Category Archives: Genetics

I never read the introduction of an article

I never read the introduction of an article, seldom the discussion section, but I always scan the methods and sometimes (if the methods warrant it) also the tables and figures. It seems that I am not alone here.

The survey indicated that individuals at different career stages valued different sections of scientific papers, and skill in reading the results section develops slowly over the course of an academic career.

So why do we still write papers with an introduction that is longer than 1 sentence?


When his mother Mary had been engaged to Joseph, but before they lived together, she was found to be with child from the Holy Spirit.
19: Her husband Joseph, being a righteous man and unwilling to expose her to public disgrace, planned to dismiss her quietly.
20: But just when he had resolved to do this, an angel of the Lord appeared to him in a dream and said, “Joseph, son of David, do not be afraid to take Mary as your wife, for the child conceived in her is from the Holy Spirit.

incredible? No.

In the study above there are only 44 genes that were involved in parthenogenesis

This identified a polygenic system whereby increased expression of the mitotic protein kinase polo and decreased expression of a desaturase, Desat2, caused facultative parthenogenesis in the non-parthenogenetic species that was enhanced by increased expression of Myc.

COVID19 and type 1 diabetes

There were some diabetes experts at my former work place who opposed against doing COVID19 studies even sending us  epidemiologists into home office while leaving a large study in Munich to the police,  BMW and medical students

Funnily enough, they even warned about any COVID19 research in Cell magazine

… widespread redeployment of world-class expertise from other areas into the current acute phase of COVID-19 research can lead to substantial loss of focus. A longer-term diversion of resources runs the risk of stifling much-needed new basic research and technological breakthroughs that have the potential to revolutionize biomedicine. … A refocus on COVID-19 research activities is likely to engender adverse effects on society’s clear and urgent need for sustained research into major diseases, which will continue to afflict humankind and remain leading causes of death and disability well beyond the end of the acute COVID-19 challenge.

So we had plenty of time to see studies coming up that loss of focus COVID19 is now even inducing  their major disease – early onset of diabetes. The story now goes on to a JAMA metaanalysis and a Nature commentary that confirms the diabetes association in 42 studies including 102 984 youths and showing a

higher incidence rate during the first year of the pandemic compared with the prepandemic period (incidence rate ratio [IRR], 1.14; 95% CI, 1.08-1.21). There was an increased incidence of diabetes during months 13 to 24 of the pandemic compared with the prepandemic period (IRR, 1.27; 95% CI, 1.18-1.37).

The accompanying commentary makes a direct damage of SARS-CoV-2 to  pancreatic cells in children unlikely while the most

probable explanation is that the immune system’s attack on the pancreas is triggered by a COVID-19 infection, which happens with other infections as well, like enteroviruses and hepatitis B.

I can agree on that while my question now: Do  genes play a major role?

Most genetic research of COVID-19 went into disease severity while there was a paper last week describing disease protection by HLA-B*15:01.  As summarized in Science this study of blood donors infected by seasonal coronaviruses showed that

T cells from the subjects with HLA-B*15:01 also reacted aggressively to a fragment of the spike protein from two of the seasonal coronaviruses. This fragment is almost identical to the snippet of SARS-CoV-2’s spike protein that the researchers had tested. The results suggest that when people with the HLA-B variant came down with colds caused by seasonal coronaviruses, they obtained a degree of immunity against similar coronaviruses, including SARS-CoV-2.

For type 1 diabetes  an association with  HLA DR/DQ has been described not only be us but also by many other groups before.

This association is however with class II, not class I as found now in COVID-19. Nevertheless there could be some linkage disequilibrium between class I and II variants although I could not find the B*15 allele in an earlier paper.

Or is the T1D/COVID119 association just by co- or cross activation of the immune system?

Before any expensive profiling of antibodies it may be worthwhile to go for some association testing eg HLA-B*15:01 in T1D as there are known complex transcriptional regulatory circuits in the HLA locus.

Research strategies should never be dogmatic…

An update on the asthma exome

Here is a quick update on some genes of my recent asthma exome paper coming now from the 1 M  exome paper published yesterday as a preprint.

loss of function variants IL1RL1., 12 May 2023

Also ClinVar shows that the IL33 receptor is not “essential” making anti IL33 receptor antibodies like etokimab, itepekimab, tozorakimab a safe therapy although not being effective in any LOF mutation carrier.

