Genetics: It’s in your Blood Hemoglobin Workspace to Illustrate Basic Genetic Concepts

1. Genetics: It’s in your BloodHemoglobin Workspace to Illustrate Basic Genetic Concepts Alix Darden, Dave Westenberg, Michael Rubin and Patty Shields

2. Audience • Genetics class • Majors and non majors

3. Major Objectives • To provide a framework for learning basic genetic principles • To use hemoglobinopathies to illustrate bioinformatics • To use primary literature in the classroom

4. Thalassemia • mutations in -globin lead to - thalassemia; mutations and deletions in -globin lead to - thalassemia • mutations in coding and non-coding regions • mutations found most frequently in people of Italian, Greek, Middle Eastern, Southern Asian and African ancestry • signs and symptoms • anemia (mild to severe) • untreated leads to severe complications • major cause cause of death - heart failure or infection

5. www.thalassemia.org

6. www.thalassemia.com Thematic AreasMendelian Inheritance • Pedigree analysis

7. Thematic AreasGene Expression • Mutation • Regulation of transcription • development regulation • Gene Structure and Splicing • Protein Structure

8. www.thalassemia.com Developmental expression Protein structure fig.cox.miami.edu/~cmallery/

9. Thematic AreasPopulation Genetics • Allelic Variation • Phylogenetics • Evolutionary Conservation

11. Defining the Problem Space • Background on Thalassemia • Thalassemia.com; thalassemia.org • PNAS paper (and other primary literature) • Data Set • DNA sequences • protein sequences • Links to tools • Biology Workbench, NBCI, JGI, Globin Gene Server, • References

12. Data Set PNAS (1994)91:1805-1809

15. 17 noncoding

16. 17 noncoding

17. 7 coding

18. 7 coding

19. gi_432460_gb_L26469.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATTTTTTTTCTTTTC gi_432461_gb_L26470.1_HUMBET TGTATGTGTGTACATATACACATATATATATATA--TTTTTTTTCTTTTC gi_432458_gb_L26467.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432455_gb_L26464.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432456_gb_L26465.1_HUMBET TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432454_gb_L26463.1_HUMBET TGTATGTGTGTACATATACACATATATATATATATTT--TTTTTCTTTTC gi_432457_gb_L26466.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432459_gb_L26468.1_HUMBET TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432462_gb_L26471.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTTCTTTTC gi_432463_gb_L26472.1_HUMBE TGTATGTGTGTATATATACACATATATATATATATATA--TTTTTTTTTC gi_432469_gb_L26478.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432467_gb_L26476.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432468_gb_L26477.1_HUMBE TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432466_gb_L26475.1_HUMBE TGTATGTGTGTATATATACACACATATATATATATAT--TTTTTCTTTTC gi_432464_gb_L26473.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTTCTTTTC gi_432465_gb_L26474.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTT-TTTTC gi_432453_gb_L26462.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC ******************************************

20. Potential Posed Problems • Ethnicity and allelic variation • Structure and function variation • gene • protein • Physiology of disease • Natural selection`