Genetic Basis of Human Disease Flashcards
What is a Mendelian disorder?
A disorder that is inherited due to a mutation at a single locus
Example of an autosomal recessive disorder
Alkaptonuria
If both parents are heterozygous carriers of the alkaptonuria mutation, what are the chances of their offspring having alkaptonuria?
25%
What is alkaptonuria?
Defect in the enzyme homogentisate-1,2-dioxygenase (HGD) –> body can’t process tyrosine or phenylalanine
What can’t the body process if you have alkaptonuria?
Tyrosine or phenylalanine
Example of an autosomal co dominant disorder
Sickle cell anaemia
What is an autosome?
Any chromosome that isn’t a sex chromosome
What is sickle cell anaemia caused by?
A single point mutation in amino acid 6 of the ß-globin subunit of haemoglobin…. Glutamate –> Valine
What amino acid is altered in sickle cell anaemia?
Glutamate –> Valine
How can being a heterozygous carrier of sickle cell anaemia help you?
Individuals who are heterozygous carriers exhibit sickle cell trait but exhibit increased resistance to malaria
How is sickle cell anaemia a co dominant disorder?
The alleles exhibit co dominance as the heterozygote sickle cell phenotype is an intermediate between the wild-type and sickle cell
What is karyotyping?
A method which allow distinguishing chromosomes by band patterning and length
What do abnormalities in banding show? (karyotyping)
Shows mutagenic rearrangements have taken place with can then be associated with specific phenotypes
Karyotyping enables…
…genes to be mapped to specific chromosomal locations
Example of autosomal dominant disorders
- Aniridia
- Brachydactyly
- Huntington’s disease
What is anirida?
Absence of an iris
What causes aniridia?
Loss-of-function or deletion mutation in one allele of the gene on chromosome 5
What happens if there are no alleles present in anridia?
It’s embryonic lethal so death
Which gene is associated with aniridia?
PAX6
What is brachydactyly?
Shortened digits
What is Huntington’s disease?
A neurodegenerative disorder in which there is neuronal loss in the basal ganglia and dilation of the lateral ventricles
Which gene is associated with Huntington’s disease?
Huntingtin
What does the mutation in Huntington’s disease cause?
Alters the number of CAG repeats which relates to the disease expression. Expansion of the polyQ tract. Huntingtin toxic to neurons
What is the protein huntingtin associated with?
Synaptic vesicle dynamics and neurotransmitter release
Example of X-linked disorder
- Haemophilia
- Duchenne muscular dystrophy (DMD)
What is DMD?
Duchenne muscular dystrophy, a progressive muscle damage and muscle wasting disease
What is the biggest gene known to humans?
Dystrophin
Which gene is associated with Duchenne muscular dystrophy?
Dystrophin
What genetic difference is there between a patient with DMD and someone without?
Patient with DMD has a region on their X chromosome missing
Where can the DMD gene be located?
Xp21
How was the DMD gene identified?
It was identified by a DNA sequence on the X chromosome that was deleted
What accumulates in joints in alkaptonuria?
Homogentisic acid
