The effect of knocking out <i>Pou6f2</i> on CCT.

<p>The average CCT (bars represent SEM) from Wild-type (WT) mice and <i>Pou6f2</i>-null (KO) mice is shown. In the Wild-type littermates (n = 10) the cornea was on average significantly (p < 0.01) thicker than observed in the <i>Pou6f2</i>-null mice (n = 6).</p

The CCT for 61 BXD strains is illustrated, with the mean indicated by the bar and standard error of the mean is presented by the red brackets.

<p>The specific BXD strains are indicated along the X-axis. The thickness of the cornea is shown to the right in microns.</p

The four SNPs with the highest p values from the NEIGHBORHOOD Human GWAS Dataset.

<p>None of the SNPs reached genome-wide significance which is 6.4X10^-8.</p

The selective sensitivity of POU6F2 RGC subtypes is demonstrated using the DBA/2J model of glaucoma.

<p>There was a 22% loss of RBPMS-labeled RGCs in aged DBA/2J mice (8 months of age, Aged D2) as compared to young DBA/2J mice (2 months of age, Young D2). There was a dramatic loss of 73% of the POU6F2-positive cells comparing the Young D2 mice to the Aged D2 mice. These data demonstrate the sensitivity of the POU6F2 RGC subtype to glaucoma.</p

Interval map of CCT across the mouse genome is illustrated.

<p>The blue line indicates the total LRS score. The red line illustrates the contribution from the B6 allele and the green line the contribution from the D2 allele. The location across the genome is indicated on the top from chromosome 1 to chromosome X. On the y-axis is the linkage related score (LRS). Notice one significant QTL peak on Chr13 (above the pink Line, p = 0.05) and additional suggestive peaks (above the gray Line).</p

Map of gene locations across Chr. 13.

<p>The haplotype map for the 61 strains in the CCT dataset is shown in the top panel. As indicated at the key on the right, red represents the B6 alleles, green defines the D2 alleles, blue represents regions of the DNA that are heterozygotic and gray is unmapped. The genomic markers used in the mapping process are listed at the bottom of the haplotype map. At the far right is a list of the specific BXD RI strains and the associated CCT measurements going from thick corneas at the top to thin corneas at the bottom. QTL map of CCT on Chr. 13 is shown below the haplotype map. An LRS of above the pink line is statistically significant (p<0.05). A positive additive coefficient (green line) indicates that D2 alleles are associated with higher trait values. The light fill under the peak defines the genomic locus associated with the modulation of CCT. The significant peak for CCT is from 13 to 19 Mb (gray shaded area). Vertical orange lines at the bottom of the plot show the SNPs on Chr. 13.</p

Distribution of POU6F2, in the embryonic eye P15 is illustrated.

<p>In sections stained for POU6F2 (A), there is prominent staining of neuroblasts destined to become retinal ganglion cells (arrow heads). There is also staining of the developing cornea and corneal epithelium (arrow). This staining is specific to the primary antibody for it is not present in sections in which the primary antibody was omitted (B) a secondary only control. Both sections are at the same magnification and the scale bar in B represents 100μm.</p

This is a Manhattan plot over the locus containing <i>POU6F2</i>.

<p>To the left is the p value related to glaucoma in a log₁₀ scale. On the bottom portion of the panel the location of three human genes is shown: <i>VPA41</i>, <i>POU6F2</i> and <i>Pou6F2-AS1</i>. The SNP (rs76319873) with the highest association to POAG is colored purple. The panel insert denotes the imputed quality score (r²) and the appropriate SNPs are colored in the plot.</p

Flow chart explaining all the steps for gene based interaction analysis in discovery (eMERGE) and replication dataset (NEIGHBOR).

<p>Flow chart explaining all the steps for gene based interaction analysis in discovery (eMERGE) and replication dataset (NEIGHBOR).</p

Principal component analysis (PCA) of 5090 samples (glaucoma cases and controls) from eMERGE network.

<p>Eigenvector 1 is on x-axis and eigenvector 2 is on y-axis. Each point is a sample and they are color coded by case and control status.</p