Genes and Genetic Defects

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Genes and Genetic Defects

• In which we examine normal genetic transmission
  and genetic defects.

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Part 1 Genes
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Genes and DNA

• A gene is the unit of heredity.
• A gene contains hereditary information encoded in
  the form of DNA, which is located at a specific
  position on a chromosome.
• Genes determine many aspects of anatomy and
  physiology by controlling the production of
  proteins.

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Genotype Phenotype

• Allele Any of the alternate forms of a given
  gene. A gene is a code that produces a protein.
  The alternate forms of a gene produce slightly
  different proteins.
• The alleles for blood type are A, B, and O.
• Genotype The pair of alleles for a given gene.
• The six possible genotypes for blood type are
• AB BB
• AA BO
• AO AO

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Genotype Phenotype

• Phenotype The physical trait produced by a
  genotype.
• The genotypes for blood type and their
  phenotypes are
• genotype phenotype
• AB AB
• AA A
• AO A
• BB B
• BO B
• OO O

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Dominant Recessive Alleles

• Dominant produces the same phenotype whether it
  is paired with same or different allele
• Recessive produces the same phenotype only if
  it is paired with the same allele
• Codominant when neither of two alleles dominate
  the other
• For blood type A is dominant over O
• B is dominant over O
• therefore, O is recessive
• A and B are codominant

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Why do some alleles dominate over others?

• A gene contains code for producing a protein.
• The different alleles for a gene produce slightly
  different versions or different amounts of that
  protein.
• Note some alleles are code that fail to produce
  the protein. (e.g., hemophilia)
• The protein produced by one allele may be
  stronger than the protein produced by other
  alleles. The allele producing the stronger
  protein is dominant.

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Example of proteins

• The exact color of the human eye is determined by
  the amount of a single pigment called melanin
  that is present in the iris of the eye.
• Melanin is a dark brown pigment that is deposited
  on the front surface of the iris.
• If a lot of melanin is present, the eye will
  appear brown or even black.
• If very little melanin is present the iris
  appears blue.
• Intermediate amounts of melanin produces gray,
  green, hazel or varying shades of brown.

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Some Examples of Dominance
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More Examples
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Heterozygous Homozygous

• Rh factor a protein found on the surface of red
  blood cells, which produces an antigenic reaction
• There are 2 alleles for the Rh factor
  (produces the protein) and - (does not produce
  protein)
• is dominant over -
• Genotype Phenotype
• Homozygous Dominant Rh
• - - Homozygous Recessive Rh-
• - Heterozygous Rh

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Part 2 Genetic Defects
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What is a Genetic Disorder?

• Genetic disorder a disorder that is caused by
  a a faulty allele that programs the body to be
  built in a maladaptive way.
• Hemophilia normal allele produces proteins that
  cause the blood to clot faulty allele does not
  produce the blood-clotting proteins.
• Sickle Cell Anemia the faulty allele causes a
  mutation of a blood protein (beta globin), which
  in turn causes red blood cells to be
  sickle-shaped, stiff, and sticky, which cause
  severe organ damage.

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Types of Genetic Disorders

• Genetic disorders carried on the autosomes
• Dominant genetic disorder A genetic disorder
  in which the faulty allele is dominant. A person
  with just one faulty allele will have the
  disorder.
• Recessive genetic disorder A genetic disorder
  in which the faulty allele is recessive. Only
  people with two faulty alleles will have the
  disorder.
• Genetic disorders carried on the X chromosome
• Sex-linked genetic disorder The faulty allele
  is recessive. A female must have two faulty
  alleles in order to have the disorder a male
  will have the disorder with only one faulty
  allele.

