GENETIC DISORDERS
1. Chromosome Disorders
A. Down Syndrome
Down syndrome is also called trisomy 21 because the person’s chromosome number 21
has three chromosomes joined together instead of just two. The chances of a woman
having a Down syndrome child increase rapidly with age, starting at about age 40.
The frequency of Down syndrome is 1/ 800 births for mothers under 40 years of age, but
women over 40 are 10 times more likely to have a Down syndrome child.
Characteristics of Down syndrome include a short stature; an eyelid fold; stubby
fingers; a wide gap between the first and second toes; a large, fissured tongue; a round
head; a palm crease (the so-called simian line), and mental retardation, which can
sometimes be severe. Their personalities are usually cheerful, good-natured, and pleasant
throughout their lives.
Amniocentesis (removing fluid and cells from the amniotic sac surrounding the fetus)
followed by karyotyping can detect a Down syndrome child.
Scientists have located genes most likely responsible for the increased tendency toward
leukemia, cataracts, accelerated rate of aging, and mental retardation. One day it might be
possible to control the expression of that gene even before birth so that at least this
symptom of Down syndrome does not appear.
B. Cri du Chat Syndrome (“cat’s cry”)
This is caused by one missing chromosome 5 and occurs in 1/ 50,000 live births. An
infant with this syndrome has a moon face, small head, and a cry that sounds like the
meow of a cat because of a malformed larynx. An older child has an eyelid fold and
misshapen ears that are placed low on the head. Severe mental retardation becomes
evident as the child matures.
2. Sex Chromosomal Disorders
All of the cells in our body have all of our chromosomes in the nucleus except for the egg
and the sperm. Each of these has all of our chromosomes in the nucleus, except there is
only one of the two sex chromosomes. Since women are XX, all of her egg cells are X,
but since males are XY, a sperm can bear an X or a Y. Therefore, the sex of the
newborn child is determined by the father. If a Y. bearing sperm fertilizes the egg,
then the XY combination results in a male. On the other hand, if an X-bearing sperm
fertilizes the egg, the XX combination results in a female.
All factors being equal, there is a 50% chance of having a girl or a boy. If a couple has 10
children and they are all boys, what is the chance that an eleventh child is going to be a
boy? Interestingly, the death rate among males is higher than for females. By age 85,
there are twice as many females as males.
A. Jacob syndrome occurs in 1/ 1,000 births. These XYY (an extra male
chromosome) males are usually taller than average, suffer from persistent acne, and
tend to have speech and reading problems. At one time, it was suggested that these
men were likely to be criminally aggressive, but it has since been shown that the incidence of such behavior among them may be no greater than among XY males.
B. Klinefelter syndrome occurs in 1/ 1,500 births. These males with XXY (an extra
female chromosome) and they are sterile. They are males with some female
characteristics. The testes are underdeveloped, they have some breast development, and
there is no facial hair. They are usually slow to learn but not mentally retarded.
C. Triple-X syndrome occurs in 1/ 1,500 births. These are females with an extra
female chromosome: XXX. You might think they are especially feminine, but this is not
the case. Although in some cases there is a tendency toward learning disabilities, most
have no physical abnormalities except that they may have learning disabilities,
menstrual irregularities, including early onset of menopause.
D. Turner syndrome occurs in 1/ 6,000 births. The individual is XO, meaning one
of the sex chromosomes is missing. These are females and have a short, have a broad
chest, and webbed neck. The ovaries and uterus are nonfunctional. Turner females do not
undergo puberty or menstruate, and there is a lack of breast development. They are
usually of normal intelligence and can lead fairly normal lives, but they are infertile even
if they receive hormone supplements.
3. Dominant Disorders (only one dominate allele needs to be present)
A. Neurofibromatosis
Also known as Elephant Man disease, this is one of the most common genetic disorders.
It affects roughly 1/ 3,000 people. It is seen equally in every racial and ethnic group
throughout the world. At birth or later, the affected individual may have six or more
“coffee with milk” colored spots (known as cafe-au-lait) on the skin. Such spots may
increase in size and number and may get darker. Small benign tumors (lumps) called
neurofibromas may occur under the skin or in various organs.
In most cases, symptoms are mild, and patients live a normal life. In some cases,
however, the effects are severe. Skeletal deformities, including a large head, are seen, and
eye and ear tumors can lead to blindness and hearing loss. Many children with
neurofibromatosis have learning disabilities and are hyperactive. The abnormal gene is on
chromosome 17.
B. Huntington Disease
This affects 1/ 20,000 people. It is a dominant neurological disorder that leads to
progressive degeneration of brain cells, which causes severe muscle spasms and
personality disorders. Most people appear normal until they are of middle age and have
already had children who might also be stricken. There is no effective treatment, and
death comes ten to fifteen years after the onset of symptoms.
4. Homozygous Recessive Disorders (both parents must have rr alleles)
A. Tay - Sachs disease
This disease usually occurs among Jewish people. At first, it is not apparent that a baby
has Tay-Sachs disease. However, development begins to slow down between four months
and eight months of age, and neurological impairment and psychomotor difficulties then
become apparent. The child gradually becomes blind and helpless, develops
uncontrollable seizures, and eventually becomes paralyzed. There is no treatment or
cure for Tay-Sachs disease, and most affected individuals die by the age of three or four.
