Download Mutations and Genetic Disease Most genetic diseases are caused

Mutations and Genetic Disease
Most genetic diseases are caused by mutations - differences in the DNA of an individual as
compared to normal human DNA. Sickle cell anemia, a recessive disorder characterized by
chronic anemia, episodic joint pain, and crescent-shaped red blood cells, is a relatively simple
example. Interestingly, it should be noted that carriers of the sickle-cell trait (people that possess
one copy of the recessive gene, as opposed to the two required for full-fledged disease) are
almost exclusively of African descent and seem to have an increased resistance to malaria. Since
malaria is widespread in many parts of Africa, this is a striking example of evolutionary
adaptation in humans.
The sickle cell mutation. One amino acid out of a
total 287 differs in sickle cell haemoglobin
compared with normal haemoglobin. In the latter,
the triplet GAG (guanine, adenine, guanine)
codes for the amino acid glutamic acid (left-hand
diagram). In sickle cell haemoglobin, the
corresponding three-base sequence is GTG
(guanine, thymine, guanine) which codes for the
amino acid valine. This substitution occurs sixth
in line from one of the ends of the beta
haemoglobin chain. [Hemoglobin consists of two
chains of animo acids, the alpha and beta chain.]
This image and caption from The Book of Man
by Walter Bodmer and Robin McKie.
The type of mutation exemplified in sickle cell
anemia is called a substitution, because one nucleotide base is substituted for another. Other
types of mutations include insertions and deletions, both of which can have disastrous
consequences, since they "throw off" the entire sequence of triplet codes from the point of
mutation to the "STOP" code at the end of the gene.
In an insertion mutation, an extra base pair not normally present is added to the code. For
example, a normal DNA sequence of ATTGGCGTA would be translated into triplet codes,
obviously, as ATT GGC GTA. If an insertion mutation was present, causing the code to read
AATTGGCGTA, then the triplet translation would read AAT TGG CGT A.... The end result
would be a change in all amino acids on the protein chain after the mutation. Insertion mutations
often arise as a result of randomly adding genes in gene-therapy tests.
A deletion mutation, in which a base pair is subtracted from the normal code, works much the
same way. To use the same example, if the mutated code read ATGGCGTA, then it would be
translated into triplet code as ATG GCG TA.... The end result is similar to that of an insertion
mutation, with the exception that deletion mutations are more common. Deletions of one or more
base pairs have been associated with certain bowel cancers and with the most common form of
cystic fibrosis, a disease characterized by unusually viscous mucus that impedes normal
respiratory and digestive function.
Chromosomes and Genetic Disease
Some genetic diseases are caused by possession of too many or not enough chromosomes.
Down's Syndrome, a common form of mental retardation, is caused by possession of three
copies of chromosome 21, instead of the usual two. Turner's Syndrome, a condition that causes
infertility and immature sexual development in women, is due to the possession of only one X
chromosome, instead of the two always present in normal women. These types of diseases are
caused by nondisjunction, a failure in the distribution of chromosomes during meiosis.
Other genetic diseases are caused by
chromosome translocation, in which small
parts of chromosomes break and rejoin other
chromosomes. Translocation has been
pinpointed as the cause of chronic myeloid
leukemia, a type of cancer. It may be linked to
other cancers in the future.
Sex-Linked Diseases
With the exception of Turner's Syndrome, all the diseases mentioned so far have been autosomal,
or related to chromosomes 1 - 22 (that is, not related to the sex chromosomes - X and Y). Sexlinked disorders are the opposite - related to the sex chromosomes. These disorders, (also called
X-linked), are recessive, involve the X chromosome, and affect males almost exclusively.
Females are virtually never affected by these disorders because they possess two X
chromosomes, both of which would have to carry the defective gene in order for it to be
manifested. Since these females' fathers would be affected by the disorder, which is usually
debilitating or fatal, this is a highly unlikely situation. (Note that Turner's Syndrome, while
related to the sex chromosomes, is not a true sex-linked disorder.)
Examples of sex-linked disorders include Duchenne muscular dystrophy, a progressive
degeneration of muscle tissue; fragile-X syndrome, a common form of mental retardation in
boys; and hemophilia, a disease in which a deficiency in one of several blood-clotting factors
causes uncontrollable bleeding. This disease was made famous by Queen Victoria of England,
who was a carrier of the disease and spread it throughout the European royal lines. Part of her
family pedigree is shown below. The Empress Alexandra of Russia (not shown), a descendant of
Victoria and a carrier of the disease, married the last Czar of Russia, Nicholas Romanov. The
couple had four daughters and a son, Alexei, who was affected by hemophilia. The couple
allowed the Siberian mystic Rasputin to enter their court because he seemed to control their son's
bouts of bleeding, but Rasputin's political influence and personal habits contributed to the Czar's
downfall during the Russian Revolution of 1917.
Dominant Genetic Diseases
Without exception, all the diseases mentioned so far have been recessive. Dominant inherited
diseases are very rare, because victims of these diseases tend to die before reproducing, and thus
passing on the gene for the disease. As a result, the few dominant inherited diseases that do exist
rarely manifest themselves before late middle age. One example, called Huntington's chorea,
has been described as "the most demonic of diseases". Its symptoms include depression,
dementia, exhaustion, extreme weight loss, and constant jerking movements of the limbs - the
hallmark of the disease. Because it is a dominant disorder, a child of a Huntington's victim has a
50% chance of also succumbing to it. This simple pattern of inheritance has allowed scientists to
study the disease in detail.
