Transcript Human Genetics

Human Genetics:
Genetic Disorders
Ms. Y. Martinez
LSHS
07-08
Genes and the Environment



The phenotype of an organism is only
partly determined by its genotype.
Many traits are strongly influenced by
environmental, or nongenetic, factors,
including nutrition, exercise and
sunlight.
For example, nutritional improvements
in the United States and Europe have
increased the average height of these
populations about 10 centimeters over
their average height in the 1800s.
Human Genetic Disorders

Most of the time, the mechanisms that
separate human chromosomes in meiosis
work very well, but every now and then
something goes wrong.


The most common error in meiosis occurs when
homologous chromosomes fail to separate. This
is known as nondisjunction, which means “not
coming apart.”
If nondisjunction occurs, abnormal numbers
of chromosomes may find their way into
gametes, and a disorder of chromosome
numbers may result.

At the end of
meiosis, the
chromosomes
have failed to
separate and
the gametes
have an
UNEQUAL
number of
chromosomes


After nondisjunction
occurs and a gamete
has one EXTRA
chromosome, a Trisomic
human genetic disorder
can result.
After nondisjunction
occurs and a gamete
has one LESS
chromosome, a
MONOSOMIC human
genetic disorder can
result.
Trisomy Disorders



Remember 2n = 46
In a trisomy disorder, a gamete has gained
an EXTRA chromosome
So, a trisomic individual has 2n = 47
Trisomy Disorders


Trisomy 21 (Down or Down’s Syndrome)
Klinefelter (or Klinefelter’s) Syndrome
(Males only, XXY Trisomy)
2n = 47
Trisomy 21, Down Syndrome


Individuals
have an
extra 21st
chromosome
Usually
occurs once
in every 800
births

People
with
Down
Syndrome
Characteristics






Round face
Extra 21st
chromosome
Short fingers
Cupped ear
Protruding
tongue
Mental deficiency


Simian
Crease in the
hand
Nondisjunction
is the cause
Incidence of Down Syndrome in
Newborns
(Hook, et al., 1988)
Maternal Age
20 – 24
Incidence
1 : 1400
25 – 29
1 : 1100
30 - 34
1 : 700
35
1 : 350
37
1 : 225
39
1 : 140
41
1: 85
43
1: 50
45+
1 :25
Klinefelter Syndrome, XXY Trisomy


Individuals
have an
extra “X” sex
chromosome
Usually
occurs once
in every
1080 births

A male with
Klinefelter
Syndrome




Male reproductive
cells do not
undergo meiosis
(sterile)
Only 40% have
breast
development
Intelligence is less
than normal
Nondisjunction is
the cause
Monosomy Disorders



Remember 2n = 46
In a monosomy disorder, a gamete has
LOST a chromosome
So, a monosomic individual has 2n = 45
Monosomy Disorders



Turner Syndrome, XO
(Females Only)
OR
Turner Syndrome , X
(Females only)
2n = 45
Turner Syndrome, X or XO


Individuals have
only ONE “X”
sex chromosome
Usually occurs
once in every
5000 births

A female with
Turner
Syndrome




Female
reproductive cells
do not undergo
meiosis (sterile)
Has webbing of
the neck
Intelligence is
less than normal
Nondisjunction is
the cause
Autosomal Dominant Disorders
(ex RR, Rr)


Autosomal dominant is one of several
ways that a trait or disorder can be passed
down through families.
If a disease is autosomal dominant, it
means you only need to get the abnormal
gene from one parent in order for you to
inherit the disease. One of the parents
may often have the disease.
Examples of Autosomal Dominant
Disorders (ex RR, Rr)




Huntington’s Disease
Achondroplasia
Polydactyly
Marfan Syndrome
Huntington’s Disease, DD
or Dd


Huntington's disease causes a progressive
loss of muscle control and mental function
until death occurs.
People who have this disease generally
show no symptoms until they are in their
thirties or older, when the gradual damage
to the nervous system begins.
Achondroplasia, DD or Dd



Most people with
achondroplasia are born to
parents of average height,
following a genetic change usually in the sperm.
This particular change - or
mutation - occurs
occasionally when the DNA
is copied in cells that
multiply to make the sperm.
The mutation that causes
achondroplasia is a single
change in the letters of the
DNA code of the FGFR-3
gene.
Characteristics
 short
stature
 short arms
 short legs
 a large head
Polydactyly, DD or Dd

Polydactyly refers to
extra digits - in the
hand, extra fingers
or thumbs.
Marfan Syndrome, DD or Dd
Marfan
syndrome
is a disorder that
affects connective
tissue.
Connective
tissues are
proteins that
support skin,
bones, blood
vessels and other
organs.
Characteristics





very tall
Thin
Double jointed
heart and blood vessel
problems
a weak in the aorta


President
Abraham
Lincoln was
thought to have
Marfan
Syndrome.
What do you
think?
Autosomal Recessive Disorders (ex rr)


