Category Archives: Genetics

Genetics, Philosophy

More human embryos edited

technologyreview.com writes

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.
Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans. […] Reached by Skype, Mitalipov declined to comment on the results, which he said are pending publication. But other scientists confirmed the editing of embryos using CRISPR. “So far as I know this will be the first study reported in the U.S.”

For a few moments of fame, scientists take every risk, even “mass destruction and proliferation”.
It reminds me to the first gene therapy trial by French Anderson who was later stripped of tenure, fired from his faculty position and barred from the campus of his university.

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Software

Safety conditions for genome editing

I would like to see two points added to current CRISPR/Cas9 guidelines.

First of all, the current gene therapies are not being entered into the clinical trial databases on a regular basis. Maybe as the number of treated patients go down to a single individual or as there is no control group. I would really like the recommendation of a priori entry into clinicaltrials.gov or clinicaltrialsregister.eu (or some newly designed gene therapy databases). Just to get towards a clear risk/ benefit ratio.

Second, there should be some way to recognize gene editing. Some barcode as we used it already long ago, an artificial sequence that indicates the new insert. epigenie.com summarized the current approaches by last summer: Gestalt/Jay Shendure, barcode/Stephen R. Quake, scartrace/Jan Philipp Junker, hgRNA/Prasant Mali, mScribe/Tim Lu. Something like the FLAG-tag. Or more recently

R. Kalhor et al., “Rapidly evolving homing CRISPRbarcodes,” Nature Methods, doi:10.1038/nmeth.4108, 2016.
S.D. Perli et al., “Continuous genetic recording with self-targeting CRISPR-Cas in human cells,” Science, doi: 10.1126/science.aag0511, 2016.

 

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Joke

US Government To Officially Recognize GWAS As A Religious Belief

Washington DC – Barack Obama announced today that the United States of America was going to be the first country in the world to officially recognize GWAS as a religious belief.
Genome-Wide Association Studies have long been based on a belief system and the practitioners of GWAS are well-known for their loyalty and dedication to their God – the odds ratio.
Anthropologist, Dr. Amanda Lynn, told The Allium earlier today that the GWAS religion is in fact a relatively new religion, having split from its mother church – the church of latter day genetic linkages – around about the year 2005.

(from http://www.theallium.com/biology/us-government-to-officially-recognize-gwas-as-a-religious-belief/)

 

CC-BY-NC Science Surf accessed 05.11.2025
Allergy, Genetics

Whats’ wrong with the Hutterities and Amish in the NEJM paper?

Following a recent discussion, I looked into more details of the Stein et al. 2016 NEJM paper. It claims that

Despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish.

The first sentence is correct. There is a similar genetic ancestry. Although that doesn’t mean anything as overlapping principal component plots are derived only by frequent SNP alleles that have no major disease impact. Continue reading Whats’ wrong with the Hutterities and Amish in the NEJM paper? →

 

CC-BY-NC Science Surf accessed 05.11.2025
Allergy, Genetics

SMAD3, Vitamin D and asthma

A new JACI paper claims

in three independent birth cohorts (N=60, N=30, N=28) DNA methylation at the SMAD3 promoter was selectively increased in asthmatic children of asthmatic mothers and was associated with risk of childhood asthma.

and argues

although associations between SMAD3 variants rs17228058, rs744910, rs17294280 and asthma have been reported in GWAS, asthma-related SMAD3 methylation differences were unlikely to be influenced by SMAD3 genotype

while I am not convinced as it is common wisdom that

If a SNP interferes with or alters a TF binding site, it could potentially affect both DNA methylation and gene expression independently.

So this possibility needs to be excluded before drawing any conclusions. BTW, SMAD3 is a well know vitamin D target…

1,25-dihydroxyvitamin D3–bound [1,25(OH)2D3-bound] vitamin D receptor (VDR) specifically inhibits TGF-β–SMAD signal transduction through direct interaction with SMAD3.

while so far only IL2 methylation was linked to asthma  (another super Vitamin D target).

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics

Peggy und Böhnhardt – so wenig Wissen, so viel Palaver

Was passiert ist: Am Fundort der sterblichen Überreste von Peggy Knobloch in einem Waldstück wurde 15 Jahres später  DNA gefunden, die mit dem Mikrosatelliten Muster Uwe Böhnhardts übereinstimmt. Eine journalistische Sensation, die beiden bekanntesten Kriminalfälle in Verbindung zu bringen! Verblüffend wie schnell hier Kontamination ausgeschlossen wurde und das obwohl es dieselben Ermittler und dieselben Labore waren, welche mit der DNA gearbeitet haben?

