Genic Intolerance to Functional Variation & the Interpretation of Personal Genomes
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003709 Nice plot of the number of rare v common variants in each gene to find outliers particularly tolerant to impactful (eg #LOF) mutations
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003709
Petrovski et al ’13
Patterns…of rare germline variants across 12 cancers http://www.Nature.com/ncomms/2015/151209/ncomms10086/full/ncomms10086.html TCGA v NHLBI exomes finds enriched LOFs + some gene burdening[category scilit]
QT:{{”
“We have around 24,000 genes that make us uniquely human and, until now, it was thought that if any were missing it could cause serious problems.
But new research has found that around 200 of these genes may in fact be completely redundant, without posing any such risk.
By studying the genomes of 2,500 people, researchers have said they were surprised to see around one per cent of these genes were missing entirely in some participants.
More importantly, these particular people had no significant health defects that would be explained by the missing genes.
“}}
Why human disease-associated residues appear as WT in other species http://mbe.oxfordjournals.org/content/31/7/1787.abstract Compensation by their 3D structural neighbors
ALK Mutations Confer Differential Oncogenic Activation
http://www.cell.com/cancer-cell/abstract/S1535-6108%2814%2900393-6 MD modeling better assessing #SNV impact than stats, ie sift
ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma
Scott C. Bresler
Daniel A. Weiser
Peter J. Huwe
…
Ravi Radhakrishnan
Mark A. Lemmon
Yaël P. Mossé
Some initial comparisons of HGMD & OMIM, nice to incl. ClinVar in the future
#PCSK9 Inhibitors Near Market Entry
http://cen.acs.org/articles/93/i13/Cholesterol-Lowering-PCSK9-Inhibitors-Near.html Suggested by natural #LOF lowering LDL via promoting recycling of its receptor
A large set [1171] of rare complete human knockouts
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3243.html ~8% Icelanders have one; from a larger set of ~5K genes w/ #LOFs
Also:
In Iceland’s DNA, New Clues to Disease-Causing Genes – NYTimes.com
http://www.nytimes.com/2015/03/26/science/in-icelands-dna-clues-to-what-genes-may-cause-disease.html
by Carl Zimmer
QT:{{”
The Decode researchers looked for human knockouts in Iceland — and found a lot of them. Nearly 8 percent of Icelanders lack a working version of a gene. All told, the Decode team identified 1,171 genes shut down in Icelandic knockouts.
In a 2012 study, Dr. MacArthur and his colleagues were able to identify just 253 genes knocked out in humans.
“}}
Genotype to phenotype relationships in ASD http://www.nature.com/neuro/journal/v18/n2/abs/nn.3907.html Expression differences in #brain development for LOF-containing, M v F, &c
Also, netbag finds subnets assoc w autism
Removing deleterious mutations in Europeans [v] Africans
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3186.html Comparing nonsynonymous freq. betw. populations HT @obahcall
linkstream2 microblog 