Three Steps of Taysachs Disease

1. Brain cells are unable to metabolize gangliosides (a type of lipid) because an enzyme is defective.
2. Lipids accumulate, shutting down neurons.
3. Inflicted individual dies.

Details of Taysachs Disease

To be inflicted a person must be homozygous. It is a recessive trait BUT at the biochemical level there is incomplete dominance:  in heterozygotes, there is an intermediate activity level for that enzyme.  Heterozygotes lack symptoms because having 50% of the normal functioning enzymes is sufficient to keep lipid concentration below critical levels.  Actually, heterozygotes are producing normal enzymes half the time and defective enzymes the other half of the time (very important!  This is codominance on the macromolecular level).

Cystic Fibrosis

• One out of 28 (4%) is a carrier and 1 out of 2500 Caucasians is affected.
• The normal allele codes for a membrane protein that functions in chloride transport between certain cells and the extracellular fluid (EC fluid).
• The recessive allele causes defective or absent chloride channels in the plasma membrane resulting in abnormal concentrations of EC chloride that causes mucus to build up (stickily and thickly) in the pancreas, lungs, and digestive tract, favoring bacterial infections such as pneumonia.

Sickle-cell anemia

• Most common recessive disorder:  1/400 African-Americans are affected, 1/10 is a carrier.
• It is caused by a single nucleotide substitution that changes one amino acid in the hemoglobin protein of red blood cells.  When blood dissolved oxygen concentration is low, the hemoglobin can turn red blood cells into sickle shapes (see pleiotropy).  In heterozygotes, it is codominant at the molecular level; heterozygosity increases malarial resistence.

Taysachs, cystic fibrosis, and sickle-cell anemia are examples of recessive disorders where the responsible allele codes for a malfunctioning protein or no protein at all.  Heterozygotes are carriers of these disorders.

Examples of Dominant Disorders

1. achondroplasia, aka dwarfism
   1. 1 in 10000 is affected
   2. Homozygosity leads to spontaneous abortion by the fetus.
2. Huntington's disease
   1. degenerates the nervous system
   2. There is no phenotypic effect until ages 35 or 40, then deterioration begins.

Multifactorial Disorders

genotype + environment = disease	includes heart disease, cancer, diabetes, alcoholism, schizophrenia, manic-depressive psychosis
In many cases the hereditary component is polygenic.

Chronic Villus Sampling (CVS)

Fetal tissure is obtained from the placenta.  Karyotyping of fetal chromosomes determines genetic health of the baby.  CVS can be performed in the 8th or 10th week.

Next:  "Chromosomal Basis of Inheritence."