Resources at HapMap.Org

Tutorial

Marcela K. Tello-RuizCold Spring Harbor Laboratory

HapMap Phase II Dataset Release #21a, January 2007 (NCBI build 35) 3.8 M genotyped SNPs => 1 SNP/700 bp

International HapMap Consortium (2007). Nature

449:851-861

# polymorphic SNPs/kb in consensus dataset

Goals of This Tutorial

• 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– Add custom tracks of association data– Create publication-quality images

• Generate customized extracts of the entire data set

• Download the entire data set in bulk

This tutorial will show you how to:

Finding HapMap SNPs in a Region of Interest

• Find the TCF7L2 gene• Identify the characterized SNPs in the region• View the patterns of LD (NCBI b35)• Pick tag SNPs (NCBI b35)• Download the region in Haploview format• Upload your own annotations & superimpose

on the HapMap• Make a customized image for publication• View GWA hits & OMIM annotations in the

region (NCBI b36)

HapMap Glossary• LD (linkage disequilibrium): For a pair of SNP

alleles, it’s a measure of deviation from random association (which assumes no recombination). Measured by D’, r2, LOD

• Phased haplotypes: Estimated distribution of SNP alleles. Alleles transmitted from Mom are in same chromosome haplotype, while Dad’s form the paternal haplotype.

• Tag SNPs: Minimum SNP set to identify a haplotype. r2= 1 indicates SNPs are redundant, so either one “tags” the other.

• Questions? help@hapmap.org

1: Surf to the HapMap Browser

1a. Go to www.hapmap.org

1b. Select “HapMap Genome

Browser B35”

ncbi B35: full dataset (includes LD patterns)

ncbi B36: latest, new tracks (e.g., GWA hits)

2: Search for TCF7L2

2. Type search term – “TCF7L2”

Search for a gene name, a

chromosome band, or a phrase like

“insulin receptor”

Region view puts your ROI in

genomic context

3: This exonic region has many typed SNPs.

Click on ruler to re-center image.Default tracks show

HapMap genotyped SNPs, refGenes with exon/intron splicing

patterns, etc.

3: Examine RegionChromosome-wide summary data is

shown in overview

3: Examine Region (cont)

As you zoom in further, the

display changes to include more

detail

Use the Scroll/Zoom

buttons and menu to change position &

magnification

4: Turn on LD & Haplotype Tracks

4b: Press “Update Image”

4a: Scroll down to the “Tracks” section. Turn

on the LD Plot and Haplotype Display

tracks.

These sections allow you to adjust the

display and to superimpose your own data on the

HapMap

5: View variation patternsTriangle plot shows LD

values using r2 or D’/LOD scores in one

or more HapMap population

Phased haplotype track shows all 120 chromosomes with

alleles colored yellow and blue

7: Adjust Track Settings (on the spot)

7b. Adjust population and display settings & press “Configure”

7a. Click on question mark

precedingtrack name

7: Adjust Track Settings (cont)

Select the analysis track to adjust and press “Configure”

8: Turn on Tag SNP Track

8: Activate the “tag SNP Picker” and press

“Update Image”

9: Adjust tag SNP picker

Tag SNPs are selected on the fly as you

navigate around the genome

9a: Click on question mark behind “tag SNP

Picker”

Alternatively, you may select

“Annotate tag SNP Picker” and press

“Configure…”

9: Adjust tag SNP picker (cont)

Select population

Select tagging algorithm and parameters

[optional] upload list of SNPs to be

included, excluded, or design scores9b: Press “Configure”

to save changes

10: Generate Reports

10: Select the desired “Download” option and

press “Go” or “Configure”

Available Downloads:• Individual Genotypes• Population Allele & Genotype frequencies• Pairwise LD values•Tag SNPs

10: Generate Reports (cont)

The Genotype download format can be saved to disk or loaded directly into

Haploview

10: Generate Reports (cont)

The tag SNP download is the same as you get

from TAGGER

…

11: Create your own tracks

11: Upload example file: TCF7L2_annotations.txt

Example:

• Interested in T2DM genetics

• Create file with custom annotations from http://www.broad.mit.edu/diabetes and superimpose on the HapMap

Detailed help on the format is

under the “Help” link

11: Create your own tracks (cont)

Save as a text file!

