Genetics

Verrückte Experimente

Bisher dachte ich immer, Optogenetik sei die genetische Aufklärung von optischen Anomalien, wie Linsendeformationen oder Netzhauterkrankungen. Aber offensichtlich liege ich damit falsch, wenn ich mir die neue NM Arbeit anschaue, in der ein Hybrid Crispr-Cas9 durch Licht angeschaltet werden kann.

We engineered optogenetic anti-CRISPR variants comprising hybrids of AcrIIA4, a potent Streptococcus pyogenes Cas9 inhibitor, and the LOV2 photosensor from Avena sativa. Coexpression of these proteins with CRISPR–Cas9 effectors enabled light-mediated genome and epigenome editing, and revealed rapid Cas9 genome targeting in human cells.

Die Optogenetik ist ein richtig grosses Feld mittlerweile. Es ist eine interessante Option allemal, die Enzymaktivität intrazellulär an- und abzuschalten zu können.

Die FAZ weiss dazu aber auch ein Experiment, Mäuse auf Knopfdruck im Kreis laufen zu lassen, in dem man den motorischen Cortex über Licht aktiviert. Danke an Juliette Irmer für den Link!

Was für Experimente und was für eine Hybris … Das WSJ zu einem ähnlich gelagerten Tierversuch

The stumbles show the risks of racing ahead with such experiments, even as many governments work to clear regulatory pathways to bring meat, eggs and dairy from gene-edited animals to store shelves. Bioethicists and many geneticists have raised doubts about applying the gene-editing technology to animals and especially humans, given the continued uncertainties in both the science and the lab and field results.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Genetics

Off target sites of the CRISPR CAS babies

Unfortunately we don’t know the genome of the Chinese parents which would be necessary for any prediction of genome mutations in the twins . So far we only know one confirmed off target site from Dr. He’s Hongkong slides that reports 5 mismatches.

reported off target site
reported off target site

At least I would expect for statistical reasons, some 1 bp mismatch, some 2bp, some 3bp…, but not just one 5bp off target site.
So we could check several online services with the know sgRNA sequence that Dr. He used.

CRISPOR

CRISPOR finds one region with 2 mismatches (intergenic) and 13 with 3 mismatches (7 intergenic hits, 5x introns (ST8SIA6, CTD-2532D12.5, CNTN5, C2D3, RABGAP1) and 1x exon of ACACA). This doesn’t match the reported off target sequence.

Cas-OFFinder

Cas-OFFinder identifies 5 regions with 2 mismatches (1x intergenic, 2x sites in LIMCH1, 1x intergenic, 1 in BPIFC).

CCtop (yes, I was waiting for that name :-)

COS finds only one intergenic region with 3 mismatches.

CRISPRSCAN

has the best explanation of what it does but cannot search from sgRNA to off-target as many other online tools.

OFFspotter

is spotting 1 intergenic region with 2 mismatches,  3 with 3 mismatches (2 intergenic, 1 in RP11-238K6.1).

Taken these five different predictions together, I can’t make conclusion but think that we need to resequence the families with much higher coverage (150-200x fold coverage) and even compare the mutations with the phenotype of the children.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Genetics

Das Outdoor Filmfestival, die Masern und das Münchner Gesundheitsamt

Radiodurchsage heute 18:00 in München

Beim Outdoor Filmfestival vor einer Woche war auch eine mit Masern infizierte Person. Wenn Sie auf dieser Veranstaltung waren und jetzt Symptome haben, melden Sie sich bitte bei Ihrem Arzt, denn Masern ist eine meldepflichtige Erkrankung.

Wer um Himmels willen im Gesundheitsamt München hat sich das denn ausgedacht? Es gibt es keine spezifische antivirale Therapie.

Statt eines sinnvollen generellen Impfaufrufs, sollen nun im Wartezimmer multimorbide Patienten angesteckt werden? Das RKI sagt

Die weitere Ausbreitung kann durch die postexpositionelle Immunisierung ungeimpfter bzw. nur einmal geimpfter Kontaktpersonen eingeschränkt werden. Diese sogenannte Riegelungsimpfung sollte so schnell wie möglich, idealerweise innerhalb der ersten 3 Tage nach Exposition, erfolgen.

Auf drei sollte man auch im Referat für Gesundheit zählen können.

