Human Genetic Disorders

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• Human Genetic Disorders
• Autosomal Recessive
• Sickle-cell disease
• Single amino acid substitution (valine for
  glutamate) in hemoglobin
• Causes some erythrocytes to form sickle shape
• Abnormal erythrocytes slow blood flow and may
  block capillaries

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• Human Genetic Disorders
• Autosomal Recessive
• Sickle-cell disease
• Single amino acid substitution (valine for
  glutamate) in hemoglobin
• Causes some erythrocytes to form sickle shape
• Abnormal erythrocytes slow blood flow and may
  block capillaries
• Most common in people of African descent (1 in 10
  African Americans is heterozygous sickle cell
  trait)
• Why so common?
• May be advantageous in areas where malaria is a
  problem
• Heterozygous people more resistant to malaria
  than homozygous dominant people

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Fig. 23.17
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Malaria
Sickle Cell Allele Frequency
http//upload.wikimedia.org/wikipedia/commons/1/10
/Malaria_versus_sickle-cell_trait_distributions.pn
g
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http//www.cdc.gov/malaria/about/biology/sickle_ce
ll.html
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• Human Genetic Disorders
• Autosomal Recessive
• Tay-Sachs disease
• Absence in brain of enzyme that helps to break
  down membrane lipids and prevents their
  accumulation
• Accumulation causes brain damage
• Especially common in people of Ashkenazi Jewish
  (Eastern European) descent
• Possibly due to population bottleneck during
  persecution restriction to ghettos in Middle
  Ages

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• Human Genetic Disorders
• Autosomal Dominant
• Achondroplasia
• Abnormal gene on chromosome 4 ? skeletal growth
  disorder ? dwarfism (relatively normal torso,
  short arms and legs)
• Most common growth-related disorder
• Results from inheritance in lt20 of cases
• Huntingtons Disease
• Defective allele ? proteins with long glutamine
  strands
• Affects nervous system ? severe mental and
  physical deterioration ? death
• Typically appears later in life Almost always
  before age 50 but almost never before age 20
• Usually after reproductive age

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• Chromosomal Theory of Inheritance
• Proposed in early 1900s
• Unified understanding of mitosis and meiosis with
  Mendels work on inheritance

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Fig. 15.2
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• Linkage and Recombination
• Linkage
• Alleles dont always assort independently
• Two genes on same homologous chromosome
• Linkage first studied in Drosophila by
  Thomas Morgan (early 1900s)
• Worked with wild type and mutant fruit flies
• Studied inheritance with two-point test cross
  between heterozygous individual and homozygous
  recessive individual

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Fig. 15.9
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• Linkage and Recombination
• Recombination
• Occurs during crossing over in meiosis
• Drosophila example
• F1 parent produced some recombinant gametes

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Fig. 15.10
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• Linkage and Recombination
• Recombination
• Greater distance between genes ? Greater
  probability of recombination
• Distance between two genes expressed in map
  units
• 1 map unit 1 recombination frequency

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Fig. 15.11