The most interesting thing in the preprint is in supplemental table 2 with the s-het values for 16,704 genes. From that table  I have selected  my favorite target  IL33 receptor together with TLR1, ALOX15, GSDMA, IL13 and IKZF3 ( BTNL2 could not be found in the list).

asthma exome, 12 May 2023

IKZF3 would be dangerous to be touched (see my 2008 commentary) while in the 2022 exome paper I  also found  only protective variants in the 5′-UTR but not any LOF variant   – probably as IKZF3 is the only essential gene in the list.

So what’s next? I am still thinking how to reduce my exome set to the causal variants as half of the mutations are probably LD artefacts. And well, it would be super interesting to examine now two extreme inbred populations for their mutation spectrum,  loosing either asthma variants by healthy (Amish) or diseased founders (Tristan da Cunha). Unfortunately there is little hope that this will happen – current science is built more on competition than collaboration.


Legends of science – photo #51

It is one of the most famous photos taken by Raimond Gosling (1926-2015), a former student of Wilkins and Franklin, who

is largely forgotten when the story of DNA is told. To mark the anniversary of his paperclip-inspired contribution, Nature has interviewed him. You can hear the results at … In this interview, a humble Gosling fondly recalls that Franklin’s response to Crick and Watson’s model of the double helix was gracious and sanguine: “She didn’t use the word ‘scooped’. What she actually said was, ‘We all stand on each other’s shoulders’.”

The contribution of Rosalind Franklin has been always controversially discussed with “here, little Raimond, put this round the collimator”. Continue reading Legends of science – photo #51

Any proof for hygiene hypothesis by lockdown babies?

It is an interesting question – does social distancing influence later allergy ? Lawler et al. in November 2021

report the impact of COVID‐19 lockdown in 365 Irish babies at 6 months of age enrolled in the CORAL study. These were a subset of 3773 infants born in two participating major maternity hospitals in Dublin between March and May 2020. Unfortunately only 10% of children participated, so families were self-selected.  Allergic rhinitis was common in both mothers (36%) and fathers (30%) which is higher than reported by Allergy Ireland (26%) and explained by the authors that parental allergy is “higher than the general population, which may have contributed to parental desire to enrol in this study.”

A follow-up in March 2022 in 344 children consecutively shows higher food allergy (4.7% vs 3.5%, NS) when compared to an earlier cohort (BASELINE 2008). Atopic dermatitis increased of 15.5% in the BASELINE study to 25.3% in CORAL (no P reported) which is not unexpected given the interest of parents in an allergy study.

Maybe a short questionnaire at 2026 school entry would be informative than the current study? Nevertheless the authors needed now to analyze their stool samples sitting in the shelves. This is the content of  the March 2023 preprint that has just been published. There may be an association of some bacteria with atopic dermatitis but in the end it is a useless result as the strongest risk factors for atopic dermatitis – parental history and/or FLG mutations – are missing from the presented models

At the end we can safely assume that the 2020 lockdown did not have any influence on allergy prevalence in Ireland.

Arguments against germline therapy

from Tina Rulli “Reproductive CRISPR does not cure disease” in bioethics 2019.

Consider an analogy. Imagine Bill has the following options:
6. Take SICK pill. Bill gets sick.
7. Take SICK pill, then take ANTIDOTE. Bill prevents sickness and remains healthy.
8. Do nothing. Bill stays healthy.
Now imagine that prior to this decision, ANTIDOTE is taken off the market so that it is unavailable to Bill. The unavailability of ANTIDOTE does not mean that Bill gets sick. For Bill has the option to simply not take the sick pill. Bill could just stay healthy (option 8). Offering ANTIDOTE is only morally urgent if it is inevitable that Bill will get sick, i.e., if Bill is forced to take the SICK pill (option 6).

Top 5 talks of the 3rd International Summit on Human Genome Editing

The final statement came by email this morning statement-from-the-organising-committee-of-the-third-international-summit-on-human-genome-editing

Remarkable progress has been made in somatic human genome editing, demonstrating it can cure once incurable diseases. To realise its full therapeutic potential, research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects. The extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed. Heritable human genome editing remains unacceptable at this time.

And well, my subjective selection of  the best talks is also here (unfortunately the video quality is poor and there is no way to timestamp the URL, so you have to recall the time marks below).

As always masterful moderation by Robin Lovell-Badge including the fire alarm ;-) My top 5 talks are

  1. Chinese legislation whitewashed at 1:03:10
  2. David Liu excellent overview at 1:25:14
  3. Filippa Lentzos with a super nice talk on hopes and fears at 2:53:25
  4. Tue Kiran Musunuru with another excellent overview at  2:18:54
  5. Rising star Tina Rulli at 1:28:29

(Jennifer Doudna 4:25:17 was a bit disappointing when talking about my research field involving asthma and microbiome.
The two father mouse of Katsuhiko Hayashi that gained wider attention [Guardian, Nature, …] is found at  3:14:02.