Autosomal recessive is one of several
ways that a trait, disorder, or disease can
be passed down through families.
An autosomal recessive disorder means
two copies of an abnormal gene must be
present in order for the disease or trait to
develop.
Autosomal Recessive Disorders
(ex rr)





Phenylketonuria (fen-ul-ket-oh-NOOR-ee-uh), , PKU
Cystic Fibrosis
Tay-Sachs Disease
Sickle-cell Anemia
Albinism
Phenylketonuria, PKU, (ex rr)



Phenylketonuria (PKU) is a genetic
disorder that is characterized by an
inability of the body to utilize the essential
amino acid, phenylalanine.
Phenylalanine is an amino acid found in
milk and many other foods.
If it goes untreated, it causes “mental
retardation.”
(http://www.marchofdimes.com/professionals/14332_1219.asp)
Cystic Fibrosis, (ex rr)



Is a common genetic disease that is most
common among people whose ancestors
came from Northern Europe.
The disease is caused by a recessive allele
on chromosome 7.
Children with cystic fibrosis have serious
digestive problems. In addition, they
produce a thick, heavy mucus that clogs
their lungs and breathing passageways.
Tay-Sachs Disease, (ex rr)



Is caused by an allele found
mostly in Jewish families of
central and eastern European
ancestry.
Tay-Sachs disease results in
nervous system breakdown and
death in the first few years of
life.
Although there no treatment for
Tay-Sachs disease.
Sickle Cell Disease





Is a common genetic disorder found in African
Americans.
Is characterized by the bent and twisted shape of the
red blood cells.
These sickle-shaped red blood cells tend to get stuck in
the capillaries, the narrowest blood vessels in the body.
As a result, blood stops moving through these vessels,
damaging cells, tissues, and organs.
Sickle cell disease produces physical weakness and
damage to the brain, heart, and spleen. In some cases,
it may be fatal.




Hemoglobin is the protein
in red blood cells that
carries oxygen.
The normal allele for the
gene differs little from the
sickle cell allele—just one
DNA base is changed.
This change substitutes
the amino acid valine for
glutamic acid.
As a result, the abnormal
hemoglobin is somewhat
less soluble than normal
hemoglobin.
Albinism, (ex rr)
Albinism, (ex rr)



Is an inherited condition present at birth,
characterized by a lack of pigment that
normally gives color to the skin, hair, and
eyes.
Many types of albinism exist.
The condition, which is found in all races,
may be accompanied by eye problems and
may lead to skin cancer later in life.
Sex-Linked Recessive Disorders
(ex XrXr or XrY)




Sex-linked diseases are inherited through one of
the "sex chromosomes" -- the X or Y
chromosomes.
Because these chromosomes determine sex,
genes located on them are said to be sexlinked genes.
Many sex-linked genes are found on the X
chromosome.
Are found more often in Males (XY makeup)





If mom is a
carrier and dad
is normal, what
chance will:
their daughters
be carriers?___
their daughters
express the
disorder?____
their sons
express the
disorder?____
their sons be
carriers of the
disorder?____
Colorblindness, XrXr or XrY




The gene associated with color vision is located
on the X chromosome.
In males, a defective version of this gene
produces colorblindness, an inability to
distinguish certain colors.
The most common form of this disorder, redgreen colorblindness, is found in about 1 in 10
males in the United States.
Among females, however, colorblindness is
rare—only about 1 female in 100 has
colorblindness. Why the difference?

A noncolorblind
individual
will be able
to see the
number. A
colorblind
individual
will not.


A colorblind
individual will
not see the
green leaf.
A noncolorblind
individual will
it.
Hemophilia, XrXr or XrY




In hemophilia, a protein necessary for normal
blood clotting is missing.
About 1 in 10,000 males is born with a form of
hemophilia.
People with hemophilia can bleed to death from
minor cuts and may suffer internal bleeding from
bumps or bruises.
Hemophilia can be treated by injections of
normal clotting proteins, which are now
produced using recombinant DNA.

Czar Nicholas II of
Russia and his family,
photographed c.
1916, showing his
wife Alexandra (who
was a carrier of
hemophilia), his four
daughters, and (in
the foreground) his
son Alexis, perhaps
the most famous
European royal with
hemophilia.
Duchenne Muscular Dystrophy,
XrXr or XrY


Duchenne muscular dystrophy (DIS-truhfee) is a sex-linked disorder that results in
the progressive weakening and loss of
skeletal muscle.
In the United States, one out of every
3000 males is born with this condition.

In
Duchenne
muscular
dystrophy,
posture
changes
as the
child
grows.
Human Genes



The human genome—our complete set of genetic
information—includes tens of thousands of genes.
The DNA sequences on these genes carry
information for specifying many characteristics, from
the color of your eyes to the detailed structures of
proteins within your cells.
The exploration of the human genome has been a
major scientific undertaking. By 2003, the DNA
sequence of the human genome was complete.
Gene Therapy


In gene therapy, an absent or faulty
gene is replaced by a normal,
working gene.
Why? So the body can make the correct
protein or enzyme it needs, which
eliminates the cause of the disorder.
Gene Therapy