Human Genetics

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Human Genetics
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Human Genetic Disorders
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The following conditions are caused by mutant
recessive genes

• Albinism recessive gene that results in a lack
  of an enzyme to produce a pigment called melanin.
  An albino lacks pigment in the hair and skin and
  has either pink or pale blue eyes.

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PKU

• a recessive gene that results in the inability to
  make an enzyme needed for changing the amino acid
  phenylalanine to tyrosine. Phenylalanine builds
  up in the bloodstream, is harmfull to brain cells
  and eventually will cause mental retardation. PKU
  is detected in newborns by a blood test. Mental
  retardation can be prevented if the affected baby
  is placed on a special diet that restricts
  phenylalanine intake for the first few years.

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Cystic Fibrosis

• a recessive gene that alters a protein that
  regulates the normal movement of salt in and out
  of cells.
• This results in thick sticky secretions in the
  respiratory and digestive tracts.
• Most common in Caucasians.

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Tay-Sachs

• a recessive gene that results in the inability to
  synthesise the enzyme that prevents lipid buildup
  in the brain. As lipids collect, the nervous
  system begins to break down. No known cure, it is
  a lethal gene. Most common in Jewish and Eastern
  European ancestry.

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Sickle Cell Anemia

• a recessive gene that affects the ability of red
  blood cells to carry oxygen.
• Affects 1 in 350 African Americans.
• Hemoglobin is the oxygen-carrying chemical in red
  blood cells. The abnormal hemoglobin, called
  hemoglobin S differs from the normal hemoglobin
  (hemoglobin A) by only one amino acid.
• The mutant gene differs from the normal gene by
  only one nucleotide.
• he RBC s of a person with sickle cell convert to
  sickle shape when the body is, which a poor
  oxygen carriers, are fragile and tend to block
  small blood vessels and cause swelling and pain.
• Hybrids (carriers) do not suffer from the
  disease, but may have some sickling of RBCs.
• A benefit of being a carrier is that carriers are
  more resistant to malaria.

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Huntingtons Disease

• caused by a single DOMINANT allele.
• Symtoms do not appear until affected people are
  in their late 30s or 40s, when gradual damage
  of their nervous system begins. They suffer from
  a painful progressive loss of muscle control and
  mental function until death occurs. Due to late
  onset this disease is unknowingly passed on from
  generation to generation.

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Nondisjunction

• Turners Syndrome(XO) results from
  nondisjunction of the sex-chromosomes. These are
  females who are short and have characteristic
  neck folds.

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Sex-linked Conditions (Traits)

• Sex-linked Traits Genes that are carried on the
  X chromosome. Most sex-linked traits are
  recessive. Remember that a male only has 1 X
  chromosome (XY) and a female has 2 X
  chromosomes(XX).
• For a male to get the disorder he only has to get
  one recessive allele.
• For a female to get the disorder she has to get 2
  recessive alleles.
• A hybrid female is normal, but a carrier of the
  disease.
• Examples of sex-linked conditions
  colorblindness, hemophilia, muscular dystrophy
  and ALD.

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Sex-linked Conditions

• Colorblindness sex-linked recessive condition in
  which people dont make some of the pigments in
  the eye that are necessary for color vision. The
  most common form is red-green
• colorblindness

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Detecting Colorblindness
Color vision deficiency is usually detected using
colored charts called the Ishihara Test Plates.
The plates consist of gray and colored dots. The
patient is asked to identify the number in the
middle of the circle. After the patient has
identified what they see, more testing may
commence.
Vision test examples.Normal people should see
74. Color deficient people may see D21.
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How are Tests Made?

• A random pattern of gray level dots is first put
  together.

• A digit pattern is then added which is defined by
  yellow/blue variation only. Since most people
  with red/green colorblindness can see yellow/blue
  they will be able to see the digit 5 in this test
  pattern.

• Another digit pattern which is defined by
  red/green variation is added. Here is the
  pattern composed of the random brightness pattern
  and the red/green pattern.

• Finally all three are added People with
  red/green deficiency will not be able to see the
  red/green pattern and will see the 5. People with
  normal vision will see both the patterns, but
  since the red/green is stronger than the
  yellow/blue, the normal person will see the digit
  6.

