Genetic Diseases
and Disorders
A genetic disease is caused by the abnormal
expression of one of more genes. These conditions
can be caused by a number of possible pathways:
genetic mutation, abnormal chromosome number,
incorrect gene sequencing, and defective genes.
Currently there are about 4,000 known genetic
disorders, with new ones discovered every year. The
vast majorities of the disorders are quite rare, and
affect only one out of several thousand or million
people.
Disorders caused by gene mutations
These disorders result when a mutation
causes the protein product of a single
gene to be altered or missing.
Cystic Fibrosis
Cystic fibrosis is the most common genetic disorder, with
approximately 5 percent of the U.S. population carrying a copy
of the defective gene.
Cystic fibrosis (CF) is caused by a defective gene which causes
the body to produce abnormally thick and sticky fluid, called
mucus. This mucus builds up in the breathing passages of the
lungs and in the pancreas, the organ that helps to break down
and absorb food. This collection of sticky mucus results in lifethreatening lung infections and serious digestion problems.
Millions of Americans carry the defective CF gene, but do not
have any symptoms. That's because a person with CF must
inherit two defective CF genes -- one from each parent.
Main problems with CF:
•Thick mucus builds up in
the lungs allowing for the
growth of bacteria that can
cause severe infections.
•In addition, with CF, there is
a deficiency of a digestive
enzyme which prevents
food from being digested
and absorbed which can
lead to malnutrition.
How Do People Inherit Cystic Fibrosis?
This condition is inherited in an
autosomal recessive pattern, which
means both copies of the gene in
each cell have mutations. The
parents of an individual with an
autosomal recessive condition
each carry one copy of the
mutated gene, but they typically
do not show signs and symptoms
of the condition.
Sickle Cell Disease
Sickle cell disease is an inherited blood disorder that
affects red blood cells.
People with sickle cell conditions make a different form of
hemoglobin A called hemoglobin S (S stands for sickle). Red
blood cells containing mostly hemoglobin S do not live as long
as normal red blood cells (normally about 16 days). They also
become stiff, distorted in shape and have difficulty passing
through the body’s small blood vessels. When sickle-shaped
cells block small blood vessels, less blood can reach that part
of the body. Tissue that does not receive a normal blood flow
eventually becomes damaged. This is what causes the
complications of sickle cell disease.
Who Is At Risk for Sickle Cell Disease?
Sickle cell disease is most common in people whose
families come from Africa, South or Central America
(especially Panama), Caribbean islands, Mediterranean
countries (such as Turkey, Greece, and Italy), India, and Saudi
Arabia.
In the United States, it's estimated that sickle cell disease affects
70,000–100,000 people, mainly African Americans. The disease
occurs in about 1 out of every 500 African American births. Sickle
cell disease also affects Hispanic Americans. The disease occurs
in more than 1 out of every 36,000 Hispanic American births.
More than 2 million Americans have sickle cell trait.
1. Sickle cells do not carry oxygen efficiently
2. Sickle cells are fragile and break easily.
3. Sickle cells clog blood vessels and reduce
blood flow; this damages tissues and organs
and causes severe pain.
How Do People Inherit Sickle Cell disease?
Phenylketonuria (PKU)
This disease is an inborn error of metabolism. A gene that
codes for an enzyme is missing or defective. In 'classic PKU',
the enzyme that breaks down phenylalanine, phenylalanine
hydroxylase, is completely or nearly completely deficient.
This enzyme normally converts phenylalanine to another
amino acid, tyrosine. Without this enzyme, phenylalanine
and its breakdown chemicals from other enzyme routes,
accumulate in the blood and body tissues which can poison
the brain and cause mental retardation. PKU is inherited in
a recessive fashion. A person with PKU will have the
genotype pp; a carrier will have the genotype Pp. A person
who is not a carrier and does not have the disease has the
genotype PP
About 50% of untreated infants have early symptoms, such
as vomiting, irritability, an eczema-like rash, and a mousy
odor to the urine. Some may also have subtle signs of
nervous system function problems, such as increased
muscle tone, and more active muscle tendon reflexes.
Later, severe brain problems occur, such as mental
retardation and seizures. Other commonly noted features
in untreated children include: microcephaly (small head),
prominent cheek and upper jaw bones with widely spaced
teeth, poor development of tooth enamel, and decreased
body growth. If PKU is detected, a special diet lacking in
phenylalanine is started immediately. The baby must follow
the diet for several years while its brain is developing. After
the brain develops, the child may follow a normal diet.
Individuals with PKU are
treatedwith a special diet low in
phenylalanine
How Do People Inherit PKU?
Tay Sachs
Tay- Sachs disease (TSD) is a fatal, recessive genetic disorder in
that causes progressive destruction of the central nervous
system as waste products accumulate in brain cells.
When a person has Tay-Sachs disease, harmful quantities of a
fatty substance called ganglioside GM2 accumulate in the
nerve cells in the brain. Infants with Tay-Sachs disease appear
to develop normally for the first few months of life. Then, as
nerve cells become distended with fatty material, a relentless
deterioration of mental and physical abilities occurs. The child
becomes blind, deaf, and unable to swallow. Muscles begin to
atrophy and paralysis sets in.
The Tay-Sachs genes are located on chromosome 15;
these are the genes that code for the enzyme Hex-A. In
order for a person to develop Tay-Sachs, they must
receive defective Hex-A genes from both parents (tt). If
they receive a defective gene from only one parent,
they will not develop the disease but will be a carrier of
the disease (Tt). Tay-Sachs occurs significantly high in
Persons of Eastern European (Ashkenazi) Jewish
descent. About one in every 27 Jews in the United
States is a carrier of the Tay- Sach's gene. Recently,
cases of Tay--Sachs have been found among the Cajun
population.
