GENETIC MUTATIONS
Genetic mutations are alterations in the DNA of chromosomes. It is a permanent
change in the DNA sequence of a gene. Mutations in a gene's DNA sequence can alter the
amino acid sequence of the protein encoded by the gene. How does this happen? Like
words in a sentence, the DNA sequence of each gene determines the amino acid sequence
for the protein it encodes. The DNA sequence is interpreted in groups of three
nucleotide bases, called codons. Each codon specifies a single amino acid in a protein.
We can think about the DNA sequence of a gene as a sentence made up entirely of
three-letter words. In the sequence, each three-letter word is a codon, specifying a
single amino acid in a protein. Have a look at this sentence:
Thesunwashotbuttheoldmandidnotgethishat.
If you were to split this sentence into individual three-letter words, you would probably
read it like this:
The sun was hot but the old man did not get his hat.
This sentence represents a gene. Each letter corresponds to a nucleotide base, and each
word represents a codon.
There are two types of mutations:
frameshift and point.
FRAMESHIFT:
What if you shifted the three-letter "reading frame?" You would end up
with
hes unw ash otb utt heo ldm and idn otg eth ish at.
Or
TTh esu nwa sho tbu tth eol dma ndi dno tge thi sha t.
Insertion mutations and deletion mutations add or remove one or more
DNA bases. Insertion and deletion mutations cause frameshift mutations,
which change the grouping of nucleotide bases into codons. This results in
a shift of "reading frame" during protein translation. The proteins are
completely nonfunctional.
POINT MUTATIONS:
Point mutations are single nucleotide base changes in a gene's DNA
sequence. This type of mutation can change the gene's protein product in
the following ways:
 Missense mutations are point mutations that result in a single amino acid change within
the protein.
UAC – CAC – this leads to a change in shape of protein and its function.
The fat cat. – The fat rat.
 Nonsense mutations are point mutations that create a premature "translation stop
signal" (or "stop" codon), causing the protein to be shortened.
UAC – UAG.
The fat
cat. – the fat.
 Silent mutations are point mutations that do not cause amino acid changes within the
protein (they have no observable effect on an organism). A silent mutation changes a
nucleotide without changing the codon. For many amino acids the third nucleotide of the
codon can be variable. For example, CCT, CCC, CCA and CCG all code for Proline. The fat
cat.
- The fat cat.
Mutations can occur randomly and spontaneously (errors in replication), or they
can be induced (mutagens, which are environmental factors that effect DNA like
radiation, UV light, viruses, diet, alcohol).
DNA damage from environmental agents
Modifying nucleotide bases
Ultraviolet light, nuclear radiation, and certain chemicals can damage DNA by altering
nucleotide bases so that they look like other nucleotide bases.
When the DNA strands are separated and copied, the altered base will pair with an
incorrect base and cause a mutation. In the example below a "modified" G now pairs with
T, instead of forming a normal pair with C.
Mistakes created during DNA duplication
Prior to cell division, each cell must
duplicate its entire DNA sequence. This
process is called DNA replication.
DNA replication begins when a protein
called DNA helicase separates the DNA
molecule into two strands.
Next, a protein called DNA polymerase copies each
strand of DNA to create two double-stranded
DNA molecules.
Mutations result when the DNA polymerase makes a
mistake, which happens about once every 100,000,000 bases.
The number of mistakes that remain incorporated into the DNA is even lower than this
because cells contain special DNA repair proteins that fix many of the mistakes in the
DNA that are caused by mutagens. The repair proteins see which nucleotides are paired
incorrectly, and then change the wrong base to the right one.
We can separate genetic disorders into four categories:
1. Chromosome Abnormalities
2. Single-Gene Disorders
In some disorders, entire chromosomes, or large
Some disorders result when a mutation causes the
segments of them, are missing, duplicated, or
protein product of a single gene to be altered or
otherwise altered. Down Syndrome and Turner's
missing. An example of this kind of disorder is sickle
Syndrome are examples of this type of disorder.
cell anemia.
3. Multifactorial Disorders
4. Mitochondrial Disorders
Multifactorial disorders result from mutations in
These relatively rare disorders are caused by
multiple genes, often coupled with environmental
mutations in non-chromosomal DNA located within
causes. The complicated bases of these diseases
subcellular organelles, the mitochondria. There are
make them difficult to study and to treat. Heart
multiple copies in a single cell's cytoplasm, all
disorder, diabetes and cancer are examples of this
transmitted by the mother in the ovum.
type of disorder.