achondroplasia - mode of inheritance.
Autosomal dominant.
Polycystic kidney disease - mode of inheritance.
Autosomal dominant. Chromosome 4.
Fragile X mental retardation - what is the molecular change?
Molecular transcription control issue - GCC,CAG
and other repeat expansion.
Alzheimer’s disease - what are the molecular changes? What genes?
Mutation - alternative splicing, mis-sense, non-sense, frame-shift
RNA editing
Aneuploidy
Presenilin 1,2 and APP and ApoE4 allele
Alzheimer’s disease - what are the molecular changes? What genes?
Mutation - alternative splicing, mis-sense, non-sense, frame-shift
RNA editing of beta amyloid precursor protein
Aneuploidy
Presenilin 1,2 and APP and ApoE4 allele
Down’s syndrome - what is the molecular change?
Aneuploidy (chr 21)
Reigar syndrome
Caused by transcription control issues
–> Epigenetics, positional neighbourhood effects, and mutation of regulatory elements
CHROMOSOME 4
–> craniofacial abnormalities, underdeveloped teeth, eye abnormalities e.g. glaucoma
Pre-axial polydactyly
Switch from G to A
What gene therapy is effective?
Severe combined immunodeficiencies (X-SCID) -
initial success but leukaemia in two patients.
Sibling bone marrow transplantation (BMT) also effective.
What gene therapy is effective?
X-SCID initial success but leukaemia in two patients.
Sibling bone marrow transplantation (BMT) also effective.
What conditions are more suitable for gene therapy?
Recessive
Loss of function mutation
Tissue accessible eg. skin, blood
Small gene
