The following diseases are inherited in an X-linked fashion:
b. Retinitis pigmentosa type 3
d. Norrie’s disease
e. Fabry’s disease
Oculocutaneous albinism is inherited in an autosomal recessive fashion. Ocular albinism is inherited in an X-linked fashion. Other X-linked disorders include red-green colour blindness and blue cone monochromacy.
are features of mitochondrial diseases:
Leber’s optic neuropathy is the prototype
“ragged red fibres” may be found on muscle biopsy
There is no transmission from males to their offspring. In Leber’s optic neuropathy, there is an amino acid point mutation in NADH (arginine to histidine). Tissues most reliant on oxygen include the heart, CNS, kidneys, and endocrine organs and these are the most affected by the mitochondrial disease.
Genetic and acquired defects in DNA include:
Transitions, which are commoner than transversions
Deletions which involve relatively large segments of DNA
If a purine changes to another purine the point mutation is called a transition.
If a purine changes to a pyrimidine or vv, the mutation is a transversion.
Transitions outnumber transversions at most human loci.
A nonsense mutation is one that changes a codon that normally specifies an amino acid as a termination.
The polymerase chain reaction:
Depends on the synthesis of DNA by DNA polymerase
In the amplification phase is driven entirely by temperature change
The polymerase chain reaction is a technique that allows small amount of DNA to be amplified for detection and analysis. Synthetic primers are used to trigger the amplification process.
Restriction endonuclease enzymes:
a. Are used in Southern blotting
b. Are used to identify DNA polymorphisms
c. Are used in the polymerase chain reaction
d. Are used for gene mapping
e. With DNA ligase are used to incorporate DNA sequences into plasmids
Restriction endonuclease enzymes cut DNA at specific recognition sites and may be used to identify polymorphisms. In Southern blotting, a DNA sample is cut into several fragments by restriction endonucleases and denatured into single strands. Pre-prepared radiolabeled DNA probes are used to determine any matches with the single-stranded DNA, by identification with autoradiography.
Autosomal dominant conditions include:
a. Stickler’s syndrome
c. Best’s disease
The following diseases are autosomal recessive :
a. Macular corneal dystrophy
b. Hexosaminidase A deficiency
c. Simple myopia
d. Stargardt’s dystrophy
f. familial ectopia lentis
In X-linked recessive conditions:
Usually only males are affected
An affected male transmits the gene to all daughters and none of his sons
Classification of Albinism
OCA1a no pigment and no active tyrosinase
OCA1b some residual tyrosinase activity and so have some pigment
OCA2 affects the p-protein, another protein involved in melanin production
OCA3 is a milder form of albinism caused by the encoding tyrosinase protein 1
OCA4 is clinically indistinguishable from OCA2 - more common in Japan
Genetics of Albinism
mostly autosomal recessive
abnormal gene in 1 / 100 people
both parets must have the recessive gene
ALBINISM IS ASSOCIATED WITH SYSTEMIC CONDITIONS
- Chediak-Higaski syndrome
- Hermansky-pudlak syndrome
- Waardenburg syndrome
Gorlin's syndrome (basal cell naevus syndrome)
- rare, autosomal dominant and multisystem disorder
- characterised by multiple basal cell carcinoma, jaw cysts, skeletal anomalies, ectopic calcification of the falx cerebri and pitting of the hand and feet
- ocular features also include hypertelorism, lateral displacement of the medial canthi and prominent supraorbital ridges
Posterior polymorphous dystrophy:
- a bilateral dominantly inherited dystrophy
- vesicular polymorphous deposits with clear halos in Descemet's membrane
- usually asymptomatic, rarely endothelium decompensation requiring penetrating corneal graft
- the abnormal endothelium may extend into the trabecular meshwork and iris
- glaucoma can occur as a result of trabecular meshwork involvement iris involvement can lead to corectopia and ectopia simulating iridocorneal endothelial syndrome except that the later is unilateral