“The Blue People of Kentucky”
• Where: Troublesome Creek Kentucky
• Who: Fugates & Smith Clans
• What: Intermarriage produces first blue Fugate in 1832
Hemoglobin
• Hemoglobin A is a tetramer with alpha globular proteins
• Each protein containing a porphyrin ring w/ iron+2 ions
• Oxyhemoglobin = red
Methemoglobinemia
• Hereditary Methemoglobinemia (H-met) caused by passage of a mutated gene to offspring
• Due to changes in quaternary level of hemoglobin structure, RBC refuses to release oxygen to the cells
Changes In Frequency• The railroad brought new people to Troublesome
Creek while other natives left• The blue condition began to disappear as the
mutated gene spread to families where it was paired with normal genes for hemoglobin
Fish Odor Syndrome
• Body constantly secretes powerful odor of rotting fish
• Highest frequency of people with this condition isolated on Orkney Islands
Trimethylamineuria
• Gene identified in 1997 for gene FMO3
• Disease state caused by inheritance of two mutated copies of FMO3 gene (located on chromosome 1)
Cleidocranial dystosis
• Noted by lack of collarbone, permanent soft spots in skull and supernumerary teeth
• Caused by mutations in the CBFA2 gene of chromosome 6
• Produced when one copy of gene has mutation and other copy is normal
Williams-Beuren Syndrome
• Elvin ears and facial structure/short stature
• Often lack of ability to read or write clearly
• Frequently, musical, story-telling and social ability enhanced
• Aortic stenosis and hypercalcemia
Mutation: Key Points• Any change in DNA sequence
– Any nucleotide has 1: 1x109 chance of changing
• Changes may occur during replication or after (de novo)
• Mutations may lead to changes in A.A. sequence.
• Not all changes in DNA sequence will translate into an altered amino acid sequence– Wobble Position
• Neutral or beneficial mutations may be passed to future generations, but only if the original mutation is in a germ-line cell
• Negative or somatic mutations are not heritable
Point v. Frameshift Mutations
• Point Mutation• One change in DNA template• One mRNA codon affected
• Frameshift Mutation• Caused by insertion or deletion of base in
DNA template• All mRNA codons shifted ahead or behind