Wie erst jetzt bekannt wurde, handelte es sich bei dem zuständigen Chefermittler im Fall Peggy als auch beim Leiter der späteren “SoKo Bosporus” im Fall der NSU-Morde um ein und dieselbe Person: Den mittlerweile pensionierten Wolfgang Geier.

Die Ermittlungspanne im “Heilbronner Phantom” durch kontaminierten Wattestäbchen ist gerade mal 7 Jahre her. Das sollte auch ein emeritierte Rechtsmediziner im wohlverdienten Ruhestand wissen. Den Vogel aber abgeschossen hat die FAZ mit ausgefeilten Theorien von Böhnhardts Verbindung zu Kindermorden.

bildschirmfoto-2016-10-28-um-08-28-12

Doch es geht noch dümmer, so der ZEIT Titel heute:

bildschirmfoto-2016-10-28-um-08-28-34

Kontamination ist nicht schier unglaublich, sondern die naheliegendste Erklärung. Vielleicht hätte aber auch das forensische Labor mal etwas innovativeres machen müssen, als immer nur die ewig gleichen Panels zu fahren. Zum Beispiel Degradation untersuchen, ein bisschen weiter sequenzieren, miRNAs, Methylierungsmuster bestimmen, 17S RNA, etc., bevor man an die Presse geht?

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Philosophy, Theology

Postfaktisch?

Es ist das Unwort des Jahres. Philipp Sarasin erklärt wieso:

Aussagen über die Welt müssen, mit einem Wort, ‚Sinn ergeben‘. Wenn sie das nicht tun, gibt es im Wesentlichen zwei Möglichkeiten: Sie erweisen sich nach allen Masstäben als falsch oder gelten als uninteressant (oder beides) – oder aber sie werden, früher oder später, zum Ausgangspunkt neuer Wahrheiten, neuer Erkenntnis, neuer Tatsachen. Fakten sind daher seit der Moderne und explizit in unserer Postmoderne „kontingent“, wie der Soziologe Niklas Luhmann sagte: Sie lassen sich nicht ‚letztlich‘ und ‚notwendiger Weise‘ als ‚absolut‘ wahr erweisen […]

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Philosophy

Debunking myths

It is a big question in science how to identify and debunk myths. John Cook and Stephan Lewandowsky gives a free download of their debunking handbook

Debunking myths is problematic. Unless great care is taken, any effort to debunk misinformation can inadvertently reinforce the very myths one seeks to correct. To avoid these “back re effects”, an effective debunking requires three major elements. First, the refutation must focus on core facts rather than the myth to avoid the misinformation becoming more familiar. Second, any mention of a myth should be preceded by explicit warnings to notify the reader that the upcoming information is false. Finally, the refutation should include an alternative explanation that accounts for important qualities in the original misinformation.

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Philosophy, Software

Sind Sie Optimist?

ZEIT Wissen (: Andreas Labert, Christian Schwägerl). Frage an Martin Nowak: Sind Sie Optimist?

Ja, es kommt bei mir ein ganz tiefer Optimismus zustande. Ein Glaube an den Logos, an eine fundamentale Wahrheit, die uns aber nur teilweise zugänglich ist. Man kann natürlich behaupten, es gibt diese Wahrheit nicht, aber was ist die Alternative dazu? Es bliebe eigentlich nur der Nihilismus, die Ansicht, dass nichts einen Sinn ergibt – das würde dann aber die Wissenschaft mit einschließen.

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Software

Evolution is not by chance alone

Evolution isn’t down to chance alone, the New Scientist has been reviewing last year “Arrival of the fittest” by Andreas Wagner. Just by sheer numbers

The problem is that the library is so vast … that the odds of evolution stumbling across the specific “book” it needs … are practically zero. Something else must guide evolution through the library.

