Doug Brutlag 2011 Diseases and Disease Databases Doug Brutlag Departments of Biochemistry & Medicine Stanford University School of Medicine

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 years until death

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 years until death Neurodegenerative disease –Loss of movement control –Loss of cognitive skills (dementia) and hallucinations –Depression, hostility, aggression and loss of inhibitions

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 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

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?

Doug Brutlag 2011 Genetic Penetrance

Doug Brutlag 2011 NCBI: National Center for Biotechnology Information

Doug Brutlag 2011 Genes and Disease 3/ 3/

Doug Brutlag 2011 Genes and Disease

Doug Brutlag 2011 Huntington Disease

Doug Brutlag 2011 Huntington Disease Genome View

Doug Brutlag 2011 Huntington Disease Gene

Doug Brutlag 2011 Huntington Disease Gene

Doug Brutlag 2011 MapViewer for Huntington

Doug Brutlag 2011 Huntingtin Protein

Doug Brutlag 2011 Huntingtin Protein

Doug Brutlag 2011 Huntington Disease Biosystem

Doug Brutlag 2011 Huntington Disease Gene Review

Doug Brutlag 2011 GeneTests & GeneReviews for Huntingtons

Doug Brutlag 2011 GeneTests for Huntington Disease Disease

Doug Brutlag 2011 GeneTests & GeneReviews

Doug Brutlag 2011 OMIM for Huntington Disease

Doug Brutlag 2011 OMIM Home Page

Doug Brutlag 2011 OMIM Home Page

Doug Brutlag 2011 OMIM Coverage % Genes > 33% Phenotypes > September 29, 2011

Doug Brutlag 2011 Huntington Disease Search in OMIM

Doug Brutlag 2011 Huntington Disease Entry in OMIM

Doug Brutlag 2011 Human Gene Mutation Database

Doug Brutlag 2011 Human Gene Mutation Database

Doug Brutlag 2011 Huntington Disease Entry in OMIM

Doug Brutlag 2011 Entrez Gene for Huntington ame=omim_gene&IdsFromResult= ame=omim_gene&IdsFromResult=143100

Doug Brutlag 2011 Genetics Home Reference

Doug Brutlag 2011 Genetics Home Reference for Huntington Disease

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

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

Doug Brutlag 2011 Age of Onset and Repeat Length

Doug Brutlag 2011 SNP Viewer for Huntington

Doug Brutlag 2011 HGMD for Huntington

Doug Brutlag 2011 Human Genome Nomenclature For Huntington

Doug Brutlag 2011 Cystic Fibrosis

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.

Doug Brutlag 2011 Cystic Fibrosis Transmembrane Conductance Regulator

Doug Brutlag 2011 Mutations Causing Cystic Fibrosis

Doug Brutlag 2011 Colorblindness in OMIM

Doug Brutlag 2011 Colorblindness in OMIM

Doug Brutlag 2011 Opsin1 Gene in OMIM

Doug Brutlag 2011 Opsin1MW Gene Entry

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?