4. Meet The Fugates

5. “The Blue People of Kentucky” Where: Troublesome Creek Kentucky Who: Fugates & Smith Clans What: Intermarriage produces first blue Fugate in 1832

6. Why?

7. Hemoglobin Hemoglobin A is a tetramer with alpha globular proteins Each protein containing a porphyrin ring w/ iron +2 ions Oxyhemoglobin = red

8. 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

10. Why So Common In Fugate-Smith Clan?

11. Fugate Pedigree

12. 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

13. Orkney Islands

14. Fish Odor Syndrome Body constantly secretes powerful odor of rotting fish Highest frequency of people with this condition isolated on Orkney Islands

15. Trimethylamineuria Gene identified in 1997 for gene FMO3 Disease state caused by inheritance of two mutated copies of FMO3 gene (located on chromosome 1)

16. Why So Common In Orkney Island Fishermen?

18. 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

20. 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

21. Cause of Williams-Beuren Syndrome Deletion on 26 genes on chromosome 7

22. Why Does Williams-Beuren Syndrome Persist To This Day?

23. Mutation: Key Points Any change in DNA sequence –Any nucleotide has 1: 1x10 9 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

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

25. 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

28. Point Mutation-Sickle Cell Anemia

30. Why?

31. Alio Nhunte Ri Nth Ejungl Edar Kan Dac Hines Edentis Tan Dab Ritis Hquee Nal Lfi Ttogethe R

33. Chromosomal Mutations

34. Translocations of the SRY Gene

35. SRY Gene Mutations and Athletics