And Wagner tells us that Continue reading Evolution is not by chance alone →

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics

Übersicht genetische Beratungsstellen deutschsprachiger Raum 11/2014

überprüftFirmaLinkRegionKlasse
27.10.2014amedes Holding AGhttp://www.amedes-group.comDM
28.10.2014Amway GmbHhttps://nutrilitebodykey.deDL
27.10.2014Bio.logishttps://www.bio.logis.deDML
27.10.2014Bioanalytikshttp://www.http://www.vatest.deB>DF
27.10.2014Biofocus GmbHhttp://www.humane-genetik.deDM
24.10.2014bj diagnostik GmbHhttp://www.bj-diagnostik.deDF
28.10.2014CoGAP GmbHhttp://www.cogap.de/DL
24.10.2014Confidence DNA-Analysen GmbHhttp://www.confidence.atAF
24.10.2014Delphitest GmbHhttp://www.der-gen-test.euDF
24.10.2014Delta-Genhttp://www.deltagen.deDF
27.10.2014DNA Plus - Zentrum für Humangenetik UGhttp://www.dnaplus.de/de/DL
27.10.2014DNA-Diagnosishttp://www.dna-diagnosis.deDX
27.10.2014DNA-Direkthttp://www.dna-direkt.deNL>DF
27.10.2014DNA24http://www.dna-24.deDF
27.10.2014DRK-Blutspendedienst gGmbHhttp://www.blutspende.deDM
27.10.2014Eurofins Medigenomix GmbHhttp://www.medigenomix.deD+intMF
24.10.2014Food GmbH Jenahttp://www.jenagen.deDM
24.10.2014Galantos Genetics GmbHhttp://www.galantos.deDFL
24.10.2014GD Saar GmbHhttp://www.vaterschaftstest-saar.deDF
29.10.2014Genes-Xhttp://www.genes-x.comCH+intL
29.10.2014Genepartner GmbHhttp://www.genepartner.comCH+intL
28.10.2014genEplanet d.o.o.http://www.geneplanet.deSLO>DL
24.10.2014genetikum Neu Ulmhttps://www.genetikum.deDMF
24.10.2014Genolytic GmbHhttp://www.resultan.de/DF
29.10.2014GenoSense Diagnosticshttp://www.pampakerides.comA+intL
31.10.2014GMatchhttp://www.gmatch.orgDLX
27.10.2014Humane Genetik München GmbHhttp://www.humane-genetik.deDM
24.10.2014humatrix AG, Stratipharmhttps://www.humatrix.deDMFL
27.10.2014i-puma.dehttp://www.i-puma.deDF
27.10.2014IBSGhttp://www.ibsg.deDF
24.10.2014ID-Labor GmbHhttp://www.id-labor.deDF
24.10.2014IFB LGC GmbHhttp://www.ifb-lgc.comDF
27.10.2014IFUAG GbRhttp://www.ifuag.deDF
29.10.2014Igenea AGhttp://www.gentest-deutschland.deCHL
24.10.2014IHAhttp://www.iha-direct.deDF
27.10.2014ImaGenes GmbHhttp://www.imagenes-bio.deDX
27.10.2014IMMD GmbHhttp://www.immd.deDMF
27.10.2014IMo Gen GmbHhttp://www.imogen.deDF
27.10.2014Institut für forensische Genetik GmbHhttp://www.forensischegenetik.deDF
24.10.2014JenaGen GmbHhttp://www.jenagen.deDMF
27.10.2014Lauk und Breitling GmbHhttp://www.lauk-breitling.deDF
30.10.2014Lifecodexx AGhttp://lifecodexx.comD+intMX
27.10.2014MV-Genetix GmbHhttp://www.vaterschaftstests.deDF
27.10.2014MVZ GbRhttp://www.imd-berlin.deDM
31.10.2014MVZ GmbHhttp://www.diagnoseklinik.deDML
24.10.2014Myriad Service GmbHhttp://www.myriad-genetics.deDM
29.10.2014Novogenia GmbHhttp://www.novogenia.com/AL
27.10.2014Papacheck GmbHhttp://www.papacheck.deDF
27.10.2014papatest24http://www.papatest24.deDFX
24.10.2014Planton GmbHhttp://www.papacert.deDF
28.10.2014Progenom GmbHhttp://www.progenom.com/CH+intL
28.10.2014Seefeld Medical GmbH/http://www.seefeld-medical.chCHL
27.10.2014ZHLMhttp://www.medizinische-genetik.deDM
27.10.2014ZRMGP Wuerzburghttp://www.drs-mai-schmitt-mulfinger.deDMF
3.11.2014Stada Arzneimittel AGhttp://www.stada-diagnostik.deDMX
3.11.2014Leichter leben in Deutschland Vertriebs GmbHhttp://www.llid-metacheck.deDMX
6.11.2014Institut für angewandte Humangenetik und Onkogenetikhttp://www.humangenetik-prof-froster.deDML
6.11.2014Humangenetische Apparategemeinschafthttp://www.medizinischegenetik-berlin.de/DML
6.11.2014ATCGene molekulare Diagnostikwww.atcgene.deD

 

