Figure 1.
A conceptual picture of our overall analysis.
Each affected individual from different pedigrees captures a different part of the same pathway. The same will be true of different CNVs in different autistic individuals.
Figure 2.
All genes within CNVs were used to find the top ranked pathways in the CNVs (A) and these new pathways along with other a priori created pathways were tested using LoGS (B).
Figure 3.
We pick markers on various chromosome implicated in autism. We then find genes within 50 cM of each marker. Next we ‘align’ each marker to have the same or common origin and then rank genes from this common origin.
Figure 4.
Genes to the left and right of the marker are treated equally (LoGS overview continued).
Here we show how left ranked genes and right ranked genes are placed together in the same ranking.
Figure 5.
Why the closest gene is not necessarily the best gene.
A. Far away genes can be influenced by genes closer to a marker. Thus, we can't just use the closest genes to the marker. B. Since our real locus could be anywhere within the 30 cM window, any of the genes within the window could be the closest gene, and since our best location for the marker is the center of the window, we simply rank the genes from this point to take into account the fact that any of the genes within the window could be the gene closest to some ‘real’ marker. C. The low density of markers means that many genes are ‘covered’ by each marker. The gene of interest may be far from the marker and may not necessarily be the closest gene from the marker.
Table 1.
Copy number gain or loss in the iCNV-5 genes.
Table 2.
LoGS on autism loci. Shown are the top 20 pathways.
Figure 6.
In this figure, we use two loci to illustrate how LoGS works. Say Chromosome 21 has two loci that were implicated in ASD while chromosome 9 has just one locus. We then locate all the genes on chromosomes 1 and 9 and then rank them by their genetic distance from the closest locus on that chromosome (for example the gene between loci 1p21.1 and 1q23.3 is closer to 1q23.3 and thus its distance from 1q23.3 is used). This ranking for all chromosomes (in this example chromosomes 1 and 9) is then collected and we run gene set enrichment analysis as explained in the methods section. The black boxes are markers and the dashed lines represent genes.