SNP Resources: Finding SNPs

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SNP Resources Finding SNPs Databases and Data
Extraction
Mark J. Rieder, PhD SeattleSNPs Variation
Workshop March 20-21, 2006
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Genotype - Phenotype Studies
Typical Approach I have candidate gene/region
and samples ready to study. Tell me what SNPs
to genotype.
Other questions How do I know I have all the
SNPs? What is the validation/quality of the SNPs
that are known? Are these SNPs informative in my
population/sample? What do I need to know for
selecting the best SNPs? How do I pick the
best SNPs?
What information do I need to characterize a SNP
for genotyping?
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Minimal SNP information for genotyping/characteriz
ation

• What is the SNP? Flanking sequence and
  alleles.
• FASTA format
• gtsnp_name
• ACCGAGTAGCCAG
• A/G
• ACTGGGATAGAAC
• dbSNP reference SNP (rs )
• Where is the SNP mapped? Exon, promoter, UTR,
  etc
• picture of gene with mapped to the gene
  structure.
• How was it discovered? Method
• What assurances do you have that it is real?
  Validated how?
• What population African, European, etc?
• What is the allele frequency of each SNP?
  Common (gt10), rare
• Are other SNPs associated - redundant?
  Genotyping data!

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Finding SNPs Databases and Extraction
How do I find and download SNP data for
analysis/genotyping?
1. Entrez Gene - dbSNP - Entrez SNP 2. HapMap
Genome Browser 3. SeattleSNPs PGA Candidate
gene website 4. Web applications and other
tools NIEHS, PolyPhen, ECR Browser
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NCBI - Database Resource
IL1B
www.ncbi.nlm.nih.gov
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Finding SNPs Where do I start?
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Finding SNPs Where do I start?
NCBI - Entrez Gene (LocusLink replacement)
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Finding SNPs Entrez Gene
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dbSNP Geneview
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dbSNP Geneview
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Finding SNPs dbSNP validation
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Finding SNPs dbSNP database
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Entrez SNP - dbSNP genotype retrieval
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Finding SNPs - Gene Genotype Report
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Graphic display of genotype data - Visual Genotype
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Finding SNPs - Gene Genotype Report
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Finding SNPs - Gene Genotype Report
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Minimal SNP information for genotyping/characteriz
ation

• What is the SNP? Flanking sequence and
  alleles.
• FASTA format
• gtsnp_name
• ACCGAGTAGCCAG
• A/G
• ACTGGGATAGAAC
• dbSNP reference SNP (rs )
• Where is the SNP mapped? Exon, promoter, UTR,
  etc
• picture of gene with mapped to the gene
  structure.
• How was it discovered? Method
• What assurances do you have that it is real?
  Validated how?
• What population African, European, etc?
• What is the allele frequency of each SNP?
  Common (gt10), rare
• Are other SNPs associated - redundant?
  Genotyping data!

dbSNP - data is there
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Entrez Gene Entry - Entrez SNP
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Entrez SNP - direct dbSNP querying
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Entrez SNP - Parseable Multi-SNP reports
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Entrez SNP - Parseable Multi-SNP reports
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Entrez SNP - Search Limiting Capabilities
IL1B
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Entrez SNP - Search Limits
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Entrez SNP - Search Limiting Capabilities
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Entrez SNP - More Limit Searching
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Entrez SNP - More Limit Searching
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Entrez SNP - Query Term Capabilities
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Entrez SNP - Search Terms Fields
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Entrez SNP - Search Terms Fields
More advanced queries
2CHR AND "coding nonsynon"FUNC
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Entrez SNP - Search Terms Fields
More advanced queries
2CHR AND "coding nonsynonymous"FUNC AND
"PGA-UW-FHCRC"HANDLE Note Can also use
wildcard () characters, AND, OR, and NOT
operators
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Entrez SNP - Advanced Queries
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Minimal SNP information for genotyping/characteriz
ation

• What is the SNP? Flanking sequence and
  alleles.
• FASTA format
• gtsnp_name
• ACCGAGTAGCCAG
• A/G
• ACTGGGATAGAAC
• dbSNP reference SNP (rs )
• Where is the SNP mapped? Exon, promoter, UTR,
  etc
• picture of gene with mapped to the gene
  structure.
• How was it discovered? Method
• What assurances do you have that it is real?
  Validated how?
• What population African, European, etc?
• What is the allele frequency of each SNP?
  Common (gt10), rare
• Are other SNPs associated - redundant?
  Genotyping data!

