Human Genetics: Genetic Disorders

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Human GeneticsGenetic Disorders

• Ms. Y. Martinez
• LSHS
• 07-08

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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.

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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.

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• 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.

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• At the end of meiosis, the chromosomes have
  failed to separate and the gametes have an
  UNEQUAL number of chromosomes

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• 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.

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Trisomy Disorders

• Remember 2n 46
• In a trisomy disorder, a gamete has gained an
  EXTRA chromosome
• So, a trisomic individual has 2n 47

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Trisomy Disorders

• Trisomy 21 (Down or Downs Syndrome)
• Klinefelter (or Klinefelters) Syndrome (Males
  only, XXY Trisomy)

2n 47
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Trisomy 21, Down Syndrome

• Individuals have an extra 21st chromosome
• Usually occurs once in every 800 births

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• People with Down Syndrome

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Characteristics

• Round face
• Extra 21st chromosome
• Short fingers
• Cupped ear
• Protruding tongue
• Mental deficiency

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• Simian Crease in the hand
• Nondisjunction is the cause

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Incidence of Down Syndrome in Newborns (Hook, et
al., 1988)
Maternal Age
Incidence

• 20 24 1 1400
• 25 29 1 1100
• 30 - 34 1 700
• 1 350
• 1 225
• 39 1 140
• 41 1 85
• 43 1 50
• 45 1 25

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Klinefelter Syndrome, XXY Trisomy

• Individuals have an extra X sex chromosome
• Usually occurs once in every 1080 births

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• A male with Klinefelter Syndrome

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• Male reproductive cells do not undergo meiosis
  (sterile)
• Only 40 have breast development
• Intelligence is less than normal
• Nondisjunction is the cause

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Monosomy Disorders

• Remember 2n 46
• In a monosomy disorder, a gamete has LOST a
  chromosome
• So, a monosomic individual has 2n 45

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Monosomy Disorders

• Turner Syndrome, XO (Females Only)
• OR
• Turner Syndrome , X (Females only)

2n 45
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Turner Syndrome, X or XO

• Individuals have only ONE X sex chromosome
• Usually occurs once in every 5000 births

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• A female with Turner Syndrome

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• Female reproductive cells do not undergo meiosis
  (sterile)
• Has webbing of the neck
• Intelligence is less than normal
• Nondisjunction is the cause

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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.

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Examples of Autosomal Dominant Disorders (ex RR,
Rr)

• Huntingtons Disease
• Achondroplasia
• Polydactyly
• Marfan Syndrome

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Huntingtons 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.

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Achondroplasia, DD or Dd
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• 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.

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Characteristics

• short stature
• short arms
• short legs
• a large head

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Polydactyly, DD or Dd

• Polydactyly refers to extra digits - in the hand,
  extra fingers or thumbs.

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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.

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Characteristics

• very tall
• Thin
• Double jointed
• heart and blood vessel problems
• a weak in the aorta

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• President Abraham Lincoln was thought to have
  Marfan Syndrome.
• What do you think?

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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.

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Autosomal Recessive Disorders (ex rr)

• Phenylketonuria (fen-ul-ket-oh-NOOR-ee-uh), , PKU
• Cystic Fibrosis
• Tay-Sachs Disease
• Sickle-cell Anemia
• Albinism

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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/profess
  ionals/14332_1219.asp)

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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.

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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.

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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.

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• Hemoglobin is the protein in red blood cells that
  carries oxygen.
• The normal allele for the gene differs little
  from the sickle cell allelejust 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.

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Albinism, (ex rr)
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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.

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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 sex-linked genes.
• Many sex-linked genes are found on the X
  chromosome.
• Are found more often in Males (XY makeup)

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• 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?____

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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, red-green
  colorblindness, is found in about 1 in 10 males
  in the United States.
• Among females, however, colorblindness is
  rareonly about 1 female in 100 has
  colorblindness. Why the difference?

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• A non-colorblind individual will be able to see
  the number. A colorblind individual will not.

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• A colorblind individual will not see the green
  leaf.
• A non-colorblind individual will it.

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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.

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• 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.

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Duchenne Muscular Dystrophy, XrXr or XrY

•  Duchenne muscular dystrophy (DIS-truh-fee) 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.

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• In Duchenne muscular dystrophy, posture changes
  as the child grows.

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Human Genes

• The human genomeour complete set of genetic
  informationincludes 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.

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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.

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Gene Therapy