How Do People Inherit Tay Sachs?
Huntington’s Disease
Huntington’s disease is a rare disease that affects
1 in every 25,000 people. It is a lethal (deadly)
disease caused by a dominant gene. Each child
has a 50% chance of inheriting the dominant
gene and developing the disease. Genotypes for a
person with Huntington’s disease Hh, HH.
Remember, if you carry the gene, you have the
disease since it is caused by a dominant gene.
The genotype for a person who does not have
Huntington’s disease is hh.
The symptoms of Huntington's disease usually develop when
people are between 30-50 years old, although they can start
much earlier or much later. The symptoms can also differ from
person to person, even in the same family. Sometimes, the
symptoms are present for a long time before a diagnosis of
Huntington's disease is made. This is especially true when
people are not aware that Huntington's disease is in their
family.
The early symptoms include:
•
•
•
•
•
•
slight, uncontrollable muscular movements
stumbling and clumsiness
lack of concentration
short-term memory lapses
depression
changes of mood, sometimes including aggressive or antisocial
behavior
How Do People Inherit Huntington's Disease?
Autosomal dominant inheritance
pattern.
In an autosomal dominant disorder,
the mutated gene is a dominant gene
located on one of the nonsex
chromosomes (autosomes). You only
need one mutated gene to be affected
by this type of disorder.
Sex-linked gene mutations
In sex-linked traits, the gene for the trait is found on the X
chromosome (a sex chromosome). Sex-linked traits affect primarily
males, since they have only one copy of the X chromosome (male
genotype: XY). Females, who have two copies of the X chromosome,
are affected only if they are homozygous for the trait. Females can,
however, be carriers for sex-linked traits, passing their X chromosomes
on to their sons.
Sex-linked inheritance works as follows: if a female carrier
and a normal male give birth to a daughter, she has a 1 in
2 chance of being a carrier of the trait (like her mother). If
the child is a son, he has a 1 in 2 chance of being affected
by the trait (for example, colorblindness). If a female
carrier and an affected male give birth to a daughter, she
will either be affected or be a carrier. If the child is a son,
he will either be affected or be entirely free of the gene.
Hemophilia
An example of a sex-linked trait is hemophilia, made famous by
The "Queen Victoria pedigree" of the European nobility.
Beginning with Queen Victoria of England (in whom it was
probably a spontaneous mutation), the hemophilia gene spread
quickly throughout the European rulers (who intermarried as a
matter of course). The disease, which prevents blood from
clotting properly and renders a minor injury a life-threatening
event, claimed several young men of the royal line. Especially
since male heirs were preferred over female as successors to the
thrones of Europe, the spread of such a debilitating disease was
a major problem.
Completing sex-linked (x-linked) Punnett squares.
Sex linked traits are traits that are carried on the X chromosome..There are few
sex-linked traits that are dominant.
Genotypes for hemophilia:
Normal female- HH- XH XH (does not have hemophilia, is not a carrier)
Normal female- Hh- XH Xh (does not have hemophilia but is a carrier)
Female with hemophilia- Xh Xh
Normal male – XH Y
Male with hemophilia- Xh Y
A normal male is crossed with a female who is a carrier.
XH Y x XHXh
XH
Y
XH
XHXH
XHY
Xh
XHXh
XhY
A man with hemophilia is crossed with a normal
female.
Genotypes: XhY
XH
XH
Xh
XHXh
XHXh
Y
XHY
XHY
Chromosome Mutations
Chromosome mutations are much more serious
than gene mutations as they involve more genetic
material.
A chromosome abnormality reflects an
abnormality of chromosome number or structure.
Nondisjunction occurs when homologous
chromosomes fail to separate during meiosis. This
can result in genetic disorders in which there are
extra or missing chromosomes.
Numerical Abnormalities:
When an individual is missing either a chromosome from a pair
(monosomy) or has more than two chromosomes of a pair (trisomy).
An example of a condition caused by numerical abnormalities is
Down Syndrome, also known as Trisomy 21 (an individual with Down
Syndrome has three copies of chromosome 21, rather than two).
Down Syndrome (Trisomy 21)
Down Syndrome is caused by an extra
chromosome on the 21st pair. About 1 in 600
babies are born with Down Syndrome. The rate
of cases varies according to the age of the
mother. Mothers < 35, fewer than 1 baby in
1,000. Mothers > than 45, 1 baby in 60. Down
syndrome may result in varying degrees of
mental retardation. In addition, physical features
such as an enlarged tongue and weak muscles
may also result.
Persons with Down syndrome are
living longer than ever before.
Although many children have
physical and mental limitations,
they can live independent and
productive lives well into
adulthood.
Turner’s Syndrome (Monosomy X)
Turner’s syndrome results
from the absence of an X
chromosome on an egg.
Genotype XO. These females
do not mature sexually and
are sterile since their ovaries
are underdeveloped. They
are frequently short and have
a large neck. Hormone
treatments have been proven
to be extremely successful
with these women and some
are even able to bear
children.
Klinefelter’s Syndrome
Klinefelter’s Syndrome occurs as the
result of an error (nondisjunction)
during the formation of an egg or a
sperm that results in a person having a
XXY combination or 47 chromosomes
instead of the normal 46.
The offspring have a genotype of XXY.
These males have reduced fertility and
are often mentally retarded.