2. Computing Haplotype Blocks

In SVS 7 you can compute haplotype blocks manually via the LD interface or automatically using the Gabriel, et al. method. This tutorial will lead you through a combination of both.

A. Automatically Computing Haplotype Blocks

• From the -log10 P + LD plot select the Haplotype Block Set item in the Graph Control Interface and click the Compute… button under the Item tab. Select Visible Markers from the drop-down menu.

Note

Selecting all markers would compute haplotype blocks across the entire 500K dataset.

Figure 3a. LD plot with haplotype blocks.

Notice at the top of the Haplotype Block Detection window it tells you how many markers on how many chromosomes haplotype blocks will be computed for. In this case it is 23 markers active in 1 chromosome.

• Use the default parameters and click Run.

The algorithm produces two haplotype blocks which appear as black outlined pentagons at the top of the LD plot (Figure 3a).

One could argue there should only be one block instead of two. For this reason, SVS 7 makes it easy to manually manipulate blocks when needed and then save the block definitions for subsequent analyses.

B. Manually Manipulating Haplotype Blocks

In this step you will manually define a single block from two separate blocks.

Figure 3b. Haplotype frequencies in Data Console.

• Hover your cursor over the left-edge of Block 2. The mouse cursor changes signifying the block can be resized.
• Left-click on the left edge and hold your mouse button down. Then drag the cursor to the left, expanding Block 2 over Block 1. Blocks being cannibalized will turn grey. Release the mouse button and a new block will be created.

Notice in the Data Console (lower left) how various haplotype statistics are automatically generated for the given block you create (Figure 3b). This block covers 4.453kb and consists of 10 markers. Overall haplotype frequencies are also given which are then broken down for cases and controls, including a 2x2 chi-square p-value.

Note

How many frequencies are displayed in the Data Console is controlled via the Frequency Threshold under the Haplotype Block Set Attribute tab.

IMPORTANT

Case/Control frequencies and associated p-values will only be generated if its respective column is denoted as the dependent variable (magenta) in the original genotype spreadsheet from which the LD plot was created.

C. Removing Markers from a Block

Sometimes it is useful to remove uncorrelated markers from a block.

Each marker is denoted by a light grey pentagon at the top of the LD plot, which we refer to as marker flags.

• Right-click on the uncorrelated marker’s flag (SNP_A-1814230) and select Remove SNP_A-1814230 from Block 2.

The uncorrelated marker now has a dashed line denoting its removal from the block. The haplotype statistics for Block 2 are also updated in the Data Console.

You can save this new block definition for subsequent analyses.

• Select the Haplotype Block Set item in the Graph Control Interface and click the Save button under the Item tab.