EntrezSNP - better!
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Finding SNPs - Entrez SNP Summary

• dbSNP is useful for investigating detailed
  information on a
• small number SNPs - and its good for a picture of
  the gene
• Entrez SNP is a direct, fast, database for
  querying SNP data.
• Data from Entrez SNP can be retrieved in batches
  for many SNPs
• Entrez SNP data can be limited to specific
  subsets of SNPs
• and formatted in plain text for easy parsing and
  manipulation
• More detailed queries can be formed using
  specific field tags
• for retrieving SNP data

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Finding SNPs Databases and Extraction
How do I find and download SNP data for
analysis/genotyping?
1. Entrez Gene - dbSNP - Entrez SNP 2. HapMap
Genome Browser 3. SeattleSNPs PGA Candidate
gene website 4. Web applications and other
tools NIEHS, PolyPhen, ECR Browser
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www.hapmap.org
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Finding SNPs HapMap Browser
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Finding SNPs HapMap Browser
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Finding SNPs HapMap Genotypes
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Finding SNPs HapMap Browser
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Minimal SNP information for genotyping/characteriz
ation

• What is the SNP? Flanking sequence and
  alleles.
• FASTA format
• gtsnp_name
• ACCGAGTAGCCAG
• A/G
• ACTGGGATAGAAC
• dbSNP reference SNP (rs )
• Where is the SNP mapped? Exon, promoter, UTR,
  etc
• picture of gene with mapped to the gene
  structure.
• How was it discovered? Method
• What assurances do you have that it is real?
  Validated how?
• What population African, European, etc?
• What is the allele frequency of each SNP?
  Common (gt10), rare
• Are other SNPs associated - redundant?
  Genotyping data!

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Finding SNPs HapMap Browser

• HapMap data sets are useful because
• individual genotype data can be used to determine
  optimal
• genotyping strategies (tagSNPs) or perform
  population
• genetic analyses (linkage disequilbrium)
• Data are specific produced by those projects (not
  all dbSNP)
• HapMap data is available in dbSNP
• HapMap data (Phase II) can be accessed preleased
  prior to dbSNPs
• Easier visualization of data and direct access to
  
• SNP data, individual genotypes, and LD analysis

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Finding SNPs Databases and Extraction
How do I find and download SNP data for
analysis/genotyping?
1. Entrez Gene - dbSNP - Entrez SNP 2. HapMap
Genome Browser 3. SeattleSNPs PGA Candidate
gene website 4. Web applications and other
tools NIEHS, PolyPhen, ECR Browser
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Finding SNPs SeattleSNPs Candidate Genes
pga.gs.washington.edu
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Finding SNPs SeattleSNPs Candidate Genes
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Finding SNPs SeattleSNPs Candidate Genes
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HapMap Compatible
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Finding SNPs SeattleSNPs Candidate Genes
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Finding SNPs SeattleSNPs Candidate Genes
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SNP_pos lttabgt Ind_ID lttabgt allele1 lttabgt
allele2 Repeat for all individuals Repeat for
next SNP
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SIFT Sorting Intolerant From Tolerant Evolution
ary comparison of non-synonymous SNPs PolyPhen -
Polymorphism Phenotyping Structural protein
characteristics and evolutionary comparison
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PolyPhen Polymorphism Phenotyping- prediction
of functional effect of human nsSNPs
Physical and comparative analyses used to make
predictions Uses SwissProt annotations to
identify known domains Calculates a substitution
probability from BLAST alignments of homologous
and orthologous sequences Ranks substitutions on
scale of predicted functional effects from
benign to probably damaging
http//tux.embl-heidelberg.de/ramensky/
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PolyPhen Polymorphism Phenotyping- prediction
of functional effect of human nsSNPs
tux.embl-heidelberg.de/ramensky/
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Finding SNPs SeattleSNPs Candidate Genes
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Finding SNPs SeattleSNPs Candidate Genes
pga.gs.washington.edu
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Finding SNPs SeattleSNPs Candidate Genes
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Finding SNPs NIEHS SNPs Candidate Genes
egp.gs.washington.edu
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ECR Browser Evolutionary Conserved Regions
Aligns sequences to Mouse, Rat, Dog, Opposum,
Chicken, Fugu and Drosophila Gene annotations
from UCSC Genome Browser Easy retrieval of ECR
sequences and alignments Pre-computed
transcription factor binding sites
http//ecrbrowser.dcode.org
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ECR Browser Evolutionary Conserved Regions
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ECR Browser Evolutionary Conserved Regions
Human-mouse alignment
Fasta sequences
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ECR Browser Evolutionary Conserved Regions
Transcription Factor Binding Sites from Transfac
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Finding SNPs Databases and Extraction
Entrez SNP (www.ncbi.nlm.nih.gov/entrez) Direct
access to dbSNP data - versatile and flexible
querying HapMap Browser (hapmap.org) Access to
large scale genotype data Rapid/early access on
HapMap website Browsers provide visualization
and other analysis tools SeattleSNPs
(pga.gs.washington.edu) Candidate gene focused -
inflammation - HLBS phenotypes Comprehensive SNP
data from resequencing Early access - prior to
dbSNP release Other Resources NIEHS SNPS
(egp.gs.washington.edu), Polyphen, ECR (with
TransFac)