SNP Resources Finding SNPs Databases and Data Extraction

SNP Resources: Finding SNPs, Databases and Data Extraction Debbie Nickerson NIEHS SNPs Workshop

Genotype - Phenotype Studies You have candidate gene/region/pathway of interest and samples ready to study: What SNPs are available? How do I find the common SNPs? What is the validation/quality of the SNPs? Are these SNPs informative in my population/samples? What can I download information? How do I pick the “best” SNPs? - Dana Crawford

Minimal SNP information for genotyping/characterization • What is the SNP? Flanking sequence and alleles. ü FASTA format >snp_name ACCGAGTAGCCAG [A/G] ACTGGGATAGAAC • • db. SNP reference SNP # (rs #) Where is the SNP mapped? Exon, promoter, UTR, etc 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 (>5%), rare Are other SNPs associated - redundant? Is genotyping data for control populations available?

Finding SNPs: Databases and Extraction How do I find and download SNP data for analysis/genotyping? 1. NIEHS Environmental Genome Project (EGP) Candidate gene website 2. NIEHS web applications and other tools Gene. SNPS, Poly. Doms, Poly. Phen, GVS 3. Hap. Map Genome Browser 4. Entrez Gene - db. SNP - Entrez SNP

Finding SNPs: NIEHS SNPs Candidate Genes egp. gs. washington. edu

Finding SNPs: NIEHS SNPs Candidate Genes

African American African YRI European CEU Hispanic Asian CHB JPT

SNP_pos <tab> Ind_ID <tab> allele 1 <tab> allele 2 Repeat for all individuals Repeat for next SNP

Poly. Phen - Polymorphism Phenotyping Structural protein characteristics and evolutionary comparison SIFT = Sorting Intolerant From Tolerant Evolutionary comparison of non-synonymous SNPs

Finding SNPs: NIEHS SNPs Candidate Genes

Finding SNPs: NIEHS SNPs Candidate Genes egp. gs. washington. edu

Finding SNPs: NIEHS SNPs Candidate Genes

Finding SNPs: Databases and Extraction How do I find and download SNP data for analysis/genotyping? 1. NIEHS Environmental Genome Project (EGP) Candidate gene website 2. NIEHS web applications and other tools Gene. SNPS, Poly. Doms, Poly. Phen, GVS 3. Hap. Map Genome Browser 4. Entrez Gene - db. SNP - Entrez SNP

Gene. SNPs http: //www. genome. utah. edu/genesnps/ Graphic view of SNPs in context of gene elements All NIEHS genes presented - organized by pathway/function SNPs from db. SNP - organized by submitter handle Link-outs to Entrez. SNP pages and other resources Multiple views of SNPs in contexts of gene elements, protein domains, linkage disequilibrium Tutorial available from Open. Helix (http: //www. openhelix. com)

Gene SNPs - http: //www. genome. utah. edu/genesnps/

Gene. SNPs navigation

Gene. SNPs links to other resouces

Gene. SNPs: multiple views of SNPS in context of gene elements

Polydoms A web-based application that maps synonymous and non-synonymous SNPs onto known functional protein domains • • SNPs are from db. SNP and Gene. SNPs Domain structures from NCBI's Conserved Domain Database Functional predictions based on SIFT and Poly. Phen 3 dimensional mapping of SNPs on protein structure using Chime viewer http: //polydoms. cchmc. org/polydoms/

Polydoms - http: //polydoms. cchmc. org/polydoms/

Polydoms - http: //polydoms. cchmc. org/polydoms/ Scroll Down

Poly. Phen: Polymorphism Phenotypingprediction of functional effect of human ns. SNPs Physical and comparative analyses used to make predictions Uses Swiss. Prot 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: //genetics. bwh. harvard. edu/pph/

Poly. Phen: Polymorphism Phenotypingprediction of functional effect of human ns. SNPs

