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

www.thalassemia.org

Thematic AreasMendelian Inheritance

• Pedigree analysis

www.thalassemia.com

Thematic AreasGene Expression

• Mutation• Regulation of transcription

development regulation

• Gene Structure and Splicing• Protein Structure

www.thalassemia.com

fig.cox.miami.edu/~cmallery/

Developmental expression

Protein structure

Thematic AreasPopulation 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)91:1805-1809

17 noncoding

17 noncoding

7 coding

7 coding

gi_432460_gb_L26469.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATTTTTTTTCTTTTCgi_432461_gb_L26470.1_HUMBET TGTATGTGTGTACATATACACATATATATATATA--TTTTTTTTCTTTTCgi_432458_gb_L26467.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTCgi_432455_gb_L26464.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTCgi_432456_gb_L26465.1_HUMBET TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTCgi_432454_gb_L26463.1_HUMBET TGTATGTGTGTACATATACACATATATATATATATTT--TTTTTCTTTTCgi_432457_gb_L26466.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTCgi_432459_gb_L26468.1_HUMBET TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTCgi_432462_gb_L26471.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTTCTTTTCgi_432463_gb_L26472.1_HUMBE TGTATGTGTGTATATATACACATATATATATATATATA--TTTTTTTTTCgi_432469_gb_L26478.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTCgi_432467_gb_L26476.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTCgi_432468_gb_L26477.1_HUMBE TGTATGTGTGTATATATACACATATATATATATATTT--TTTTTCTTTTCgi_432466_gb_L26475.1_HUMBE TGTATGTGTGTATATATACACACATATATATATATAT--TTTTTCTTTTCgi_432464_gb_L26473.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTTCTTTTCgi_432465_gb_L26474.1_HUMBET TGTATGTGTGTATATATACACATATATATATATATAT--TTTTT-TTTTCgi_432453_gb_L26462.1_HUMBE TGTATGTGTGTACATATACACATATATATATATATATATTTTTTCTTTTC ************ ********* *********** * **** *****

Potential Posed Problems

• Ethnicity and allelic variation• Structure and function

variation gene protein

• Physiology of disease• Natural selection`