Download Diseases and Disease Databases

Diseases and Disease Databases
http://biochem158.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
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NCBI: National Center for Biotechnology Information
http://www.ncbi.nlm.nih.gov/
Doug Brutlag 2011
Genes and
Diseasehttp://www.ncbi.nlm.nih.gov/books/NBK2218
3/
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Genes and Disease
http://www.ncbi.nlm.nih.gov/books/NBK22183/
Doug Brutlag 2011
Huntington Disease
http://www.ncbi.nlm.nih.gov/books/NBK22226/
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=
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
MapViewer for Huntington
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Huntingtin Protein
http://www.ncbi.nlm.nih.gov/protein/NP_002102.4
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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
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Huntington Disease Gene Review
http://www.ncbi.nlm.nih.gov/books/NBK1305/
Doug Brutlag 2011
GeneTests & GeneReviews for Huntingtons
http://www.ncbi.nlm.nih.gov/sites/GeneTests/
Doug Brutlag 2011
GeneTests for Huntington
Diseasehttp://www.ncbi.nlm.nih.gov/sites/GeneTests/
Doug Brutlag 2011
GeneTests & GeneReviews
http://www.ncbi.nlm.nih.gov/sites/GeneTests/
Doug Brutlag 2011
OMIM for Huntington Disease
http://www.ncbi.nlm.nih.gov/sites/GeneTests/
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OMIM Home Page
http://www.ncbi.nlm.nih.gov/omim
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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
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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&DbFrom=omim&Cmd=Link&LinkN
ame=omim_gene&IdsFromResult=143100
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Genetics Home Reference
http://ghr.nlm.nih.gov/
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Genetics Home Reference for Huntington Disease
http://ghr.nlm.nih.gov/condition/huntington-disease
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Predictive Testing for Huntington’s:
Adverse Psychological Events
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Huntington Disease can Arise from
Unequal Crossing Over During Meiosis
•
Crossing over between maternal and paternal chromosomes
Maternal
Paternal
Offspring
Offspring
•
Unequal crossing over between maternal and paternal chromosomes
Maternal
Paternal
Offspring
Offspring
Doug Brutlag 2011
Age of Onset and Repeat Length
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SNP Viewer for Huntington
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=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 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.
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Cystic Fibrosis Transmembrane
Conductance Regulator
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Mutations Causing Cystic Fibrosis
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Colorblindness in OMIM
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Colorblindness in OMIM
http://omim.org/entry/303800
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Opsin1 Gene in OMIM
http://omim.org/entry/300821
Doug Brutlag 2011
Opsin1MW Gene Entry
http://www.ncbi.nlm.nih.gov/gene/2652
Doug Brutlag 2011
Portrait of a Glitch
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•
•
•
•
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