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What's it Like Being Colorblind?
Most color-blind people see normally in all other
aspects other than the color of their weakened
cone. Color-blind people can usually learn by
experience to associate certain colors with
different sensations of brightness. Many victims
of the defect are unaware that they are
color-blind.
Weak green cone
Weak red cone
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Do sample problems 1. A color blind male marries
a female with normal color vision(with no CB in
her family). What percentage of her daughters
will be expected to be carriers? 2. A male with
normal color vision marries a female that is a
carrier, but has normal color vision. What
percentage of their boys will be expected to be
colorblind?
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Sex-Influenced Traits A trait that is expressed
different in males that females. Example
Baldness Many traits which seem to be sex-linked,
such as male pattern baldness, are actually
caused by genes located on autosomes, NOT
sex-chromosomes. B Normal hair b
Baldness BB Normal in both male and females Bb
Normal in a female, but due to testosterone it
is expressed as bald in a male. bb
Bald in both males and females
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Sex-linked Conditions

• Hemophilia bleeders disease sex-
• linked recessive disease, unable to
• make antihemophiliac factor (AHF) that
• is necessary for blood to clot.
• Do a sample problem
• 1. A hemophiliac male marries a female whose
  mother was hemophiliac. What percentage of their
  girls will be expected to be hemophiliac??

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Hemophilia The Royal Disease
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Muscular Dystrophy (MD) sex-linked recessive
disease that results in progressive wasting away
of skeletal muscle. Caused by a defective protein
known as dystrophin.
Mattie
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Sex-linked Conditions

• ALD (Lorenzos oil) sex-linked recessive disease
  that shows up between ages 4-10 and affects the
  brain They dont make an enzyme that breaks down
  saturated fatty acids. This causes the myelin
  sheath that surrounds neurons to be stripped
  away(demyelination), which inhibits the nerves
  ability to conduct impulses. Symptoms include
  neurological problems such as visual and auditory
  problems, impaired coordination, dementia and
  seizures.

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GENE SEQUENCE
MUTATIONS
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Gene Location

• Chromosome Xq28 Recessive

-ALD is an X-linked disorder, which means it
affects mostly males and is transmitted by a
female carrier. Such disorders are referred to as
"X-linked" since the genetic abnormality involves
the X-chromosome.
X-ALD is a peroxisomal storage disease whereby
abnormal function of peroxisomes leads to the
accumulation of very long-chain fatty acids
(VLCFA) in tissues of the body, especially the
brain and the adrenal glands.
This gene is located on the X-chromosome (its
official name is the ABCD1 gene).
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What to look for in a karyotype?

• 1. Are there 46 chromosomes?
• 2. Are there 2 identical pairs of each
  autosome and 2 sex chromosomes?
• 3. Are there any rearrangements between
  chromosomes or large deletions?

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Down Syndrome( Trisomy 21)

• results from nondisjunction of autosomes 21.
  There is an extra copy of the 21 chromosome.
• In mothers under 30 it occurs about 1 in 1,500
  births, mothers over 45 the incidence rises to 1
  in 16 births.
• effects of Down Syndrome vary greatly from person
  to person but can include mild to severe mental
  retardation, eyes that slant upward, and heart
  defects.

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Down Syndrome
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Kleinfelters (XXY)

• results from nondisjunction of the
  sex-chromosomes.
• Develop as males who are sterile
• often tall and usually do not develop secondary
  sex characteristics such as facial hair, or
  underarm and pubic hair.

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Turner syndrome (XO)

• results from nondisjunction of the
  sex-chromosomes.
• Symptoms include
• short stature
• lack of ovarian development
• webbed neck
• arms that turn out slightly at the elbow
• low hairline in the back of the head

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Prenatal Diagnosis

• Ultrasonography uses high-frequency sound waves
  to produce an image on a monitor. This allows the
  doctor to determine the position of the fetus and
  fetal abnormalities

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Amniocentesis

• Insertion of a needle into the amniotic sac,
  removing some amniotic fluid which contains cells
  from the fetus. The cells are cultured for a few
  days to get enough cells. A Karyotype is then
  prepared to check for chromosomal alterations.
  The cells are also screened for certain chemicals
  that indicate genetic disorders.

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Chorionic Villus Biopsy

• Cells are removed from the placentia surrounding
  the embryo. Results are obtained more quickly
  than by amniocentesis because enough cells are
  obtained without having to culture the cells.
  Studies show that before the 10th week of
  pregnancy limb defects can result.