Diseases and Disease Databases http biochem 158 stanford
Diseases and Disease Databases http: //biochem 158. stanford. edu/ 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 10 -15 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 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 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 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 http: //www. ncbi. nlm. nih. gov/ Doug Brutlag 2011
Genes and Diseasehttp: //www. ncbi. nlm. nih. gov/books/NBK 2218 3/ Doug Brutlag 2011
Genes and Disease http: //www. ncbi. nlm. nih. gov/books/NBK 22183/ Doug Brutlag 2011
Huntington Disease http: //www. ncbi. nlm. nih. gov/books/NBK 22226/ Doug Brutlag 2011
Huntington Disease Genome View http: //www. ncbi. nlm. nih. gov/projects/mapview/map_search. cgi? taxid=9606&query=Huntington+AND+gene%5 Bobj_type%5 D&qchr= Doug Brutlag 2011
Huntington Disease Gene http: //www. ncbi. nlm. nih. gov/gene/3064 Doug Brutlag 2011
Huntington Disease Gene http: //www. ncbi. nlm. nih. gov/gene/3064 Doug Brutlag 2011
Map. Viewer for Huntington Doug Brutlag 2011
Huntingtin Protein http: //www. ncbi. nlm. nih. gov/protein/NP_002102. 4 Doug Brutlag 2011
Huntingtin Protein http: //www. ncbi. nlm. nih. gov/protein/NP_002102. 4 Doug Brutlag 2011
Huntington Disease Biosystem http: //www. ncbi. nlm. nih. gov/gene/3064 Doug Brutlag 2011
Huntington Disease Gene Review http: //www. ncbi. nlm. nih. gov/books/NBK 1305/ Doug Brutlag 2011
Gene. Tests & Gene. Reviews for Huntingtons http: //www. ncbi. nlm. nih. gov/sites/Gene. Tests/ Doug Brutlag 2011
Gene. Tests for Huntington Diseasehttp: //www. ncbi. nlm. nih. gov/sites/Gene. Tests/ Doug Brutlag 2011
Gene. Tests & Gene. Reviews http: //www. ncbi. nlm. nih. gov/sites/Gene. Tests/ Doug Brutlag 2011
OMIM for Huntington Disease http: //www. ncbi. nlm. nih. gov/sites/Gene. Tests/ Doug Brutlag 2011
OMIM Home Page http: //www. ncbi. nlm. nih. gov/omim Doug Brutlag 2011
OMIM Home Page http: //omim. org/ Doug Brutlag 2011
OMIM Coverage http: //www. ncbi. nlm. nih. gov/Omim/mimstats. html September 29, 2011 > > 67% Genes 33% Phenotypes Doug Brutlag 2011
Huntington Disease Search in OMIM http: //www. ncbi. nlm. nih. gov/omim Doug Brutlag 2011
Huntington Disease Entry in OMIM http: //www. ncbi. nlm. nih. gov/omim/143100 Doug Brutlag 2011
Human Gene Mutation Database http: //www. hgmd. cf. ac. uk/ac/ Doug Brutlag 2011
Human Gene Mutation Database http: //www. hgmd. cf. ac. uk/ac/ Doug Brutlag 2011
Huntington Disease Entry in OMIM http: //www. ncbi. nlm. nih. gov/omim/143100 Doug Brutlag 2011
Entrez Gene for Huntington http: //www. ncbi. nlm. nih. gov/sites/entrez? itool=omim_Detailed&Db. From=omim&Cmd=Link&Link. N ame=omim_gene&Ids. From. Result=143100 Doug Brutlag 2011
Genetics Home Reference http: //ghr. nlm. nih. gov/ Doug Brutlag 2011
Genetics Home Reference for Huntington Disease http: //ghr. nlm. nih. gov/condition/huntington-disease Doug Brutlag 2011
Predictive Testing for Huntington’s: Adverse Psychological Events Doug Brutlag 2011
Huntington Disease can Arise from Unequal Crossing Over During Meiosis • Crossing over between maternal and paternal chromosomes Maternal Paternal Offspring • Unequal crossing over between maternal and paternal chromosomes Maternal Paternal Offspring Doug Brutlag 2011
Age of Onset and Repeat Length Doug Brutlag 2011
SNP Viewer for Huntington http: //www. ncbi. nlm. nih. gov/SNP/snp_ref. cgi? locus. Id=3064 Doug Brutlag 2011
HGMD for Huntington http: //www. hgmd. cf. ac. uk/ac/gene. php? gene=HD Doug Brutlag 2011
Human Genome Nomenclature For Huntington http: //www. genenames. org/data/hgnc_data. php? hgnc_id=4851 Doug Brutlag 2011
Cystic Fibrosis Doug Brutlag 2011
Cystic Fibrosis • Autosomal (chromosome 7 q 31. 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 http: //omim. org/entry/303800 Doug Brutlag 2011
Opsin 1 Gene in OMIM http: //omim. org/entry/300821 Doug Brutlag 2011
Opsin 1 MW Gene Entry http: //www. ncbi. nlm. nih. gov/gene/2652 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? Doug Brutlag 2011
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