Das neue  Gesetz ist nur zum Teil ein Selbstbestimmungsgesetz, in einigen Passagen liest es sich mehr als Selbstverstümmelung-Ermöglichungsgesetz an, was da als Konzept auf der Webseite des Bundesministeriums für Familie, Senioren, Frauen und  Jugend für den “Personenstandswechsel von Personen im Alter von 14 Jahren” gehandelt wird.

Für Minderjährige bis 14 Jahre oder bei Geschäftsunfähigkeit des Minderjährigen sollen die Sorgeberechtigten die Änderungserklärung gegenüber dem Standesamt abgeben können. Für Minderjährige ab 14 Jahren ist geplant, dass die Minderjährigen die Erklärung selbst mit Zustimmung der Sorgeberechtigten abgeben können. Um die Persönlichkeitsrechte der jungen Menschen zu wahren, sollen Familiengerichte in den Fällen, in denen die Sorgeberechtigten nicht zustimmen, orientiert am Kindeswohl – wie auch in anderen Konstellationen im Familienrecht – die Zustimmung der Eltern auf Antrag des Minderjährigen ersetzen können.
Von zentraler Bedeutung ist eine sachkundige, ergebnisoffene und kostenlose Beratung. Für Minderjährige und ihre Eltern wollen wir daher die Möglichkeit stärken, sich beraten zu lassen. Wir werden sicherstellen, dass Eltern und Minderjährige vor der Entscheidung auf sie aktiv hingewiesen werden. Die Beratung umfasst unter anderem die Familiensituation oder die persönliche Situation des jungen Menschen, Bedarfe, vorhandene Ressourcen sowie mögliche Hilfen, die Verwaltungsabläufe, mögliche Auswirkungen des Vornamens- und Personenstandswechsels, geschlechtliche Entwicklung, Geschlechtsidentität, Umgang mit Varianten der körperlichen Geschlechtsmerkmale, Schutz vor Ausgrenzung und Diskriminierungen sowie Hinweise auf andere Beratungsangebote im Sozialraum. Dabei soll auch auf Beratungsangebote einschlägiger Vereine und Verbände (“peer-to-peer”-Beratung) verwiesen werden.

Ab 14 Jahren gilt bei Kindern das Jugendstrafrecht, das in erster Linie Erziehungsmaßregeln vorsieht, weil ein Mensch mit 14 Jahren zwar viele aber bei weitem nicht alle Entscheidungen wie mit 21 Jahren überblicken kann, schon gar nicht in der Pubertät.

Erziehungsmaßregeln sind neben Erziehungshilfe und Erziehungsbeistandschaft die Erteilung von Weisungen. Weisungen sind Gebote und Verbote, die die Lebensführung der Jugendlichen regeln und dadurch ihre Erziehung fördern und sichern sollen. Weisungen können sich beispielsweise darauf beziehen, bestimmte Orte zu meiden, bei einer Familie oder in einem Heim zu wohnen, eine Ausbildungs- oder Arbeitsstelle anzunehmen, einen Ausgleich mit den Verletzten zu erreichen, an einem Verkehrsunterricht teilzunehmen oder Arbeitsleistungen zu erbringen.

In dem Alter ist die Selbstbestimmung eingeschränkt und ich meine, das sollte so bleiben. Jede/r Pädiater/in hat natürlich Kinder mit Intersex Merkmalen gesehen – auf der Webseite der Universitätsklinik Heidelberg im übrigen noch als Missbildung bezeichnet. Muss man nicht unbedingt so bezeichnen, das Selbstbestimmungsgesetz  ist jedenfalls ein neues Beispiel der ständigen Verrechtlichung (siehe Habermas und andere), die in vielen Fällen mehr schadet als nützt.

Where is the evidence in [trans identified teens] that social transition will help them?

Als Genetiker interessiert mich das Thema auch nicht so sehr aus der woke Perspektive, sondern mehr aus der biologischen Sicht, wo es durchaus auch Fortschritte diese Woche gab. Aber das ist ein anderes Thema.