CC-BY-NC Science Surf accessed 05.11.2025
Genetics, Software

Leaflet.js – layer order, layer address and links

Leaflet is great for mapping in epidemiology with quick results of just cut & pasting a few lines. Problems do start, however, whenever running a more advanced project. It’s a pain, as plugins overwrite functions and basic css layouts. Or layers do not allow clickable links (as propation is being prohibited). Or geojson data that are rejected for whatever reason.
A showcase project, that had been planned for 2 days, took more than 1 week as the documentation is frequently unclear, incomplete and often hard to understand without any (jsfiddle) example. Numerous Google searches helped, as well as peaking into the sourcecode, while also other stack overflow posters have been very helpful. Continue reading Leaflet.js – layer order, layer address and links →

 

CC-BY-NC Science Surf accessed 05.11.2025
Allergy, Genetics, Vitamins

5% of methylated sites escape reprogramming – a new allergy research direction

New Scientist Health has a short report how parents’ lives could change children’s DNA.

Azim Surani at Cambridge University and colleagues have demonstrated that some genes in the developing fetus escape the cleaning mechanism. Surani’s team analysed methylation patterns in a type of fetal cell that later forms a fetus’s own sperm or eggs. We would expect these cells to have been wiped clean when the fetus’s epigenome was reset at the early embryo stage. “However, about 2 to 5 per cent of methylation across the genome escaped this reprogramming,” says Surani.

The current wave of interest stems from three new papers: “The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells” by Guo demonstrates

The transcriptome of human primordial germ cells from the migrating stage to the gonadal stage reveals that both pluripotency genes and germline-specific genes are simultaneously expressed within the same individual cells. The global erasure of DNA methylation creates a super-hypomethylated germline genome.

So at week 10 after gestation, all analyzed 233  primordial germ cells lost their parental methylation marks except of 6% of the male and 8% of the female genome (which is a bit larger) . Unfortunately I did not find a list of genes there that have their parental methylation status transmitted.

Tang from a British consortium “A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development” writes

A unique transcriptome drives extensive epigenome resetting in human primordial germ cells for establishment of totipotency. Some loci associated with metabolic and neurological disorders exhibit resistance to reprogramming and are candidates for transgenerational epigenetic inheritance.

Here evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated ( the number of embryos  being examined is not given). Evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated. When testing for resistant loci, they found that H3K9me3 marked escaping ; resistant regions were also enriched for KAP1 (alias TRIM28) binding sites of ESCs. But still no gene list there.

Sofia Gkountela “DNA Demethylation Dynamics in the Human Prenatal Germline” from the US

performed whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq) of human prenatal germline cells from 53 to 137 days of development. We discovered that the transcriptome and methylome of human germ-line is distinct from both human PSCs and the inner cell mass (ICM) of human blastocysts … Gene expression do not correlate with global changes in DNA methylation.

In this paper finally there is the gene list, I was looking for — basically not demethylated, parentally inherited genes. Persistent methylated regions (also termed DMR, differential methylated regions) in advanced germline cells (AGCs) were seen in 500+ genes as given in table S4:

