A well-behaved GWAS yields strong signals for the kinds of genes that contribute to the phenotypic variation.
This provides strong priors for discerning likely causal genes hidden at other loci.
With this in mind, let's revisit the telomere GWAS
medrxiv.org/content/10.110…
This provides strong priors for discerning likely causal genes hidden at other loci.
With this in mind, let's revisit the telomere GWAS
medrxiv.org/content/10.110…
Just going by closest gene, many telomere biology related themes emerge
I colored in this figure from the paper according to closest approach of each gene to a telomere GWAS signal.
Clearly this GWAS is telling us to look at telomere biology.
Clearly this GWAS is telling us to look at telomere biology.
With circular DNA any "naked" end is a sign of DNA damage.
However, since our chromosomes are linear cells have to take precautions to prevent chromosome ends from being "repaired" and fused. jme.bioscientifica.com/view/journals/…
However, since our chromosomes are linear cells have to take precautions to prevent chromosome ends from being "repaired" and fused. jme.bioscientifica.com/view/journals/…
The shelterin complex is part of the solution, preventing DNA repair machinery from inappropriately joining chromosome ends pubmed.ncbi.nlm.nih.gov/26581518/
Many of these genes are in the previous figure but there are some new players.
Many of these genes are in the previous figure but there are some new players.
My eye was drawn to Apollo.
The Apollo protein apparently has 2 roles.
One is in normal DNA repair, but the 2nd is in telomere maintenance where it interacts with TERF2.
The Apollo gene can be a causal gene for Hoyeraal-Hreidarsson syndrome
pubmed.ncbi.nlm.nih.gov/20479256/
The Apollo protein apparently has 2 roles.
One is in normal DNA repair, but the 2nd is in telomere maintenance where it interacts with TERF2.
The Apollo gene can be a causal gene for Hoyeraal-Hreidarsson syndrome
pubmed.ncbi.nlm.nih.gov/20479256/
Apparently the Apollo protein was named for its similarity to the Artemis protein. In Greek mythology, Artemis and Apollo are twins.
This is my favorite picture I found of Artemis and Apollo
twitter.com/kat_anni
This is my favorite picture I found of Artemis and Apollo
twitter.com/kat_anni
The Artemis protein is also a DNA repair enzyme; it was named as a "guardian of the genome", apparently mirroring Artemis' traditional role of guardian of small children:
ncbi.nlm.nih.gov/pmc/articles/P…
ncbi.nlm.nih.gov/pmc/articles/P…
According to ensembl Artemis and Apollo are each other's closest paralog (homolog in the same genome), but the identity is quite low and there are orthologs throughout animals and fungi suggesting Artemis and Apollo split more than 1 billion years ago.
useast.ensembl.org/Homo_sapiens/G…
useast.ensembl.org/Homo_sapiens/G…
The SNP implicating Apollo is rs3838300. According to my analysis, DCLRE1B, the Apollo gene, is only the 2nd closest to this SNP, thus it was not included in my gene set analysis.
SupTable1 lists this as the MAGI3 locus.
eQTL analysis assigned this to AP4B1 (ST4)
SupTable1 lists this as the MAGI3 locus.
eQTL analysis assigned this to AP4B1 (ST4)
Besides DCLRE1B I think I found 5 more telomere-related genes near telomere-length GWAS not discussed in the paper.
This quick STRING analysis picks up one of them, ATM, which, like DCLRE1B, has known interactions with the shelterin proteins. ATM is the closest gene to locus 72.
This quick STRING analysis picks up one of them, ATM, which, like DCLRE1B, has known interactions with the shelterin proteins. ATM is the closest gene to locus 72.
That's probably enough for now so I'll leave you with this golden statue of Apollo as he takes aim at the teal-o-meres.
Should be a good mnemonic for something...
Should be a good mnemonic for something...
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