Genetics: Single gene disorders

Question 1

Gene therapy - why have results been disappointing?

Answer 1

Immune response to vector (viruses/liposomes) and inflammatory responses

Question 2

Haemophilia A - mode of inheritance.

Answer 2

X-linked Recessive

Question 3

X-linked severe combined immune deficiency disorder - mode of inheritance.

Answer 3

X-linked Recessive

Question 4

Congenital deafness - mode of inheritance.

Answer 4

X-linked Recessive

Question 5

Retinitis pigmentosa - mode of inheritance.

Answer 5

X-linked Dominant

Question 6

Chondroplasia punctata - mode of inheritance.

Answer 6

X-linked Dominant

Question 7

Hypophosphataemic rickets - mode of inheritance.

Answer 7

X-linked Dominant

Question 8

Cystic fibrosis - mode of inheritance.
How common is CF?
What is the mutation?

Answer 8

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.

Question 9

Tay-Sachs - mode of inheritance.

Answer 9

Autosomal recessive

Question 10

Haemachromatosis - mode of inheritance.

Answer 10

Autosomal recessive

Question 11

Phenylketonuria - mode of inheritance.

Answer 11

Autosomal recessive

Question 12

Huntingtons disease - mode of inheritance.

What is the molecular change?

Answer 12

Autosomal dominant.

Chromosome 4 - molecular mutation. GCC, CAG and other repeat expansion –> polyglutamine Inclusions

Question 13

Achondroplasia - mode of inheritance.

Answer 13

Autosomal dominant.

Question 14

Polycystic kidney disease - mode of inheritance.

Answer 14

Autosomal dominant. Chromosome 4.

Question 15

Fragile X mental retardation - what is the molecular change?

Answer 15

Molecular transcription control issue - GCC,CAG

and other repeat expansion.

Question 16

Alzheimer’s disease - what are the molecular changes? What genes?

Answer 16

Mutation - alternative splicing, mis-sense, non-sense, frame-shift
RNA editing
Aneuploidy

Presenilin 1,2 and APP and ApoE4 allele

Question 17

Alzheimer’s disease - what are the molecular changes? What genes?

Answer 17

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

Question 18

Down’s syndrome - what is the molecular change?

Answer 18

Aneuploidy (chr 21)

Question 19

Reigar syndrome

Answer 19

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

Question 20

Pre-axial polydactyly

Answer 20

Switch from G to A

Question 21

What gene therapy is effective?

Answer 21

Severe combined immunodeficiencies (X-SCID) -
initial success but leukaemia in two patients.
Sibling bone marrow transplantation (BMT) also effective.

Question 22

What gene therapy is effective?

Answer 22

X-SCID initial success but leukaemia in two patients.

Sibling bone marrow transplantation (BMT) also effective.

Question 23

What conditions are more suitable for gene therapy?

Answer 23

Recessive
Loss of function mutation
Tissue accessible eg. skin, blood
Small gene