Biomedical Engineering Reference
In-Depth Information
Figure 4.1
An example of the browser display from www.hapmap.org, accessed by clicking on
the 'HapMap Genome Browser (B35 - full data set)' link. The gene
CHRNA5
was entered into
the 'Landmark or Region' field. The 'Scroll/Zoom' box indicates that the display is showing
28.55 kbp. The 'Overview' panel, or track, indicates the full chromosome on which this gene
lies, and the chromosomal region blown up under the 'Region' panel. The 'Details' panel shows
the SNPs genotyped by HapMap in the selected region, and also displays a pie chart of the
allele frequencies for each SNP in each of the four HapMap population samples: CEU (Centre de
Polymorphisme Humaine, CEPH; Utah residents with ancestry from northern and western Europe),
YRI (Yoruba in Ibadan, Nigeria), CHB (Han Chinese in Beijing, China) and JPT (Japanese in
Tokyo, Japan). The last two tracks display the gene and also tag SNPs which have been selected
according to the default settings: tags represent
r
2
bins where all bin members satisfy
r
2
≥
0.8 with at least one tag in the CEU population. The parameters for tag SNP selection may be
modified using the 'Reports and Analysis' drop-down menu, which is currently set on 'Annotate
LD Plot': click on the arrow to the right, select 'Annotate tag SNP Picker' and choose the desired
parameters. (See Plate 4.1.)
The tagging methods described above are concerned with selecting SNPs that, because of
SNP - SNP correlations or haplotype patterns, serve as good representatives of the variation
observed at additional loci in the region of interest. In addition to that key consideration,
however, it is useful to consider genotyping additional SNPs that are of particular interest; for
example, because of a previously reported association with that SNP or because it is likely
to be of functional significance in a gene (e.g. a non-synonymous coding SNP). To facilitate
such design choices, the HapMap browser allows the user to include a predetermined list of
SNPs in the 'tagging' set. Key functional information for SNPs (such as all coding SNPs
within a gene) can be obtained from the 'gene' and 'SNP' databases of the National Center
for Biotechnology Information (NCBI, www.ncbi.nlm.nih.gov).
An interesting and important design question for a GWAS is the 'genomic coverage'
provided by a given commercial GWAS platform. Recent studies have evaluated coverage