Referentin für Gesundheit und Umwelt ist seit 1. September 2015 Stephanie Jacobs. Die Juristin und Mutter von zwei kleinen Kindern bringt einen reichhaltigen Erfahrungsschatz aus ihren bisherigen Berufsstationen im Bayerischen Staatsministerium für Umwelt und Gesundheit/Verbraucherschutz mit.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Genetics

Phenotype of the CRISPR CAS babies

CCR5 annotation, including the known delta32 Mutation and the three mutations introduced by He Jiankui. PAM=Protospacer adjacent motif, DSB=putative double strand break.

From the CCR5 sequence we get the following amino acid sequences

>sp|WT.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

>sp|-32.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPY
IKDSHLGAGPAAACHGHLLLGNPKNSASVSK

>sp|-15.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCS
SQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

>sp|-4.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFP
YSINSGRISRH

>sp|+1.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPY
KSVSILEEFPDIKDSHLGAGPAAACHGHLLLGNPKNSASVSK

The -15/WT genotype will have both, a normal and a slightly shortened CCR5 giving no HIV protection at all. The -4/+1 genotype may suffer the fate of non-sense mediated decay. Here are the amino acid predictions for each genotype (I reverted to Topcocns as Protter had some problems in generating correct plots).

Wildtype: There are 7 transmembrane alpha helices I to VII, connected by three extracellular loops (ECL1–3) and three intracellular loops (ICL1–3). ECL2, forms a β-hairpin structure (Tan 2013).
Known delta 32
Nana -4 genotype has a much shorter predicted amino acid sequence with missing G protein coupling. Resembles delta 32.
Nana +1 genotype is somewhat longer but missing helices VI and VII. No analogue known.
Lulu -15: resembles wild type, however, will be sensitive to allosteric changes by small-molecule CCR5 inhibitors .

From the original AJHG paper, however, also delta 32 carriers may be HIV infected. As there exists also non-CCR5 dependent virus replication, also Nana is at risk of HIV infection when being virus exposed.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Genetics

Putting ‘scientific’ on a bottle of tonic often just a money-making scheme

A reader of the Guardian is now better informed than many scientists

The fact that lots of healthy living schemes claimed to be scientific tells us something about the power, authority and appeal of science at the time. It’s easy to be cynical and suggest that putting ‘scientific’ on a bottle of tonic was just a crude money-making scheme – and sometimes that was the case. But clearly some of the people involved believed that they were right, and that they were doing important scientific or medical work. They had been trained in the same institutions and taken the same exams as their critics. So how could they disagree over whether they were ‘faddists’ or ‘scientists’? And how can we as lay people tell the difference?
Part of the problem is the difficulty in defining science. While it’s practised by all sorts of different people, with different qualifications in different places, one thing that’s supposed to be constant is the scientific method. Many scientists, and most of us who study science, recognise that there isn’t actually a single, unifying ‘Scientific Method’, but that doesn’t stop people trying to find it, and there’s a ‘common sense’ version that’s often suggested, which runs something like this:
(1) Form hypothesis (2) design experiment to test hypothesis (3) run experiment (4) adjust hypothesis according to results

 

CC-BY-NC Science Surf , accessed 07.05.2026
Joke, Software

A mistake in the operating room

Found at https://www.nature.com/articles/ncpuro0294#article-info via https://twitter.com/MaartenvSmeden/status/1071138625415458817

A mistake in the operating room can threaten the life of one patient; a mistake in statistical analysis or interpretation can lead to hundreds of early deaths. So it is perhaps odd that, while we allow a doctor to conduct surgery only after years of training, we give SPSS® (SPSS, Chicago, IL) to almost anyone. Moreover, whilst only a surgeon would comment on surgical technique, it seems that anybody, regardless of statistical training, feels confident about commenting on statis- tical data. If we are to bring the vast efforts of research to fruition, and truly practice evidence- based medicine, we must learn to interpret the results of randomized trials appropriately.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Philosophy, Software

ICMJE Conflicts of Interest – spyware?

I dont’t understand why the ICMJE Conflicts of Interest of the Vancouver group is NOT distributed as a standard PDF but as an Adobe Form that can be opened only after installing a lot of unnecessary software that opens a lot of unnesssary ports transmitting a lot of unnecessary data. This is how it looks natively on a Mac

 

and this is how it should look like

Adobe Acrobat Reader DC does not even allow printing into a PDF, clearly spyware behavior forcing data collection on an unknown destination.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Vitamins

