A Tutorial Lincoln Stein, Cold Spring Harbor Laboratory Using HapMap.Org A Tutorial Lincoln Stein, Cold Spring Harbor Laboratory

Goal of This Tutorial This tutorial will show you how to: Find HapMap SNPs near a gene or region of interest (ROI). View patterns of LD in the ROI. Select tag SNPs in the ROI. Download information on the SNPs in ROI for use in Haploview. Generate customized extracts of the entire data set. Download the entire data set in bulk.

Finding HapMap SNPs in a Region of Interest Find the region of the genome containing the DTNBP1 gene. Identify the characterized SNPs in the region. View the patterns of LD in the region. Pick tag SNPs. Download the region in Haploview format.

1: Surf to the HapMap Browser 1a. Go to www.hapmap.org 1b. Select “Browse Project Data”

2. Type search term – “DTNBP1” 2: Search for DTNBP1 2. Type search term – “DTNBP1” Use data source menu to select a different data release. Current release is the default. Search for a gene name, a chromosome band, or a phrase like “insulin receptor”

Chromosome-wide summary data is shown in overview 3: Examine Region Chromosome-wide summary data is shown in overview Default tracks show HapMap genotyped SNPs, named genes from Entrez, and alternative mRNA splicing patterns

3: Examine Region (cont) Use the Scroll/Zoom buttons and menu to change position & magnification As you zoom in, the display changes to indicate more detail.

4: Turn on LD & Haplotype Tracks 4a. Scroll to “Tracks” section and turn on the LD Plot and Haplotype Display tracks 4b. Press “Update Image” These sections allow you to adjust the display and to superimpose your own data on the HapMap.

5: View variation patterns Phased haplotype track shows all 180 chromosomes with alleles colored yellow and blue. Triangle plot shows LD values using r2 or D’ in one or more HapMap population

6: Adjust Track Settings 6a. Select the analysis track to adjust 6b. Press “Configure”

6: Adjust Track Settings (cont) 6c. Adjust populations and display settings. 6d. Press “Configure”

7a. Activate the “tag SNP Picker” and press “Update Image” 7: Turn on Tag SNP Track 7a. Activate the “tag SNP Picker” and press “Update Image”

8a. Select “Annotate tag SNP Picker” and press “Configure…” 8: Adjust Tagger 8a. Select “Annotate tag SNP Picker” and press “Configure…” The tag SNPs are selected on the fly as you navigate around the genome.

8: Adjust Tagger (cont) 8b. Press “Configure” to save changes. Select population Select tagging algorithm and parameters. [optional] upload list of SNPs to be included, excluded, or design scores. 8b. Press “Configure” to save changes.

9. Select the desired “Download” option and press “Go” or “Configure” 9: Generate Reports 9. Select the desired “Download” option and press “Go” or “Configure” Available Downloads: Pairwise LD values Allele & Genotype frequencies Raw genotypes Tag SNPs

9: Generate Reports (cont) The Genotype download format can be saved to disk and loaded into Haploview.

9: Generate Reports (cont) The tag SNP download is the same as you get from TAGGER

Generating Extracts of the HapMap Dataset Find all HapMap characterized SNPs that: 1. Have a MAF > 0.20. 2. Cause a nonsynonymous amino acid change.

1. Surf to hapmart.hapmap.org 1. From www.hapmap.org, click on “HapMart”

2. Select the population of interest 2b. Press “Next” 2a. Choose the population or “All Populations”

3. Select the desired filters 2c. Press “Next” 3a. Check “Allele Frequency Filter” and select MAF >= 0.2 2b. Select “SNPs found in Exons – synonymous coding SNPs”

4. Select output fields 2c. Press “Export” 4a. Choose among several pages of fields. The summary shows active filters and # SNPs to be output. 4b. Select the fields to include in the report. Options at the bottom let you select text or Excel format.

5. Download report

Download the Complete Data Download the entire HapMap data set to your own computer

1. From www.hapmap.org, click on “Bulk Data Downlooad” Surf to www.hapmap.org 1. From www.hapmap.org, click on “Bulk Data Downlooad”

2. Choose the Data Type 2. Select “Genotypes” Raw genotypes Analytic results Allele & genotype frequencies Your own copy of the HapMap Browser Assays

3. Choose the Desired Release 3. Select “latest”

4. Choose the Dataset 4. Select “non-redundant” QC Filtered with duplicate data removed. 4. Select “non-redundant” QC filtered, duplicate data not removed. Not filtered, reudundant data not removed.

5. Download the Files

For Further Information Users guide to HapMap.org http://hapmap.cshl.org/downloads/presentations/users_guide_to_hapmap.pdf HapMap Publications & Guidelines http://hapmap.cshl.org/publications.html.en