ALU Polymorphisms Unit QuestionsALU Polymorphisms Unit Questions

1.What does DNA tell us about ourselves?

2.In what ways can DNA be altered and what effects can alterations have?

3. What gear and skills are needed to study DNA?

Co-authored by…Co-authored by…

• Chris Munzert – Mt. Hope

• Marcia King – Mt. Hope

• Janet Butler – Davies Career and Tech.

• John Wemple – Providence Schools

• Chris Moon – Providence Schools

PART I: Neurofibamatosis: A PART I: Neurofibamatosis: A human genetic disorder caused by human genetic disorder caused by a mutation in the Neurofibromin a mutation in the Neurofibromin Gene (NF-1)Gene (NF-1)

PART II: Alu Insertion LabPART II: Alu Insertion Lab

OPTIONAL GUEST SPEAKER OPTIONAL GUEST SPEAKER DAY – Career ConnectionDAY – Career Connection

• Genetic Counselor

WHAT IS RESPONSIBLE FOR WHAT IS RESPONSIBLE FOR THE SYMPTOMS JUST THE SYMPTOMS JUST

OBSERVED?OBSERVED?

• Genetic Disorders

Neurofibromatosis InformationNeurofibromatosis InformationSouce:http://www.emedicine.com/derm/topic287.htmSouce:http://www.emedicine.com/derm/topic287.htm

• Background: Neurofibromatosis is an autosomal dominant disorder that affects the bone, the nervous system, soft tissue, and the skin.

• Race: All racial groups are affected equally.

• Sex: Women and men are affected equally by neurofibromatosis.

• Frequency: Worldwide, NF-1 occurs in approximately 1 of 2500-3300 live births.

• Mortality: Patients with NF-1 have an estimated 3-15% additional risk of malignant disease in their lifetime. (The mortality rate is higher than that of the healthy population because of the increased potential for malignant transformation of diseased tissues and the development of neurofibrosarcoma.)

Meet Joseph Merrick – For a long time, it was thought that he had neurofibromatosis

Class Articles: Pair ShareClass Articles: Pair Share

• Joseph Merrick: “The Elephant Man”– Article #1: History of Joseph Merrick

• http://myhomeoflove.tripod.com/shortstories/merrick.html

– Article #2: A comparative analysis of “Elephant Man’s Disease”

• http://www.dartmouth.edu/~dujs/1999S/03_Merrick.pdf

• Living with Neurofibromatosis: Real people, real stories…

DAY 2DAY 2Assessing Prior KnowledgeAssessing Prior Knowledge

• DNA RNA Protein – Overview Animations– Details on Transcription - Animation– Details on Translation - Animation

DAY 3DAY 3What does the normal NF-1 gene What does the normal NF-1 gene

do?do?• Animation of NF-1 Gene comparing norma

l function with mutated functions.

• Rotate a 3-D model of the NF-1 protein

DAY 4DAY 4How do the versions of the genes differ?How do the versions of the genes differ? Sequence Alignment ActivitySequence Alignment Activity

• Normal DNA Sequence vs. Mutant DNA Sequence

• LALIGN – Genomic DNA

• Teacher Comment: Details on Mutation: Alu element inserts into an intron; this changes the splicing pattern that ultimately results in the deletion of exon #6.

DAY 5DAY 5PRE-LAB NOTESPRE-LAB NOTES

• Mutation Refresher Activity– Deletions– Insertions– Duplications– Etc…

DAY 6DAY 6What caused the NF-1 mutation?What caused the NF-1 mutation?

• Meet Alu…

• A de novo Alu insertion results in neurofibromatosis type 1 Nature 353, 864 - 866 (31 October 1991); doi:10.1038/353864a0

• What other diseases are caused by Alu insertions?

Source DocumentSource Documenthttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNG-45FSDCM-http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNG-45FSDCM-

25&_user=489286&_coverDate=07%2F31%2F1999&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000022678&_version=1&_urlVersion=0&_user25&_user=489286&_coverDate=07%2F31%2F1999&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000022678&_version=1&_urlVersion=0&_userid=489286&md5=1c3c2d942c3aae40e11b4ceddb92223fid=489286&md5=1c3c2d942c3aae40e11b4ceddb92223f

Why should I Why should I notnot think Alu think Alu is only associated with is only associated with

disease?disease?• The vast majority of “Alus” are located in The vast majority of “Alus” are located in

intronsintrons, where they appear to have no , where they appear to have no phenotypic effect… phenotypic effect…

• Alu insertions in the primate genome have Alu insertions in the primate genome have been occurring for millions of years…been occurring for millions of years…

• Alu insertions have been used to study Alu insertions have been used to study patterns of human migration.patterns of human migration.

• Follow this link to an interesting animation of human migration

DAYS 7DAYS 7Alu Insertion LabAlu Insertion Lab

• DAY 7– Extract DNA and freeze

• DAY 8– Setup PCR– Flex Time

• Teacher Note: Drop off PCR samples today to Megan.

• DAY 9– Guest Speaker: Applying Bioinformatics to answer

real questions

LAB Continues…LAB Continues…

• DAY 10– Electrophoresis and Photography– Possible Results and Explanations

• HW: Alu within an Alu gel anomaly

• DAY 11– Discuss Homework: Alu within an Alu gel anomaly– Analyze Gels

• Expected movement of the bands• What does it mean if they have at least one Alu-element?• Utility of Alu Insertion information in Evolution Studies

• DAY 12– PANEL DISCUSSION: Kary Mullis and Craig Venter and

Francis Collins