cautionary in terms of predicting deleterious mutations
Posts Tagged ‘cmg2’
WIRED: Scientists Need More Cat DNA, and Lil Bub is Here to Help
April 3, 2019amusing…
The story has an interesting mendelian disease angle.
https://www.wired.com/story/scientists-need-more-cat-dna-and-lil-bub-is-here-to-help/
Scientists Need More Cat DNA, and Lil Bub is Here to Help
WIRED
Unusual DNA helped make Lil Bub a cat celebrity. Now that genetic data could improve medical care for cats without millions of Instagram followers. Read the full story
The Genomics Landscape: A monthly update from the NHGRI Director – July 2017
July 9, 2017.@Genome_Gov Extramural Grant Portfolio
https://www.Genome.Gov/27569006/july-6-2017-the-nhgri-extramural-grant-portfolio-using-different-approaches-to-fund-genomics-research Nice grid divides programs into PI-initiated/consortia & RFA-solicited v not
Clues from the resilient
July 4, 2017Clues from the resilient
http://www.ScienceMag.org/content/344/6187/970.full Potential 2nd site mutations that neutralize #Mendelian-disease mutations
QT:{{”
“For 127 catastrophic Mendelian diseases (those caused by a single gene such as cystic fibrosis and ataxia-telangiectasia), there are presently 164 genes harboring 685 known recurrent variants that are highly penetrant and causal for deleterious traits, most typically manifesting in individuals before the age of 18 (). …For common diseases, the observed small effect sizes of individual gene variants limit diagnostic potential, and given that most variants identified have an unclear function, how to target the corresponding gene for therapeutic intervention is typically unclear. For rarer Mendelian disorders, although genetics directly implicate a specific gene in a disease, a majority of such cases relate to loss-of-function mutations. Designing small molecules to fix the corresponding broken protein has proven difficult….
The prominent role of second-site mutations and environmental factors that enable resistance to (or buffer against) disease traits has been well established in a multitude of model organisms from yeast to mice (–). Screening for second-site mutations in “resilient” individuals that prevent disease-causing alleles from manifesting their effects could identify targets to which drugs would be designed to disrupt their function, as opposed to targeting the disease-causing gene directly. Genetic studies examining seemingly healthy people have revealed, for example, rare mutations in chemokine (C-C motif) receptor type 5 (the co-receptor for human immunodeficiency virus) that block HIV infection (), and secondary mutations in fetal globin genes that modify the severity of sickle cell disease by buffering primary mutations in β-globin genes ()
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NAR Breakthrough Article: denovo-db: a compendium of human de novo variants
April 3, 2017.@denovodb: a compendium of [initially ~33K] human de novo variants w. phenotype, freely downloadable as a TSV table
https://academic.OUP.com/nar/article-lookup/doi/10.1093/nar/gkw865
QT:{{”
As of July 2016, denovo-db contained 40 different studies and 32,991 de novo variants from 23,098 trios. Database features include basic variant information (chromosome location, change, type); detailed annotation at the transcript and protein levels; severity scores; frequency; validation status; and, most importantly, the phenotype of the individual with the variant.
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denovo-db.gs.washington.edu/denovo-db/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210614/
Leshchiner I, Alexa K, Kelsey P, Adzhubei I, Austin C, Cooney J, Anderson H, King M, Stottmann RW, Ha S, Drummond I, Paw BH, North T, Beier D, Goessling W, Sunyaev S. Mutation mapping and identification by whole genome sequencing. Genome Research (…
March 24, 2017Mutation mapping & identification by WGS
http://Genome.CSHLP.org/content/22/8/1541 SNPtrack server, for uploading reads, does #SNP calls & prioritization
This is a novel method for genetic mapping of mutations.
It accomplishes (1) SNP discovery, (2) mutation localization (including
enumerating allele distribution, assessing recombination breakpoint), and
(3) identifying potential causal variants.
In contrast to previous approaches, this method implemented a HMM model
which does not rely on prior knowledge of SNP variation. The HMM model
predicts the recombination events/breakpoints in increasing distance from
the homozygous SNP sites over whole genome.
Software available: SNPtrack
http://genetics.bwh.harvard.edu/snptrack
Leshchiner I, Alexa K, Kelsey P, Adzhubei I, Austin C, Cooney J, Anderson H, King M, Stottmann RW, Ha S, Drummond I, Paw BH, North T, Beier D, Goessling W, Sunyaev S. Mutation mapping and identification by whole genome sequencing. Genome Research (2012) 22: 1541-1548.
Ambry Freely Providing Aggregate Allele-Frequency Data From 10,000 Sequenced Cancer Patients
March 27, 2016.@AmbryGenetics…Providing Aggregate Allele-Freq. Data From 10k Sequenced Cancer
Patientshttps://www.genomeweb.com/sequencing-technology/ambry-freely-providing-aggregate-allele-frequency-data-10000-sequenced-cancer ExAC-like presentation
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
linkstream2 microblog 