Viel hilft viel

Immer wieder wird Deutschland ein flächendeckender Vitamin-D-Mangel attestiert. So schrieb beispielsweise die Deutsche Gesellschaft für Ernährung in ihrem Bericht, den sie im Sommer veröffentlichte, rund 30 Prozent der Erwachsenen seien nicht ausreichend mit Vitamin D versorgt. Wobei Ältere als Risikogruppe gelten und bei Seniorinnen der Mangel aber ausgeprägter ist als bei Männern. Für Personen mit hohem Risiko für einen Vitamin-D-Mangel erachtet es die DGE für notwendig, ein Vitamin-D-Präparat einzunehmen, um den Bedarf zu decken. Evidenz für eine generelle Substitution gibt es zwar nicht. Aber anscheinend führen solche Berichte und das zugehörige Medien-Echo dazu, dass eigenmächtig ohne Rücksprache mit Arzt oder Apotheker Vitamin D eingenommen wird – und zwar nach dem Motto: „viel hilft viel“

Wer glaubt schon der Deutsche Gesellschaft für Ernährung? Immerhin doch Einige: Die Deutschen Apothekerzeitung berichtet aktuell über zwei Fälle von akuten Nierenversagen bei ausgeprägter Hyperkalzämie,.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Genetics, Theology

All humans, and two ancestors?

Daily Mail reports a study in Human Evolution with comments at phys.org

A scientific study has prompted speculation that all modern humans could have descended from a solitary pair who lived 100,000 to 200,000 years ago.
Scientists surveyed the genetic ‘bar codes’ of five million animals – including humans – from 100,000 different species and the results have prompted speculation that we sprang from a single pair of adults after a catastrophic event almost wiped out the human race.
These bar codes, or snippets of DNA that reside outside the nuclei of living cells, suggest that it’s not just people who could have come from a single pair of beings, but nine out of every 10 animal species, too.

I have heard that before.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Joke

The not so revolutionary phenotype

While scanning the internet for the crispr’d babies I found some bizarre accounts. One of these is “Revolutionary Phenotype” by Jean-Francois Gariépy, a book to appear in late 2018, and more fi than sci.

Suppose you want to have a child, but instead of reproducing in the traditional fashion, you and your mate opt to store your genetic information on a computer. Then, while your genes are digitally stored on the computer’s hard drive, you decide to make a few minor edits—just some slight improvements to ensure your kid will be healthy. You then dump your revised digital genome into a series of DNA molecules, which you inject into a human egg that has been stripped of its own native genome. Nine months later, your flesh- and-blood child is born, and you and your family proceed with your deeply satisfying life. You end up never regretting the decision you have made to modify a few genes in your child’s DNA. Your child likes it too since he has better health and strength compared to most of his peers. He’s already dreaming of having his own genetically- modified children.

Humans are not only determined by their genome. And the human genome is a bit more than a digital sequence. But maybe this misunderstanding is intended to increase sales.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Genetics

How does the soma to germline transfer work?

I never had problems to understand environmental induced sperm methylation as spermatozoa of animals are produced continuously by meiotic division.  But I learned that in humans all ova are produced before birth, so how could these ever be influenced by an environmental exposure? It seems that the dogma of prefabricated eggs is wrong as described already in 2012.

Rare mitotically active cells have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-μm oocytes

So there is a lifelong chance that environmental exposures both in fathers and mothers can be transmitted to the offspring “fat eggs, fat offspring” – there is no Weismann Barrier. (This remains also an important question as somatic gegen therapy could accidentally introduced germline changes – at least in theory).

But how does any soma to germline transfer work? A new paper examined this  in more detail. They found that the negative regulator of sperm activation in C elegans, SWM-1, is produced in body wall muscle, then secreted into the body cavity. Whenever it enters the gonad it finds it target TRY-5, a spermiogenesis activator, that influences sperm success.

So to the more conventional soma to germline theories of persistent methylation changes or RNA fragments ( as described in a recent review) there maybe more possibilities like microbiome transfer.

 

CC-BY-NC Science Surf , accessed 07.05.2026
Philosophy

One of the things I’ve never done very well

According to chess24.com

Magnus Carlsen demolished Fabiano Caruana 3:0 in rapid tiebreaks on Wednesday to retain his World Championship title for another two years. He was defiant afterwards about his decision not to play on in Game 12, saying Garry Kasparov and Vladimir Kramnik were, “entitled to their stupid opinions”, while he explained, “one of the things I’ve never done very well is listen to other people’s advice. I’ve always gone my own way… and it’s brought me this trophy today!”

 

CC-BY-NC Science Surf , accessed 07.05.2026
Philosophy

Was bleibt

In erster Linie bleiben die spinnerten Menschen im Gedächtnis haften, vermutlich weil sie jene Welt verkörpern, die allein mit der Kraft des Verstandes nicht zu durchdringen ist (Hans Kratzer)

 

CC-BY-NC Science Surf , accessed 07.05.2026