uses PCSK9, a human KO – a pgene motivation
One-and-Done Heart Disease Prevention? Scientists Show It May Be Possible. – The New York Times
https://www.nytimes.com/2026/05/25/health/cholesterol-ldl-gene-therapy.html
Posts Tagged ‘lof’
One-and-Done Heart Disease Prevention? Scientists Show It May Be Possible.
June 7, 2026Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
February 24, 2018Genic 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 and functional implications of rare germline variants across 12 cancer types : Nature Communications : Nature Publishing Group
May 8, 2017Patterns…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]
Scientists discover we don’t need all of out 20,000 genes to survive
October 10, 2015QT:{{”
“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.
“}}
lof paper in Nat Gen
August 28, 2015Analysis of #LOF variants & 20 risk factor phenotypes in 8.6K individuals identifies loci [both well known & new]
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3270.html
NATURE GENETICS | LETTER
Analysis of loss-of-function variants and 20 risk factor phenotypes in 8,554 individuals identifies loci influencing chronic disease
Alexander H Li,
Alanna C Morrison,
Christie Kovar,
L Adrienne Cupples,
Jennifer A Brody,
Linda M Polfus,
Bing Yu,
Ginger Metcalf,
Donna Muzny,
Narayanan Veeraraghavan,
Xiaoming Liu,
Thomas Lumley,
Thomas H Mosley,
Richard A Gibbs
& Eric Boerwinkle
“The Race” to Clone BRCA1
April 25, 2015The Race to Clone #BRCA1 http://www.sciencemag.org/content/343/6178/1462.abstract
Lessons on #LOF mutations, synthetic lethality, silly gene names & the 2-hit hypothesis
synthetic lethality (PARP inhibitors), gene names (RING fingers)
Cholesterol-Lowering PCSK9 Inhibitors Near Market Entry | March 30, 2015 Issue – Vol. 93 Issue 13 | Chemical & Engineering News
April 11, 2015#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
Identification of a large set of rare complete human knockouts : Nature Genetics : Nature Publishing Group
April 3, 2015A 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 autism spectrum disorders : Nature Neuroscience : Nature Publishing Group
February 26, 2015Genotype 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
No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans : Nature Genetics : Nature Publishing Group
January 18, 2015Removing 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 