Posts Tagged ‘aloft’

Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes

Sunday, February 25th, 2018

Genic Intolerance to Functional Variation & the Interpretation of Personal Genomes Nice plot of the number of rare v common variants in each gene to find outliers particularly tolerant to impactful (eg #LOF) mutations

Petrovski et al ’13

Scientists discover we don’t need all of out 20,000 genes to survive

Saturday, October 10th, 2015

“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 the Wild-Type in Other Species: Genome-Scale Structural Evidence for the Compensation Hypothesis

Monday, September 14th, 2015

Why human disease-associated residues appear as WT in other species Compensation by their 3D structural neighbors

ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma: Cancer Cell

Friday, May 22nd, 2015

ALK Mutations Confer Differential Oncogenic Activation 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


Automated validation of genetic variants from large databases: ensuring that variant references refer to the same genomic locations

Sunday, April 26th, 2015

Some initial comparisons of HGMD & OMIM, nice to incl. ClinVar in the future

Cholesterol-Lowering PCSK9 Inhibitors Near Market Entry | March 30, 2015 Issue – Vol. 93 Issue 13 | Chemical & Engineering News

Saturday, April 11th, 2015

#PCSK9 Inhibitors Near Market Entry 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

Friday, April 3rd, 2015

A large set [1171] of rare complete human knockouts ~8% Icelanders have one; from a larger set of ~5K genes w/ #LOFs


In Iceland’s DNA, New Clues to Disease-Causing Genes –

by Carl Zimmer
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

Thursday, February 26th, 2015

Genotype to phenotype relationships in ASD 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

Sunday, January 18th, 2015

Removing deleterious mutations in Europeans [v] Africans Comparing nonsynonymous freq. betw. populations HT @obahcall

Geneticists tap human knockouts

Saturday, November 1st, 2014

Sequenced genomes reveal mutations that disable single genes and can point to new drugs.

Ewen Callaway

28 October 2014 Corrected:
29 October 2014

You should also read the Corrections to this article


The poster child for human-knockout efforts is a new class of drugs that block a gene known as PCSK9 (see Nature 496, 152–155; 2013). The gene was discovered in French families with extremely high cholesterol levels in the early 2000s. But researchers soon found that people with rare mutations that inactivate one copy ofPCSK9 have low cholesterol and rarely develop heart disease. The first PCSK9-blocking drugs should hit pharmacies next year, with manufacturers jostling for a share of a market that could reach US$25 billion in five years.

“I think there are hundreds more stories like PCSK9 out there, maybe even thousands,” in which a drug can mimic an advantageous
loss-of-function mutation, says Eric Topol, director of the Scripps Translational Science Institute in La Jolla, California. Mark Gerstein, a bio­informatician at Yale University in New Haven, Connecticut, predicts that human knockouts will be especially useful for identifying drugs that treat diseases of ageing. “You could imagine there’s a gene that is beneficial to you as a 25-year-old, but the thing is not doing a good job for you when you’re 75.”