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Dominant Genetic Disorders

• Caused by a gene on one of the autosomes, the
  faulty allele is dominant.
• Anyone who has the faulty allele will get the
  disorder.
• Genotype Phenotype
• D D Homozygous Dominant has disorder
• N N Homozygous Recessive normal
• N D Heterozygous has disorder
• N normal allele, D faulty allele

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Examples of Dominant Disorders

• Huntingtons Chorea faulty allele produces an
  abnormal protein that in middle age begins to
  destroy brain cells that control movement. (1 in
  10,000 births)
• Adult Polycystic Kidney Disease faulty allele
  results in growth of fluid-filled cysts in
  kidneys, which replace healthy tissue and
  eventually cause kidney failure and death.
• Neurofibromatosis faulty allele results in
  growth of benign tumors on nerve cells throughout
  body. (1 in 2500 births)

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Example 1 Parents NN NN
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Example 2 Parents NN ND
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Example 3 Parents ND ND
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Recessive Genetic Disorders

• Caused by a gene on one of the autosomes, the
  faulty allele is recessive.
• Anyone who has the faulty allele will get the
  disorder.
• Person with one faulty allele will not have
  disorder, but will be a carrier.
• Genotype Phenotype
• N N Homozygous Dominant normal
• D D Homozygous Recessive has disorder
• N D Heterozygous carrier
• N normal allele, D faulty allele

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Examples of Recessive Disorders

• Sickle Cell Anemia found in populations
  descended from Africa. Incidence among
  African-Americans, 1 in 375 births.
• Tay-Sachs Disease faulty allele does not
  produce protein needed to break down gangliosides
  in nerve cells, which accumulate and destroy the
  nerve. Incidence among Ashkenazi Jews, 1 in 27
  are carriers. General population, 1 in 250 are
  carriers.

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Another Example

• Phenylketonuria faulty allele that produces
  mutated enzyme, which in turn fails to metabolize
  phenylalanine, which accumulates in the brain,
  causing retardation and epilepsy.
• PKU test blood test given to infants shortly
  after birth to determine if there is abnormally
  high level of phenylalanine in the blood.
• Incidence U.S. Caucasians, 1 in 8,000. U.S.
  Blacks 1 in 50,000.Irish, 1 in 4500. Japanese,
  1 in 143,000. Countries with low immigration
  from Celtic countries have low rates in
  Phenylketonuria.

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Example 1 Parents NN NN
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Example 2 Parents NN ND
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Example 3 Parents ND ND
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Example 4 NN DD
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Sex-Linked Genetic Disorders

• Caused by a gene on the X chromosome, the faulty
  allele is recessive.
• Males who have the faulty allele in their X
  chromosome will have the disorder
• Females who have the faulty allele on one X
  chromosome will be carriers those who have the
  faulty allele on both X chromosomes will have the
  disorder.

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How do we know the faulty allele is on the X
chromosome?
Traits on X chromosome
Traits on Y chromosome
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Besides male sex determining gene, only other
trait found on Y chromosome
Come to class to see slide!
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Sex Differences in Sex-Linked Genetic Disorders

• Y chromosome only has genes for male sex
  differentiation (and hairy ears).
• Therefore, for all traits on X chromosome, males
  have only one gene. The single allele of a gene
  determine phenotype for males
• Genotype Phenotype
• XNY normal
• XDY disorder

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Sex Difference, continued

• Females have two X chromosomes. Thus, for all
  traits on X, females have two genes.
• Disorders on X are recessive. Therefore, to have
  disorder, females must have two faulty alleles.
  A female with one faulty and one normal allele
  is a carrier.
• Genotype Phenotype
• XN XN normal
• XN XD carrier
• XD XD disorder

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Examples of Sex-Linked Disorders

• Hemophilia faulty allele is mutation of
  blood-clotting gene. Persons with disorder have
  blood that clots very slow or does not clot at
  all. Incidence 1 in 4000 males, 1 in 16,000,000
  females.
• Duchenne Muscular Dystrophy faulty allele fails
  to produce muscle protein, dystrophin, the lack
  of which causes muscle cells to die. 70 of
  cases are inherited, 30 are spontaneous
  mutations. Incidence 1 in 3500 males, 1 in
  12,500,000 females (theoretical).

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Example 1 XNXN XNY
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Example 2 XNXD XNY
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Example 3 XNXN XDY
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Example 4 XNXD XDY
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Chromosomal Abnormalities vs. Genetic Defects