GVS: Genome Variation Server http: //gvs. gs. washington. edu/GVS/ Provides rapid analysis of 4. 5 million genotyped SNPs from db. SNP and the Hap. Mapped to human genome build 36 (hg 18) Displays genotype data in text and image formats Displays tag. SNPs or clusters of informative SNPs in text and image formats Displays linkage disequilibrium (LD) in text and image formats Online tutorial provided at Open. Helix. com

GVS: Genome Variation Server ADH 4 http: //gvs. gs. washington. edu/GVS/

GVS: Genome Variation Server

GVS: Genome Variation Server • Table of genotypes • Image of visual genotypes

GVS: Genome Variation Server Genotypes displayed in prettybase table and visual genotype graphic

GVS: Genome Variation Server

GVS: Genome Variation Server Dense genotypes around a candidate gene can be integrated with broader Hap. Map genotypes High Density Genic Coverage (EGP) Low Density Genome Coverage (Hap. Map) = EGP SNP discovery (1/200 bp) = Hap. Map SNPs (~1/1000 bp)

GVS: Genome Variation Server Dense genotypes around a candidate gene can be integrated with lower-density Hap. Map genotypes

GVS: Genome Variation Server A. Common samplescombined variations B. B. Combined samplescommon variations C. Combined samplescombined variations Common Combined

GVS: Genome Variation Server -Common samples- A. Common samplescombined variations Combined variations

GVS: Genome Variation Server Hap. Map -Combined samples- EGP B. Combined samplescommon variations

GVS: Genome Variation Server C. Combined samplescombined variations -Combined samples- Combined variations

Finding SNPs: Databases and Extraction How do I find and download SNP data for analysis/genotyping? 1. NIEHS Environmental Genome Project (EGP) Candidate gene website 2. NIEHS web applications and other tools Gene. SNPS, Poly. Doms, Poly. Phen, GVS 3. Hap. Map Genome Browser 4. Entrez Gene - db. SNP - Entrez SNP

www. hapmap. org

Finding SNPs: Hap. Map Browser

Finding SNPs: Hap. Map Genotypes

Finding SNPs: Hap. Map Browser 1. Hap. Map data sets are useful because individual genotype data in deeply sampled populations can be used to determine optimal genotyping strategies (tag. SNPs) or perform population genetic analyses (linkage disequilbrium) 2. Data are specific to the Hap. Map project (not all db. SNP) ü Hap. Map data is available in db. SNP 3. Visualization of data and direct access to SNP data, individual genotypes, and LD analysis possible in the browser and formats can be saved for Haploview

Finding SNPs: Databases and Extraction How do I find and download SNP data for analysis/genotyping? 1. NIEHS Environmental Genome Project (EGP) Candidate gene website 2. NIEHS web applications and other tools Gene. SNPS, Poly. Doms, Poly. Phen, GVS 3. Hap. Map Genome Browser 4. Entrez Gene - db. SNP - Entrez SNP

NCBI - Database Resource NOS 2 A www. ncbi. nlm. nih. gov

Finding SNPs using NCBI databases http: //www. ncbi. nlm. nih. gov/

Default View c. SNPs

Finding SNPs using NCBI databases http: //www. ncbi. nlm. nih. gov/

Entrez SNP - Query Term Capabilities

Finding SNPs - Entrez SNP Summary 1. db. SNP is useful for investigating detailed information on a small number SNPs - and it’s good for a picture of the gene 2. Entrez SNP is a direct, fast database for querying SNP data 3. Data from Entrez SNP can be retrieved in batches for many SNPs 4. Entrez SNP data can be “limited” to specific subsets of SNPs and formatted in plain text for easy parsing and manipulation 5. More detailed queries can be formed using specific “field tags” for retrieving SNP data

Summary Finding SNPs: Databases and Extraction Reviewing candidate genes using views and resources in - NIEHS SNPs - Gene. SNPs Prediction of functional variations - Polydoms and Poly. Phen Integration of dense, gene-centric SNP maps with genomic Hap. Map SNPs - GVS Hap. Map viewer NCBI databases through Entrez portal -Entrez Gene, db. SNP, Entrez SNP -many ways to retrieve and format data