1. Basic terms and concepts
2. Examples: PKU, hypercholesteremia, CF, sickle cell
3. The "Central Dogma" -- gene expression
4. Viruses and genes
5. Genes and cancer
 

With 2 neighbors, discuss the following concepts:
Gene – relationship to chromosome, to DNA
Allele -- dominant/recessive/co-dominant/sex-linked
Mutation
 

Genes encode proteins

So: different alleles of the same gene encode different variants of the same protein – “biochemical individuality”

 Example: PKU – phenylketonuria –
   Gene: specifies a protein that helps break down the amino acid phenylalanine – one of the 20 amino acids in all proteins
    If this gene is not functioning: a byproduct builds up that is VERY damaging to the developing brain
    Solution: test all babies soon after birth for this byproduct
    If they have PKU: put them on a controlled artificial diet for the first few years, at least
     Potential problem 1:  Adult with PKU gets pregnant
     Potential problem 2:  Aspartame/ NutraSweet
          ? kids with lower or less effective version of this enzyme?
          Recommended precaution: no aspartame to small kids

Example: hypercholesteremia
      One gene: specifies the low-density-lipoprotein (LDL) receptor
             One nonfunctional copy: LDL levels in the 300’s; heart attacks in the 30’s are common.
             Two nonfunctional copies:  each cell has to make all its own cholesterol because they can't take up cholesterol; joint heart/liver transplants in childhood
 

Example: cystic fibrosis
    Gene: specifies a specific chloride ion channel
 Consequences:
    Many ducts blocked before birth – poor pancreatic enzyme secretion, therefore poor digestion, thin, poor growth; sterile
Partial solution: digestive enzymes with all protein
    Lungs: more basic; mucous builds up; very prone to infections (now: 95% of CF deaths are due to drug-resistant Pseudomonas lung infections)
 Partial solutions: pounding back; DNase spray; ?phage spray;

Example: sickle-cell anemia
         Gene: hemoglobin beta chain – change of a single letter in the DNA code leads to change in a single amino acid.
          That change in the single amino acid on both beta subunits leads the hemoglobin molecules to stick together in chains.  This in turn causes the red blood cells to “sickle” – as we will discuss when we talk about proteins in a couple of weeks.
 “Central Dogma”:

The sequence of nucleotides in the DNA specifies the sequence of amino acids in the protein encoded by a given gene.

        DNA: dG, dC, dA, dT
         RNA:   C,  G,   U,   A
        Protein:  20 different amino acids – so, need a TRIPLET code – and this is just translated 3 at a time from a defined starting point – there are no spaces or punctuation marks.

DNA is the encyclopedia, in 23 pairs of volumes -- so, there are potentially 2 different pieces of information for each entry in our "encyclopedia of life".
 

Messenger RNA (mRNA) is the “xerox copy”, or duplicate tape, of each specific gene/ “recipe” whose product is needed in that particular cell at that particular time
 

Each cell needs each particular ingredient protein at about the right level.  The level can be controlled by controlling the level of transcription – ie, of mRNA synthesis – and the amount of translation of that mRNA, as well as the stability of the final protein product.

Having an extra copy of one chromosome upsets those control mechanisms and is generally lethal or causes problems, as in the case of Down’s syndrome (trisomy of chromosome 21)

 VIRUS:

DNA  or  RNA  in a very specific protein "space ship"

Invade very specific kinds of cells:
     HIV: human helper T lymphocytes
     Hepatitis C: human hepatocytes (liver cells)
     SV40: monkey kidney cells
     Bacteriophages: bacterial cells
 T-even phages: E. coli and Shigella dysenteriae
 

Reprogram the cell to be a factory for making new viruses

Lytic (lead in short order to virus production & cell lysis)
versus temperate (can coexist, often integrated, for an extended time)

Some viruses can be involved in causing cancer