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

Audience Genetics class Majors and non majors

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

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

Thematic Areas Mendelian Inheritance Pedigree analysis

Thematic Areas Gene Expression Mutation Regulation of transcription  development regulation Gene Structure and Splicing Protein Structure

fig.cox.miami.edu/~cmallery/ Developmental expression Protein structure

Thematic Areas Population Genetics Allelic Variation Phylogenetics Evolutionary Conservation

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

Data Set PNAS (1994)91:

17 noncoding

7 coding

gi_432460_gb_L _HUMBE TGTATGTGTGTACATATACACATATATATATATATATTTTTTTTCTTTTC gi_432461_gb_L _HUMBET TGTATGTGTGTACATATACACATATATATATATA--TTTTTTTTCTTTTC gi_432458_gb_L _HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432455_gb_L _HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432456_gb_L _HUMBET TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432454_gb_L _HUMBET TGTATGTGTGTACATATACACATATATATATATATTT--TTTTTCTTTTC gi_432457_gb_L _HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432459_gb_L _HUMBET TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC gi_432462_gb_L _HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTTCTTTTC gi_432463_gb_L _HUMBE TGTATGTGTGTATATATACACATATATATATATATATA--TTTTTTTTTC gi_432469_gb_L _HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432467_gb_L _HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432468_gb_L _HUMBE TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTC gi_432466_gb_L _HUMBE TGTATGTGTGTATATATACACACATATATATATATAT--TTTTTCTTTTC gi_432464_gb_L _HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTTCTTTTC gi_432465_gb_L _HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTT-TTTTC gi_432453_gb_L _HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC ************ ********* *********** * **** *****

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