Meet The Fugates

“The Blue People of Kentucky”

• Where: Troublesome Creek Kentucky

• Who: Fugates & Smith Clans

• What: Intermarriage produces first blue Fugate in 1832

Why?

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

Why So Common In Fugate-Smith Clan?

Fugate Pedigree

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

Orkney Islands

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)

Why So Common In Orkney Island Fishermen?

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

Cause of Williams-Beuren Syndrome

• Deletion on 26 genes on chromosome 7

Why Does Williams-Beuren Syndrome Persist To This Day?

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

Why More New Mutations Found In European Populations Than In African Populations?

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

Point Mutation-Sickle Cell Anemia

Why?

• Alio Nhunte Ri Nth Ejungl Edar• Kan Dac Hines Edentis• Tan Dab Ritis Hquee

• Nal Lfi Ttogethe• R

Chromosomal Mutations

Translocations of the SRY Gene

SRY Gene Mutations and Athletics