BeGenomics.com

[{ "selector": ".qbmos-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".excde-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".sbjua-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".rqprp-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".rbkzq-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".rkzto-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".ulnzb-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".xazkp-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".clkbe-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".bmpwc-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".pzqbk-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".dodgw-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".bzmmu-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".smjef-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".omwzs-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".mnnjl-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".zkfsp-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".rzskr-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".aseor-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".xermm-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".ecajq-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".clbrw-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".becim-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".kppng-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".manqd-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".csqib-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".eeglz-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".jjdqi-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".toezt-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".jlfjx-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".ewsgs-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".ltuci-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".zdawz-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".uunbo-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".miubm-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".xrliw-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".sjppz-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".dueck-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".pdtgb-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".snipq-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".oiwxs-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".orxnr-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".gbseb-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".lzadz-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".pwlno-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".lxsgq-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".ctxkc-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".skeix-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".igplj-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".sriuk-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".glaeo-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".jrtlz-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".uknon-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".dwlzw-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

[{ "selector": ".ofqnm-a", "duration": "500ms", "fill": "forwards", "delay": "0ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }, { "selector": ".lijxq-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-148px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".npcmt-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateX(-157px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".ndskd-a", "duration": "500ms", "fill": "forwards", "delay": "1000ms", "keyframes": [ {"offset": 0, "transform": "translateX(-334px)", "opacity": "1"}, {"offset": 1, "transform": "translateX(0)", "opacity": "1"} ] }, { "selector": ".oepck-a", "duration": "500ms", "fill": "forwards", "delay": "500ms", "keyframes": [ {"offset": 0, "transform": "translateY(calc(600px - 527px))", "opacity": "1"}, {"offset": 1, "transform": "translateY(0)", "opacity": "1"} ] }, { "selector": ".gljdq-a", "duration": "500ms", "fill": "forwards", "delay": "1500ms", "keyframes": [ {"offset": 0, "opacity": 0}, {"offset": 1, "opacity": "1"} ] }]

BeGenomics.com

Scientists identified new risk genes for Neuro-degenerative disorders

www.BeGenomics.com

BeGenomics.com

Neurodegenerative dementias such as AD and PSP are a major cause of morbidity and mortality worldwide.

www.BeGenomics.com

BeGenomics.com

Authors used massively parallel reporter assays to screen noncoding variants reported in genome-wide association studies of two neurodegenerative disorders

www.BeGenomics.com

BeGenomics.com

www.BeGenomics.com

They used MPRA coupled with CRISPR-based validation to identify causal genetic variants underlying 2 neurodegenerative conditions- Alzheimers and progressive supranuclear palsy.

BeGenomics.com

They tested the transcriptional regulatory activity of 5706 noncoding single-nucleotide variants, representing 25 significant loci associated with AD and 9 loci associated with PSP.

www.BeGenomics.com

BeGenomics.com

Identified 320 different functional regulatory variants (frVars) that affect gene expression within 27 of these loci.

www.BeGenomics.com

BeGenomics.com

AD frVars were enriched within microglial enhancers, whereas PSP frVars were enriched within neuronal enhancers

www.BeGenomics.com

BeGenomics.com

They also identified and validated multiple risk loci using CRISPR interference/excision, including complement 4 (C4A) and APOC1 in AD and PLEKHM1 and KANSL1 in PSP.

www.BeGenomics.com

BeGenomics.com

These analyses support a mechanism underlying noncoding genetic risk, whereby common genetic variants drive disease risk in aggregate through polygenic cell type specific regulatory effects.

www.BeGenomics.com

BeGenomics.com

Reference:
Functional regulatory variants implicate distinct transcriptional networks in dementia.

By Yonatan A. Cooper Noam Teyssier et al Science 2022

www.BeGenomics.com

BeGenomics.com

Scientists identified new risk genes for Neuro-degenerative disorders

www.BeGenomics.com

BeGenomics.com

Neurodegenerative dementias such as AD and PSP are a major cause of morbidity and mortality worldwide.

www.BeGenomics.com

BeGenomics.com

Authors used massively parallel reporter assays to screen noncoding variants reported in genome-wide association studies of two neurodegenerative disorders

www.BeGenomics.com

BeGenomics.com

www.BeGenomics.com

They used MPRA coupled with CRISPR-based validation to identify causal genetic variants underlying 2 neurodegenerative conditions- Alzheimers and progressive supranuclear palsy.

BeGenomics.com

They tested the transcriptional regulatory activity of 5706 noncoding single-nucleotide variants, representing 25 significant loci associated with AD and 9 loci associated with PSP.

www.BeGenomics.com

BeGenomics.com

Identified 320 different functional regulatory variants (frVars) that affect gene expression within 27 of these loci.

www.BeGenomics.com

BeGenomics.com

AD frVars were enriched within microglial enhancers, whereas PSP frVars were enriched within neuronal enhancers

www.BeGenomics.com

BeGenomics.com

They also identified and validated multiple risk loci using CRISPR interference/excision, including complement 4 (C4A) and APOC1 in AD and PLEKHM1 and KANSL1 in PSP.

www.BeGenomics.com

BeGenomics.com

These analyses support a mechanism underlying noncoding genetic risk, whereby common genetic variants drive disease risk in aggregate through polygenic cell type specific regulatory effects.

www.BeGenomics.com

BeGenomics.com

Reference:Functional regulatory variants implicate distinct transcriptional networks in dementia. By Yonatan A. Cooper Noam Teyssier et al Science 2022

www.BeGenomics.com

Reference:
Functional regulatory variants implicate distinct transcriptional networks in dementia.

By Yonatan A. Cooper Noam Teyssier et al Science 2022