The document discusses mitochondrial inheritance, detailing the structure and function of mitochondrial DNA, which comprises 37 genes important for oxidative phosphorylation. It explains maternal transmission of mitochondrial traits and the concept of heteroplasmy, where mutations can lead to varying distributions of mitochondrial DNA in daughter cells. Additionally, it describes mitochondrial disorders such as MELAS and MERRF, highlighting their symptoms, genetic underpinnings, and impact on high-energy tissues.

1. MITOCHONDRIAL
INHERITNCE
HARSHITA SHARMA
190014155003
MSc. Biotechnology
IVth Semester

2. THE MITOCHONDRIAL GENOME:
• Apart from the nucleus DNA is also found within another cellular organelle,
the mitochondrion.
• Each mitochondrion contains multiple copies of a double-stranded, circular
DNA molecule of 16,569 base pairs.
• This DNA has 37 genes out of which encodes 13 peptides that are subunits
of proteins required for oxidative phosphorylation.
• There is a complete set of 22 transfer RNAs and two ribosomal RNAs.

3. The structure of the
mitochondrial genome bears
more resemblance to
prokaryotic than to eukaryotic
genomes. The genes lack
introns and are transcribed as
polycistronic messages from
two promoters. The spaces
between genes consist of
tRNAs, whose excision from
the polycistronic message
releases the individual gene
transcripts. There are also two
sites for initiation of DNA
synthesis, one on each strand
of the double helix.

4. PATTERN OF INHERITANCE:
• A number of clinical disorders have been identified that are due to
mutations within mitochondrial genes. As might be expected, these
traits are associated with failure of mitochondrial energy production.
• Mitochondrial DNA exhibits two critical differences from the nuclear
genome that account for unusual patterns of inheritance of
mitochondrial genetic traits.
• These are:
MATERNAL
TRANSMISSION
HETEROPLASMY

5. MATERNAL GENETIC TRANSMISSION:
• The trait is transmitted from a mother to
all of her children, but is not transmitted
by males.
• This is due to the fact that essentially all
of the mitochondria are maternally
inherited.
• At the time of fertilization only, the
sperm nucleus enters the egg.
Mitochondria in the sperm are shed prior
to fertilization. There may be minor
exceptions to this rule but, for the most
part, mitochondrial traits are maternally
inherited.

6. Maternal genetic transmission. An affected woman transmits the
trait to all of her children. Affected men do not pass the trait to
any of their offspring.

7. HETEROPLASMY: • Unlike the nuclear genome,
which is represented by one
complete copy per cell, there
are hundreds of
mitochondrial DNA
molecules in each cell. These
mitochondria separate
passively when a cell divides,
in contrast to the orderly
separation of chromosomes
in the nuclear genome
during cell division. If some
of the mitochondria contain
a mutation and others do
not, the result can be
unequal distribution of
mutant and nonmutant
mitochondria to daughter
cells.

8. MITOCHONDRIAL DISORDERS:
• Mitochondrial diseases can arise through mutation in mitochondrial DNA
or mutation in nuclear DNA which encodes mitochondrial protein.
• Mitochondria are responsible for the generation of adenosine
triphosphate (ATP) via aerobic metabolism and tissues which consume
high energy such as brain tissues, heart, skeletal muscles can be severely
affected.
• Mitochondrial genetic disorders caused by mutations in nuclear DNA
may follow an autosomal dominant, autosomal recessive, or X-linked
pattern of inheritance.

10. SYNDROMES:

11. MELAS:
• MELAS (MIM 540000) is an acronym for
mitochondrial encephalomyopathy, lactic acidosis,
and stroke-like episodes. The disorder may
present at any time in life with progressive
neurological deterioration and seizures. There are
events in which there is sudden onset of
neurological deficit that have the time course of
strokes.
• Lactic acid tends to accumulate in the blood,
especially during stroke-like episodes. Lactic acid
is a byproduct of the failure of aerobic
metabolism in the mitochondria.
• Various mitochondrial mutations can be
responsible for MELAS. The most common is a
mutation in the mitochondrial gene for leucine
tRNA (MIM 590050).

12. MERRF:
• Myoclonic epilepsy with ragged red fibers
(MERRF) is a multisystem disorder
characterized by myoclonus, which is often the
first symptom, followed by generalized
epilepsy, ataxia, weakness, and dementia.
• Symptoms usually first appear in childhood or
adolescence after normal early development.
The features of MERRF vary widely from
individual to individual, even within families.
• Other common findings include hearing loss,
short stature, optic atrophy, and
cardiomyopathy with Wolff-Parkinson-White
(WPW) syndrome.
clumps of diseased mitochondria accumulate in the
subsarcolemmal region of the muscle fiber and
appear as "Ragged Red Fibers" when muscle is
stained with modified Gömöri trichrome stain

14. REFERENCES:
• Hartwell and Goldberg, From genes to genomes/Patterns of inheritance
• https://rarediseases.info.nih.gov/
• www.ncbi.nlm.nih.gov

15. THANK YOU