It is caused by a genetic enzyme deficiency.
B. Cystic Fibrosis
This is the most common lethal genetic disease among Caucasians in the United
States. About 1 in 20 Caucasians is a carrier, and about 1/ 2,500 births have the disorder.
In these children, the mucus in the bronchial tubes is particularly thick and interferes
with breathing, and the lungs get infected frequently.
New treatments have raised the average life expectancy to 28 years of age. The cystic
fibrosis gene is located on chromosome 7.
C. Phenylketonuria (PKU)
This occurs in 1 / 5,000 births, so it is not as frequent as the disorders previously
discussed, however, PKU is tested for in routine blood screenings of all newborns in the
United States. This is the disease that offspring of first cousins are more likely to get.
PKU people lack an enzyme that is needed to break down an amino acid
(phenylalanine), and so the amino acid accumulates in the urine. These people have to
have a special diet that does not contain that amino acid. If they get too much of it, they
will get neurological problems and mental retardation. That’s why nutrition labels have to
warn when they contain phenylalanine.
5. Incompletely Dominant Traits
Incomplete dominance is exhibited when there is an intermediate phenotype. These
people can be carriers of a disorder without being sick themselves. Their children may
have the disorder, or they also may be carriers. When they are carriers, they are said to
have the “trait” of the disorder, but not the disease.
A. Sickle-Cell Disease
This is an incompletely dominant disorder. In persons with sickle-cell disease, the red
blood cells aren’t round disks like normal red blood cells; they are irregular. In fact,
many are sickle shaped, like a banana with points on both ends. The red blood cells do
not carry oxygen well, and they get stuck in arteries also.
Therefore, they suffer from poor circulation, anemia, poor resistance to infection, internal
bleeding, pain in the abdomen and joints, and damage to internal organs.
In malaria-infested Africa, infants with sickle-cell disease die (they got a bad
chromosome from both parents), but infants with sickle-cell trait (they got a bad
chromosome from only one parent) actually have better resistance to malaria than a
normal human being. The malaria parasite normally reproduces inside red blood cells.
But a red blood cell of a sickle-cell trait infant kills the parasite.
Therefore, the only people who survive in Africa well are those with sickle cell trait.
That’s why about 60% of the population in malaria-infested regions of Africa has sickle
cell trait. Unfortunately, 25% of their offspring can get the sickle cell disease.
6. Sex-Linked Traits
Traits controlled by alleles on the sex chromosomes are said to be sex-linked; an allele
that is only on the X chromosome is X-linked, and an allele that is only on the Y chromosome is Y-linked. Most sex-linked alleles are on the X chromosome since it is larger.
A. X-Linked Disorders
X-linked conditions can be dominant or recessive, but most known are recessive.
More males than females have the trait.
If a male has an X-linked condition, his daughters are often carriers, so her male children
are also likely to have the condition.
Male Pattern baldness is from a gene that is inherited from the mother. For you guys, if
your mother’s father was bald, you are more likely to be bald. It doesn’t matter if your
father is bald or if his father is bald. You get the baldness gene from your mother’s father.
Three well-known X-linked recessive disorders (more common in males than females)
are color blindness, muscular dystrophy, and hemophilia.
1) Color Blindness
In the human eye, there are three different types of cone cells (remember, they sense
color vision). These different types are sensitive to either the color red, green, or blue.
The gene for the red and green cells is on the X chromosome.
COLOR BLINDNESS TEST
About 8% of Caucasian men have red-green color blindness. Opticians have special
charts by which they detect those who are color blind.
2) Muscular Dystrophy
As you can tell by the name, this disease is characterized by a wasting away of the
muscles. The most common form is X-linked and occurs in about 1/ 3,600 male births.
Symptoms, such as waddling gait, toe walking, frequent falls, and difficulty in rising,
may appear as soon as the child starts to walk. Muscle weakness progresses to the point
where they need a wheelchair. Death usually occurs by age 20; therefore, affected males
are rarely fathers. The disease is from a carrier mother to carrier daughter.
3) Hemophilia
About 1/10,000 males is a hemophiliac. It is due to the absence of a clotting factor. It is
called the bleeder’s disease because the blood does not clot. Every time they get a bruise,
they have to have either a blood transfusion or an injection of a clotting protein, which
they keep in their refrigerator since they need it so often.
In the early 1900’s, hemophilia was prevalent among the royal families of Europe, and all
of the affected males could trace their ancestry to Queen Victoria of England. Of her 26
grandchildren, five grandsons had hemophilia and four granddaughters were carriers.
Because none of Queen Victoria’s forebears or relatives were affected, it seems that the
faulty allele she carried arose by mutation either in Victoria or in one of her parents. Her
carrier daughters, Alice and Beatrice, introduced the gene into the ruling houses of Russia
and Spain, respectively. Alexis, the last heir to the Russian throne before the Russian
Revolution, was a hemophiliac. There are no hemophiliacs in the present British royal
family because Victoria’s eldest son, King Edward VII, did not receive the gene and
therefore could not pass it on to any of his descendants.
7. Sex-Influenced Traits
The length of the index finger is sex-influenced. In females, an index finger longer than
the fourth finger (ring finger) is dominant. In males, an index finger longer than the
fourth finger seems to be recessive.