Biology Reference
In-Depth Information
(mtDNA). A process called oxidative phosphorylation (OXPHOS) takes
place in the mitochondria and is responsible for energy (ATP) production
in the cell. Each mitochondrion has multiple copies of mtDNA and each
cell contains several hundred mitochondria, and thus many copies of
mtDNA. The mutation rate is ten times higher in mtDNA than in nuclear
DNA, and cells may contain both mutant copies and normal copies, a con-
dition known as heteroplasmy. If the normal copies can successfully provide
the energy requirements of the cell, then normal function will be retained.
However, different cell types have differing energy requirements. The
organs with the most demand for energy are the skeletal muscle, heart, eye,
ear, and brain. Thus, the typical symptoms found in mitochondrial disorders
are muscle weakness, nervous system disorders, visual problems, hearing
loss, and dementia.
The mtDNA molecule is circular and consists of about 16,000 base pairs.
Mitochondria are maternally inherited, so the expected family history for
a mitochondrial disorder is that all children of an affected mother are
affected, and children of an affected father are never affected. However,
because of heteroplasmy, the mother and siblings of an affected individ-
ual may show only minor symptoms, or none at all. Mitochondrial
disorders that involve hearing loss are discussed by Fischel-Ghodsian
(Chapter 7).
2. The Genetic Material
Each chromosome consists of a single molecule of deoxyribonucleic acid
(DNA), which has a double-helical structure. DNA is composed of a sugar-
phosphate backbone and four bases: adenine (A) and guanine (G) are
purines, and thymine (T) and cytosine (C) are pyrimidines. The double helix
is formed through the pairing of A with T, and C with G, and the bases are
held together by hydrogen bonds. Thus, knowing the sequence of bases on
one DNA strand automatically gives the sequence on the other strand. This
precise pairing means that DNA can replicate by separation of the two
strands, followed by each strand serving as a template for a new comple-
mentary strand.
The set of 24 chromosomes has three billion base pairs, of which 1% to
2% make up the estimated 35,000 human genes. Genes consist of both
coding sequences (exons) and intervening sequences (introns), and it is
the exons that encode the amino acid sequence of the protein product. The
connecting link between the gene (DNA) and the protein is messenger
ribonucleic acid (mRNA). The sequence of bases in the exons is called
the complementary DNA (cDNA) sequence because it can be synthesized
using the mRNA as a template. The three major differences between DNA
and RNA are: (1) DNA is double-stranded, RNA is single-stranded; (2) the
