Part 3

• 1930s Landauer and Dunn reported the following in chickens:

  • Creeper hen x creeper rooster gave 2 creeper:1 normal
• Homozygous C'C' is lethal and creeper chickens are C'C
• If you could find something different than what Mendel said, it was easy to get published
• dominant lethals: a gene that if homozygous for a mutant allele is lethal, but in heterozygotes has an intermediate phenotype
• well known dominant lethals:

  • tailless mice
  • white horses
  • powder puff dogs
  • yellow leaves in snapdragons
  • achondroplastic dwarfism
• 2/3 affected:1/3 normal
• legends for lethals:

  • L'L' lethal
  • L'L unusual "affected" phenotype
  • LL normal
• Recessive lethals generally show no effect in heterozygotes
• recessive lethal genes:

  • vp mutants in maize lack carotenoids so cannot survive when homozygous
  • Tay-Sachs infants do not survive beyond 3 years of age
  • cystic fibrosis is the most common example in Caucasians
• "conditional lethals" can be extremely valuable in genetic research

  • mutations to alleles that are temperature sensitive, or that allow survival on one medium but not another make it possible to study events and genes involved in development, formation of macro-molecular structures, etc
  • heterozygous advantage in sickle cell anemia
• cystic fibrosis:

  • 1 in 24 have it
  • thick mucus clogs lungs and prevents secretion of digestive enzymes from the pancreas
  • very prone to infections
• Huntington disease

  • progressive loss of controlled movement
  • neurodegenerative disorder; loss of cognitive function
  • depression and agression
  • death 10-15 years after symptoms start
  • single gene dominant inheritance
• Symptoms can get worse as the disease passes down to generations
• pleiotropy

  • multiple organs/phenotypes affected
  • may be recessive
  • untreated leads to low IQ, enlarged liver, and cataracts
  • may be dominant
  • skin "bumps", "lumpy" tongue, thyroid defective, intestinal polyps, mucosal defects, cancer prone
• Galactosemia is caused by the inability to get rid of galactose
• Brittle bones occur due to variable expressivity
• Different mutations in each gene means that different defective alleles contribute to variable expressivity. Since defects in different genes may be involved, the trait also demonstrates "genetic heterogeneity" where the same phenotype can result from defects in different genes
• Genetic heterogeneity: defects in different genes can cause the same phenotypes
• pleiotropy: when multiple organs are involved; often seen as a syndrome
• multiple alleles: there are many known mutations in each collagen gene, each technically being a different allele
• compound heterozygotes: individuals carry two different defective alleles; it is often not possible to predict the severity of symptoms in these cases
• lack of penetrance: the variability of expression may be so great that no symptoms are visible at all
• phenocopy: an environmental cause can mimic a gene defect
• epistasis: one gene or genotype masks expression of another
• diploid individuals can have at most two different alleles of any gene
• self protection via acquired immunity:

  • the ability to make specific antibodies is acquired
  • antibodies bind to antigens and target them for destruction
  • antibodies function against microbes, foreign tissues, abnormal cells
  • very few antigens enter via the digestive tract
  • antibodies are gene products
• 1 microliter of blood contains:

  • 5x10^6 red blood cells
  • contains hemoglobin to transport oxygen
  • 3x10^5 platelets
  • for clotting
  • 4,500-11,000 white blood cells
  • B cells that make antibodies
  • T cells for cellular/tissue recognition
  • macrophage cells
• antibodies

  • as it matures, each B cell makes one specific antibody
  • each antibody is made of one heavy and one light chain of amino acids, in pairs
  • the variable portion recognizes and binds to a specific epitope
  • antibody-bound targets are destroyed by other cells
• epitope: a small part of a "foreign" antigen
• Gamma globulin is the most common type of antibody
• There are 2 co-dominant blood group alleles: L^M and L^N
• Any donor tissue with any allele that differs from those present in a recipient will be rejected
• Parents are unlikely to be donors as only one of their chromosomes ends up in the child
• Identical twins are perfect matches for an organ transplant