Some SNPs were typed (known

platform) and others were imputed. Format data for both typed &

imputed SNPs.

Formatted data for the T2DM association results (score is-LOG10 of p-value)

11: Create your own tracks (cont)

Make edits on your own

browser window by clicking on “Edit File…”

11: Create your own tracks (cont)

11: Create your own tracks (cont)

12: Create Image for Publication

12a. Click on “High-res Image”

Click on the +/- sign to

hide/show a section

Mouse over a track until a cross

appears.

Click on track name to drag track up or

down.

Can view file in Firefox, but use other programs

(Adobe Illustrator or Inkscape) to convert to

other formats and/or edit

12b. Click on “View SVG Image in new browser window”

12c. Save generate file with “.svg”

extensions

12: Image for Publication (cont)

Inskape is free and lets you edit and convert to other formats (many

journals prefer EPS)

12: Image for Publication (cont)

13: View GWA hits

13a. Go to www.hapmap.org

13b. Select “HapMap Genome

Browser B36”

13: View GWA hits (cont)

13c. Type search term - “FTO”

Default tracks for B36 include GWA hits, OMIM predicted associations,

and Reactome pathways

14: Read PubMed abstracts for GWA hits

14a: Mouse over a GWA hit to learn more about

the association

14b: Click on the GWA hit to see the study’s PubMed abstract

Use HapMart to Generate Extracts of the HapMap Dataset

Find all HapMap characterized SNPs that:

1. Have a MAF > 0.20 in the Yoruban population panel (YRI)

2. Cause a nonsynonymous amino acid change

1. Go to hapmart.hapmap.org

1. From www.hapmap.org click

on “HapMart”

2. Select data source and population of interest

2a. Choose Yoruba population or “All

Populations”

2b. Press “Next”

Use schema menu to select

dataset

3. Select the desired filters3a. Check “Allele

Frequency Filter” and select MAF >= 0.2

3b. Select “SNPs found in Exons – non

synonymous coding SNPs”

3c. Press “Next”

4. Select output fields

4b. Select the fields to include in the report.

4c. Press “Export”

The summary shows active filters and # SNPs to be

output

Options at the bottom let you select

text or Excel format

4a. Choose among several pages of fields

5. Download report

Bulk downloads: Download the Complete Data• Download the entire HapMap data

set to your own computer

1. Surf to www.hapmap.org

1. From www.hapmap.org, click

on “Bulk Data Download”

Or directly click on “Data”

2. Choose the Data Type

Raw genotypes & frequencies

Analytic results

HapMap Samples

Protocols & assay design

Your own copy of the HapMap

Browser

2. Select “Genotypes”

* Data also available via FTPftp://www.hapmap.org

3. Choose the dataset of interest

Available Genotype Datasets:• Non-redundant: QC+ filtered & redundant data removed• Filtered-redundant: QC+ filtered; duplicated data not removed• Unfiltered-redundant: Includes assays that failed QC

3. Select latest build, fwd_strand

orientation, and “non-redundant”

fwd_strand => same as NCBI reference assemblyrs_strand => same as in dbSNP

Further Information

• HapMap Publications & Guidelineshttp://hapmap.cshl.org/publications.html.en

• Past tutorials & user’s guide to HapMap.orghttp://www.hapmap.org/tutorials.html.en

• Questions?help@hapmap.org

HapMap DCC Present Members (CSHL)Lincoln SteinMarcela K. Tello-RuizLalitha KrishnanZhenyuan Lu

HapMap DCC Former MembersAlbert Vernon SmithGudmundur ThorissonFiona Cunningham