Page 213 - Concise Pathology for Exam Preparation ( PDFDrive )

198 SECTION I General Pathology

Q. What is multifactorial inheritance?
Ans. Multifactorial (polygenic) inheritance disorders occur consequent to multiple small
mutations plus the effect of environment.
Examples: Cleft lip or palate, congenital heart disease, coronary artery disease, gout,
type II diabetes mellitus, hypertension, open neural tube defects and congenital pyloric
stenosis.

Q. What are mitochondrial DNA disorders?

Ans. Mitochondrial DNA (mtDNA) disorders arise secondary to mutations in a
mitochondrial genes, which primarily code for enzymes involved in oxidative
phosphorylation.
• The disorders are unique to females (mitochondrial genes are inherited by maternal in-
heritance, since ova have more mitochondria than sperms which lose their mitochondria
during fertilization).
• A female with an mtDNA defect transmits it to all her children.
• mtDNA in humans has 37 genes, of which 22 are transcribed into transfer RNAs and
2 into ribosomal RNAs. The remaining code for enzymes of oxidative phosphorylation
pathway.
• Mitochondrial disorders, therefore, affect organs like CNS, skeletal and cardiac muscle,
liver and kidney which are dependent on oxidative phosphorylation.
• Leber hereditary optic neuropathy, a neurodegenerative disease, is a prototype of
mitochondrial disorders. It manifests with bilateral loss of central vision, cardiac
conduction defects and neurological aberrations.

Q. Write briefly on the various molecular techniques used in
pathology.
Ans. Hybridization is defined as the process of double-stranded molecule formation that
occurs between target DNA or RNA and their complementary nucleic acid probes.

Probes
Segments of DNA or RNA labelled with radioisotope or nonradioisotope reporter
molecules, which may be
1. Short single-stranded oligonucleotides.
2. Intermediate-sized complementary RNA probes.
3. Long double-stranded DNA probes.
• Hybridization can be accomplished in solution (polymerase chain reaction or PCR), on
solid support such as nitrocellulose or nylon membranes (Southern blot), or at the cellular or
subcellular level (in situ hybridization).
• Factors that affect the formation and stability of hybridization are composition of
sequences and temperature and salt concentration. Higher temperature and low salt
level lead to stringent hybridization, whereas low temperature and high salt concen-
tration lead to relaxed hybridization with occasional mismatched base pair. Guanine
cytosine (GC)-rich sequence forms a more stable product than an adenine cytosine
(AC)-rich sequence because the former contains more hydrogen bonds that require
a higher temperature to dissociate the hybrid structure. A direct relationship exists
between DNA stability and its melting temperature.

Southern Blotting
In this filter hybridization method, denatured DNA is immobilized on an inert support
that allows for the binding of a labelled nucleic acid probe.

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