1. Doug Brutlag 2011 Diseases and Disease Databases http://biochem158.stanford.edu/ http://biochem158.stanford.edu/ Doug Brutlag Departments of Biochemistry & Medicine Stanford University School of Medicine

2. Doug Brutlag 2011 Huntington Disease Autosomal Dominant –On the tip of the short arm of chromosome 4 –One bad gene causes disease (dominant) –Brain degeneration over 10-15 years until death

3. Doug Brutlag 2011 Huntington Disease Autosomal Dominant –On the tip of the short arm of chromosome 4 –One bad gene causes disease (dominant) –Brain degeneration over 10-15 years until death Neurodegenerative disease –Loss of movement control –Loss of cognitive skills (dementia) and hallucinations –Depression, hostility, aggression and loss of inhibitions

4. Doug Brutlag 2011 Huntington Disease Autosomal Dominant –On the tip of the short arm of chromosome 4 –One bad gene causes disease (dominant) –Brain degeneration over 10-15 years until death Neurodegenerative disease –Loss of movement control –Loss of cognitive skills (dementia) and hallucinations –Depression, hostility, aggression and loss of inhibitions Dyskinesias –Chorea: uncontrollable tics and involuntary movements of extremities, hyperkinesias –Dystonia uncontrollable muscle contractions –Dysphagia (difficulty in swallowing) and uncontrollable oral buccal dyskinesia –Bradykinesia, slow uncertain movements

5. Doug Brutlag 2011 The Inheritance You are 20 years old. Your father abandoned you and your mother when you only 2 years old. Your father died this year and left you an inheritance. He died from an autosomal dominant disease known as Huntington’s Chorea or Huntington’s Disease. You have a 50% chance of inheriting this invariably fatal neurodegenerative disease. But there is a genetic test for this disease that can tell you not only if you have the disease, and if you do, when you will die from it. Would you take the genetic test or not? Why?

6. Doug Brutlag 2011 Genetic Penetrance

7. Doug Brutlag 2011 NCBI: National Center for Biotechnology Information http://www.ncbi.nlm.nih.gov/ http://www.ncbi.nlm.nih.gov/

8. Doug Brutlag 2011 Genes and Disease http://www.ncbi.nlm.nih.gov/books/NBK2218 3/ http://www.ncbi.nlm.nih.gov/books/NBK2218 3/

9. Doug Brutlag 2011 Genes and Disease http://www.ncbi.nlm.nih.gov/books/NBK22183/ http://www.ncbi.nlm.nih.gov/books/NBK22183/

10. Doug Brutlag 2011 Huntington Disease http://www.ncbi.nlm.nih.gov/books/NBK22226/ http://www.ncbi.nlm.nih.gov/books/NBK22226/

11. Doug Brutlag 2011 Huntington Disease Genome View http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606&query=Huntington+AND+gene%5Bobj_type%5D&qchr= http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606&query=Huntington+AND+gene%5Bobj_type%5D&qchr=

12. Doug Brutlag 2011 Huntington Disease Gene http://www.ncbi.nlm.nih.gov/gene/3064 http://www.ncbi.nlm.nih.gov/gene/3064

13. Doug Brutlag 2011 Huntington Disease Gene http://www.ncbi.nlm.nih.gov/gene/3064 http://www.ncbi.nlm.nih.gov/gene/3064

14. Doug Brutlag 2011 MapViewer for Huntington

15. Doug Brutlag 2011 Huntingtin Protein http://www.ncbi.nlm.nih.gov/protein/NP_002102.4 http://www.ncbi.nlm.nih.gov/protein/NP_002102.4

16. Doug Brutlag 2011 Huntingtin Protein http://www.ncbi.nlm.nih.gov/protein/NP_002102.4 http://www.ncbi.nlm.nih.gov/protein/NP_002102.4

17. Doug Brutlag 2011 Huntington Disease Biosystem http://www.ncbi.nlm.nih.gov/gene/3064 http://www.ncbi.nlm.nih.gov/gene/3064

18. Doug Brutlag 2011 Huntington Disease Gene Review http://www.ncbi.nlm.nih.gov/books/NBK1305/ http://www.ncbi.nlm.nih.gov/books/NBK1305/

19. Doug Brutlag 2011 GeneTests & GeneReviews for Huntingtons http://www.ncbi.nlm.nih.gov/sites/GeneTests/ http://www.ncbi.nlm.nih.gov/sites/GeneTests/

20. Doug Brutlag 2011 GeneTests for Huntington Disease http://www.ncbi.nlm.nih.gov/sites/GeneTests/ Disease http://www.ncbi.nlm.nih.gov/sites/GeneTests/

21. Doug Brutlag 2011 GeneTests & GeneReviews http://www.ncbi.nlm.nih.gov/sites/GeneTests/ http://www.ncbi.nlm.nih.gov/sites/GeneTests/