Ethnic Heritage and Genetic Disease
Certain genetic diseases are often associated with specific ethnic groups. Sickle cell anemia, as
discussed above, is almost exclusively present in people of African descent. Tay-Sachs disease,
a fatal disorder that causes blindness and mental retardation, is most prevalent in people of
Jewish descent. The highest concentrations of Tay-Sachs victims are among Jews of German or
East European origin. (This has been linked to the high incidence of tuberculosis in these
regions.) Cystic fibrosis, also mentioned above, most often affects people of Caucasian ethnicity.
As discussed before in the example of sickle cell anemia, the concentration of victims in people
from a particular area can reflect human evolutionary adaptation.
In summary, genetic diseases are diverse and varied. They have very different genetic causes and
origins, and they affect different ethnic populations. In addition, some genetic diseases are
caused by multiple defective genes inherited together, or by different genes in different victims.
Often, disease-causing genes are spread out over a large part of a chromosome, or even over
different chromosomes. Also inheritable are genetic predispositions to other diseases such as
cancer, AIDS, heart disease, high cholesterol, and high blood pressure. All these facts make it
difficult for genetic researchers to track the genes that cause these diseases. However, with the
help of the Human Genome Project and new technology being developed, the genes will finally
be identified, and help will be available for the tragic victims of genetic diseases.
Human Mutations are seen as birth defects that a person has to live throughout their life with.
Some are very visible to the eye while others can be hidden.
Cyclopia
This birth defect doesn’t allow the orbits of the eyes to separate into two cavities. These
occurrences happen in every 1 in 250 babies. The face will be missing or the nose will be nonfunctioning and that nose will either be above the eye or on the back of the head. Most babies
will not make it to birth or they are still born. There are two cases of children with Down
Syndrome that have been born with one eye. This is often caused by genetic problems or toxins
ingested by the mother.
Tree Man
This man has hands and feet that look like contorted tree branches. For 20 years, he has lived like
this. He has warts all over his body that look like the moss that forms on trees out in the forest.
The growths on his body make up over twelve pounds of his weight and he only weighs 100
pounds. After only a few steps he would become tired because of the density of the growths. It is
believed that this defect was caused by an HPV virus. There are two types of HPV. The first one
can cause cervical cancer and the other can cause warts on the skin. This is what the doctor’s feel
he has. The warts started to appear after he received a cut on his skin as a teenager. It has become
out of control since then. The skin has infections happening and bugs living in his skin. He has a
weak immune system and the virus took over because of it.
Mermaid Syndrome
This is when a child is born with his or her legs fused together and it gives the impression of a
mermaid’s tail. One out of every 100,000 births are said to have this birth defect. The babies
born with this defect will die within a day or two because of complications in the development of
their bladders and kidneys. There are only a handful of births that did not have the complications
that came along with this condition. Three of the most well know cases are Milagros Cerron,
Tiffany Yorks and Shiloh Pepin.
Werewolf Syndrome
This birth defect or genetic mutation has to do with the hair on the person’s body growing to a
substantial amount over every inch. This can be seen at birth, when the child is born covered in
hair. If the infant is tested and does not suffer from hypertrichosis, then the hair will be shed over
the next few years. The acquired type of gene forms over the years and can refer to extra hair
growing in places that hair hasn’t grown before..
Gigantism
Gigantism is when a person grows to an excessive height above the normal average adult. There
are two types of gigantism. One is called pituitary gigantism, which causes the person to grown
excessively in height and weight. Then there is a cerebral gigantism, which causes the brain to
grow in an excessive amount causing mental retardation. In order to be diagnosed with this
disease you have to be above one percent on several variations that are unhealthy for your
genetic make up.
Dwarfism
Dwarfism is used to describe a person that is less than 4 feet 10 inches tall, depending on the
area. Some places have adults that are this tall and shorter for that area. There are over 200
causes of dwarfism. There is no cure for dwarfism. It can be caused by one or more genetic
disorders. With dwarfism, comes negativity in society. There are those people that believe a
dwarf has less intelligence or a social behavioral problem, but this is untrue. They can live and
lead a normal live, with the same life span as an average person.
Elephantiasis
This mutation will make the skin and underlying tissue swell and thicken. It is most commonly
seen in the legs, scrotum or breasts. This is generally caused by a parasite released into the blood
stream by a mosquito bite. The severity depends on the person’s immune system and the ability
to fight the disease. It is commonly found in Africa. There are treatments for this mutative
disease and some are effective. There is possible talk of eliminating the disease within the next
eleven years.
Arnold Syndrome
This syndrome has to do with missing clavicle bones. Everyone with this mutation is the
descendant of one man. They are able to move their shoulders forward to the point of almost
touching. Arnold had this mutation and took on seven wives and they all had children and the
mutation was passed on. It has continued to be passed on throughout the years and all the people
that have this mutation seem to know that the other person has it and realized that they are
relatives in some way.
Link
The discovery of these mutations is some of the wonders of science. Some baffled the scientific
world for years and most of the people that had these genetic mutations were outcasts. They were
sent away from their villages, towns or cities and they ended up performing in circuses as the
sideshow freaks. They may have been able to make a living and were accepted that way, but they
were still the outcasts that no one wanted to deal with except on the circus level.