Some of us are old enough

There is a great comment over at PubPeer about a rather weak and biased paper about 15 years of GWAS studies

Some of us are old enough to remember what was originally promised by genome-wide association studies (GWASs): we would finally discover the genes aetiologically involved in the conditions which till then we had been researching using a combination of linkage and candidate gene association studies. Clearly, this has not happened. With the benefit of hindsight and a myriad actual results we now clearly appreciate what perhaps we should always have realised, which is that common variants do not have substantial effects on phenotypes. GWASs yield complex, difficult to interpret findings which implicate variants but not genes and have not delivered the insights which we were promised they would.

Ein echter Coup

Er hat seit September einen Twitter Account.

Anfang Januar hat er mit einer Bloggerin geredet (“Jesus ist die Inspiration für meine Arbeit, er opferte sich selbst um die Menschheit zu retten”).

Matthias Sander hat ihn nun aufgetrieben und für die NZZ interviewt: Dr. He Jiankui  (“JK”) der Genetiker der Crispr Cas Twins, von dem Nobelpreisträger Baltimore sagt

Everyone deserves a second chance, but He Jiankui’s mistake was so colossal that I would never agree to funding his new experiments in biomedicine.

Was mich interessiert ist weniger sein Score im Golf oder daß er immer noch dasselbe Aktentäschchen wie auf der Bühne des Hongkong  Summits trägt, sondern wie es den Kinder geht.

Continue reading Ein echter Coup

Genetic heritage and language does not always match

This is the interesting outcome of a new PNAS paper (pdf, R) that finds

According to the farming/language dispersal hypothesis, migrations fueled by the shift toward agriculture and animal husbandry in the Holocene have given rise to some of the largest language families identifiable today.

Most researchers thought that genes and language would match while the new paper shows

At the level of individual populations, we estimate more matches (matching enclaves or aligned populations) than mis- matches, but single-population mismatches are present in each continent and within each language family.

The database can be found at

Allergy GWAS hits in VDR binding sites

It seems that I missed an interesting 2017 paper that looked for disease-associated SNPs in canonical DR3 motifs. Only 7 out of 211 traits showed significant hits, one of these was self-reported allergy. When annotating these SNPs, there are only two genes: LINC00299 and TLR1

hg38 position
rs10174949 2:8302018 LINC00299
rs10178845 2:8303773 LINC00299
rs5743566 4:38804221 TLR1
rs2101521 4:38809830 TLR1
rs5743565 4:38804262 TLR1
rs45588337 4:38805607 TLR1
rs55830619 4:38805643 TLR1

So are TLR1 & LINC00299 variant carriers more susceptible to vitamin D induced allergy?

LINC00299 (Long Intergenic Non-Protein Coding RNA 299) is a RNA Gene of largely unknown function, associated so far with allergy only on a genetic level in Framingham,  href=””>23andme and other studies. We don’t know so much here, the function of the long non coding RNAs

depends on subcellular localization. Depending on their niche, they specifically interact with DNA, RNA, and proteins and modify chromatin function, regulate transcription at various stages, forms nuclear condensation bodies and nucleolar organization. lncRNAs may also change the stability and translation of cytoplasmic mRNAs and hamper signaling pathways. Thus, lncRNAs affect the physio-pathological states and lead to the development of various disorders, immune responses, and cancer.

The TLR1 genetic association is found by many genetic studies, while the clinical association is probably more by an infectious origin. TLR1 is a pattern recognition receptor with a specificity for gram-positive bacteria and also included in my forthcoming exome paper as a protective factor for asthma/allergy.  And we are also close to  my earlier review of vitamin D, the microbiome and allergy…

Does any co-infection response during first vitamin D exposure influence allergic sensitisation? There are indeed some hints of an short-lived effect of lung group 2 innate lymphoid cells (ILC2s)

Laboratory mice cohoused for 2 weeks had impaired ILC2 responses and reduced lung eosinophilia to intranasal allergens, whereas these responses were restored in mice cohoused for ≥2 months. … These findings suggest that ILC2s respond dynamically to environmental cues and that microbial exposures do not control long-term desensitization of innate type 2 responses to allergens.





JACI – retractions overdue

JACI is the journal with the poorest experience  that I ever encountered as an author and  as a reviewer.  The editors never adequately responded to numerous errors in an earlier paper where I sent a long letter describing all details.

And it is a nightmare – even now with more than 100 corrigenda in this journal – as the editorial office  even modified correctly submitted images.  Yes, the JACI editor published also falsified data.

Only recently I also found another strange retraction note

The Publisher regrets that this article is an accidental duplication of an article that has already been published in J Allergy Clin Immunol

while the link of this retraction note goes to which is, however, a different paper.

It seem that the journal already lost the overview…