22. Doug Brutlag 2011 OMIM for Huntington Disease http://www.ncbi.nlm.nih.gov/sites/GeneTests/ http://www.ncbi.nlm.nih.gov/sites/GeneTests/

23. Doug Brutlag 2011 OMIM Home Page http://www.ncbi.nlm.nih.gov/omim http://www.ncbi.nlm.nih.gov/omim

24. Doug Brutlag 2011 OMIM Home Page http://omim.org/ http://omim.org/

25. Doug Brutlag 2011 OMIM Coverage http://www.ncbi.nlm.nih.gov/Omim/mimstats.html http://www.ncbi.nlm.nih.gov/Omim/mimstats.html 67 % Genes > 33% Phenotypes > September 29, 2011

26. Doug Brutlag 2011 Huntington Disease Search in OMIM http://www.ncbi.nlm.nih.gov/omim http://www.ncbi.nlm.nih.gov/omim

27. Doug Brutlag 2011 Huntington Disease Entry in OMIM http://www.ncbi.nlm.nih.gov/omim/143100 http://www.ncbi.nlm.nih.gov/omim/143100

28. Doug Brutlag 2011 Human Gene Mutation Database http://www.hgmd.cf.ac.uk/ac/ http://www.hgmd.cf.ac.uk/ac/

29. Doug Brutlag 2011 Human Gene Mutation Database http://www.hgmd.cf.ac.uk/ac/ http://www.hgmd.cf.ac.uk/ac/

30. Doug Brutlag 2011 Huntington Disease Entry in OMIM http://www.ncbi.nlm.nih.gov/omim/143100 http://www.ncbi.nlm.nih.gov/omim/143100

31. Doug Brutlag 2011 Entrez Gene for Huntington http://www.ncbi.nlm.nih.gov/sites/entrez?itool=omim_Detailed&DbFrom=omim&Cmd=Link&LinkN ame=omim_gene&IdsFromResult=143100 http://www.ncbi.nlm.nih.gov/sites/entrez?itool=omim_Detailed&DbFrom=omim&Cmd=Link&LinkN ame=omim_gene&IdsFromResult=143100

32. Doug Brutlag 2011 Genetics Home Reference http://ghr.nlm.nih.gov/ http://ghr.nlm.nih.gov/

33. Doug Brutlag 2011 Genetics Home Reference for Huntington Disease http://ghr.nlm.nih.gov/condition/huntington-disease http://ghr.nlm.nih.gov/condition/huntington-disease

34. Doug Brutlag 2011 Predictive Testing for Huntington’s: Adverse Psychological Events

35. Doug Brutlag 2011 Crossing over between maternal and paternal chromosomes Unequal crossing over between maternal and paternal chromosomes Huntington Disease can Arise from Unequal Crossing Over During Meiosis Maternal Paternal Offspring

36. Doug Brutlag 2011 Age of Onset and Repeat Length

37. Doug Brutlag 2011 SNP Viewer for Huntington http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=3064 http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=3064

38. Doug Brutlag 2011 HGMD for Huntington http://www.hgmd.cf.ac.uk/ac/gene.php?gene=HD http://www.hgmd.cf.ac.uk/ac/gene.php?gene=HD

39. Doug Brutlag 2011 Human Genome Nomenclature For Huntington http://www.genenames.org/data/hgnc_data.php?hgnc_id=4851 http://www.genenames.org/data/hgnc_data.php?hgnc_id=4851

40. Doug Brutlag 2011 Cystic Fibrosis

41. Doug Brutlag 2011 Cystic Fibrosis Autosomal (chromosome 7q31.2) recessive. Inhibits many bodily secretions –Pancreatic digestive enzymes –Sweat glands –Lung mucosa in alveoli and bronchi –Infertility in males (>97%) –Cirrhosis of the liver –Hepatic steatosis Caused by mutations in the CFTR gene that encodes a chloride ion channel that pumps Chloride ion and water out of cells.

42. Doug Brutlag 2011 Cystic Fibrosis Transmembrane Conductance Regulator

43. Doug Brutlag 2011 Mutations Causing Cystic Fibrosis

44. Doug Brutlag 2011 Colorblindness in OMIM

45. Doug Brutlag 2011 Colorblindness in OMIM http://omim.org/entry/303800 http://omim.org/entry/303800

46. Doug Brutlag 2011 Opsin1 Gene in OMIM http://omim.org/entry/300821 http://omim.org/entry/300821

47. Doug Brutlag 2011 Opsin1MW Gene Entry http://www.ncbi.nlm.nih.gov/gene/2652 http://www.ncbi.nlm.nih.gov/gene/2652

48. Doug Brutlag 2011 Portrait of a Glitch Revere La Noue, MFA, Stanford, 2005 What is this film about? What classes of glitches are mentioned? What do these glitches cause? Why did I show this film?