Chapter 4 Flashcards
Genes encode
Proteins (mostly)
Some produce functional RNAs (t and r)
Garrod’s Hypothesis of Inborn Errors of Metabolism
Concluded AKU is genetically determined
Showed that AKU results from HA in urine; termed this an inborn error of metabolism (now known they lacked enzyme)
First evidence of a specific relationship between genes and enzymes
Alkaptonuria
AKU
Characterized by urine blackening on exposure to air and arthritis later in life
Results from homogentisic acid (HA) in urine due to lack of necessary enzyme
One Gene-One Enzyme Hypothesis
Beadle and Tatum
Showed direct relationship between genes and enzymes
Believed metabolism proceeds by series of reactions, each catalyzed by an enzyme and organized into pathways
One gene encodes one enzyme
Now stated as one gene one polypeptide.
What organism did Beadle and Tatum work with?
Neurospora crassa
Mutated WT conidia with xrays and crossed them with WT strain
Germinated in complete medium to ensure growth, then some transferred to minimal media, tested on an array of media to determine type of nutritional mutation
Defective in tryptophan
Prototroph
Strain that grows on minimal media
Auxotroph
Nutritional mutatnt that does not grow on minimal media (requires supplement)
Used auxotrophs in experiment
Pleiotrophy
Multiple phenotypic traits from a single mutation
PKU and Albinism
PKU
Autosomal recessive mutation preventing conversion of phenylalanine into tyrosine
Pleiotropic: causes mental retardation, slow growth, and death; also fair skin, blue eyes, fatigue, and muscle weakness
Albinism
Autosomal recessive mutation in gene for tyrosinase
Can’t convert Tyrosine to DOPA
Light skin, hair, red eyes
Lesch-Nyhan Syndrome
Recessive mutation, X-linked
Found mostly in males
Purines accumulate and converted to uric acid, leads to crystals in joints, kidneys, CNS, and other tissues
Pleiotropic: kidney failure, involuntary spasms, mental deficiency, and self-mutilation
Most die before 20s
Tay-Sachs Disease
Common in Ashkenazi Jewish, Cajuns, and Quebecois
Autosomal recessive mutation
Unprocessed gangliosides in brain accumulate: destroy brain and nerve cells, blindness, hearing loss, and paralysis by age 2
Death by 3-4
Sickle-Cell Anemia
RBCs change shape under low O2 tension
Break easily, less flexible, form blocks in capillaries and tissue damage downstream
Pleiotropic: damage to extremities, heart, lungs, brain, etc. Heart failure, pneumonia, paralysis
Studied with electrophoresis
Hemoglobin structure
4 polypeptide chains: 2 alpha and 2 beta, each with heme group
Valine instead of Glutamic acid in Beta chain
Cystic Fibrosis
Homozygous autosomal mutation
Abnormal protein that results in reduced Chloride channels in cell membrane, preventing Cl- transport
High Cl- levels dehydrates mucus and makes sweat really salty
Thick mucus supports bacterial growth and clogs organs
Amniocentesis
Sample amniotic fluid using a syringe to get shed fetal cells
Chorionic Villus Sampling
Sampling of chorion membrane around fetus via vagina
More risky but can be performed earlier
Cell Free fetal DNA test
New
Very early detection
Maternal blood test
Cheaper, but not available for much
Preimplantation Genetic Diagnosis
Allows people to avoid producing child with disorder
In vitro fertilized embryos grow to 8 or 16-cell stage
One cell removed from each embryo for testing