AADACL2-AS1, ABCA7, ABCC5, ABHD12, ABR, AC093375.1, ACSL4, ACSM1, ACVR1C, ACYP1, ADAMTSL3, ADARB2, ADK, AGBL4, AGK, AGPS, AIG1, AKAP9, AKR1B15, ALPK2, ANK1, ANKHD1, ANKHD1-EIF4EBP3, ANKRD11, ANKRD12, ANKRD19P, ANKRD20A9P, ANKRD24, ANKRD26, ANKRD26P1, ANKRD30BL, ANKRD31, AP2A2, AP3D1, AP4E1, ARAP2, ARHGAP26, ARHGAP39, ARHGAP44, ARHGEF18, ARHGEF4, ARHGEF7, ARID3A, ARL13B, ASB3, ASH1L, ASTN2, ASZ1, ATAD3A, ATF1, ATP11A, ATP13A1, ATP2C1, ATP8A2, ATP9B, AUH, AVEN, BAGE, BAGE2, BAGE3, BAGE4, BAGE5, BASP1P1, BAZ1A, BBS9, BCAS3, BCO2, BCYRN1, BEND3, BEND7, BRE, BRSK2, C14orf159, C15orf37, C1GALT1, C1orf159, C20orf196, C22orf34, C2orf61, C3orf67, C3orf67-AS1, C7orf50, C7orf60, C9orf3, CACNA1B, CACNG4, CALN1, CAMK1D, CARF, CARS2, CC2D2A, CCBL2, CCDC101, CCDC130, CCDC148, CCDC149, CCDC57, CCDC88C, CCDC97, CCNY, CCSER1, CD163, CD2AP, CD46, CDH12, CDH4, CDKAL1, CELF2, CEP70, CERK, CERS4, CFH, CHD2, CHD6, CHODL, CHRM5, CHRNA10, CHRNA4, CLEC16A, CLIC5, CLIC6, CNOT2, CNTN6, CNTNAP2, COG2, COL15A1, COL18A1, COL24A1, COL6A4P2, COLEC11, CORO2B, CPVL, CRTC3, CSMD1, CSMD2, CSNK1D, CTB-7E3.1, CTDP1, CTIF, CTNNA2, CTNNA3, CUBN, CXCR2, CXorf49, CXorf49B, CYCS, CYP3A5, DAPK2, DCDC2C, DDA1, DENND1A, DENND5A, DGUOK-AS1, DIP2C, DLG1, DLK1, DNAH6, DNAH8, DNAJC1, DNER, DOC2GP, DOCK1, DOCK7, DPP10, DSTN, DTNB, DYX1C1, DYX1C1-CCPG1, EBF3, ECHDC2, EDIL3, EEPD1, EFCAB10, EFCAB4B, EFTUD1, EHBP1, EIF2B3, ELMO1, EP400NL, EPHA6, EPPK1, ERC1, ERCC8, ERICH1-AS1, ERP44, ETFA, EVC2, EXD3, EXOC2, EYS, F11-AS1, FAAH, FAM172A, FAM174A, FAM207A, FAM209A, FAM86FP, FANCC, FBN3, FBXO39, FGD4, FGF14, FHIT, FIG4, FLJ30403, FNBP4, FOXN3, FREM3, FZR1, GABRA2, GAS6, GBP2, GCNT7, GDA, GGCX, GLCCI1, GLRA1, GLRA2, GMDS, GNAI1, GOLIM4, GPR75-ASB3, GRIK2, GRM7, GTF3C6, GTPBP10, GUSBP1, H6PD, HCCAT3, HCN4, HDAC4, HECTD4, HEG1, HPGD, HRNR, HS6ST3, HTR7, IFNAR1, IGF2BP3, IGSF11, IGSF22, IGSF9B, IL1RAPL2, IL31RA, IMMP2L, IMPG2, INF2, INTS1, INVS, IPO7, IQCF3, IQCG, IRAK1BP1, ISOC2, ISPD, ITFG1, ITGB1BP2, ITGBL1, JAM3, JAZF1, JMJD1C, KALRN, KATNBL1, KDM3B, KDM4C, KIAA0825, KIAA1328, KIF4A, KIF5B, KLHL20, KLHL3, LANCL3, LDB2, LDLRAD3, LHCGR, LINC00239, LINC00408, LINC00469, LINC00670, LINC00871, LINC00922, LINC01193, LINC01194, LINGO2, LMF1, LOC100128505, LOC100133669, LOC100188947, LOC100289333, LOC101927069, LOC101927280, LOC101927286, LOC101929064, LOC101929387, LOC102723742, LOC145837, LOC283683, LOC285768, LOC286083, LOC442132, LPA, LPPR1, LRP1B, LRRC4C, LTBP1, LUZP2, MAD1L1, MAGT1, MAML3, MAOA, MAP3K15, MAP4K5, MAPK10, MAPK8, MAPK8IP3, MAST2, MCTP1, MCU, MEF2A, MEI4, MELK, METTL15, METTL9, MFHAS1, MIR1273H, MIR518B, MIR518F, MIR520B, MIR548H2, MIR548O2, MIR6130, MIR6744, MOB3B, MOCOS, MTG1, MTMR7, MUC2, MUC5B, MUM1L1, MYO10, MYO5A, MYO9A, MYT1, MYT1L, NAA20, NAALADL2, NAT1, NAV2, NBPF10, NBPF20, NCALD, NCOA2, NEBL, NFATC3, NIFK-AS1, NIPA1, NKAIN2, NKAIN3, NLRP4, NME7, NOC4L, NONO, NPHP4, NQO2, NRXN3, NSUN6, NTSR1, NUBPL, NXN, OGG1, OR8S1, OSBP2, OSBPL6, OSMR, PACS2, PARK2, PARL, PAWR, PCBP3, PCDH19, PCDH9, PCNT, PCNXL2, PCSK6, PDAP1, PDE11A, PDE4D, PGAM1P5, PGAM5, PHKB, PHRF1, PIK3C2A, PIK3CA, PIP5K1B, PKD2L1, PKHD1, PKIB, PLCD1, PLCH1, PLEC, PLOD2, POLR1A, POMK, PPARA, PPARGC1B, PPP2R5C, PRH1, PRH1-PRR4, PRICKLE1, PRKAR1B, PRKCZ, PROSER2, PROSER2-AS1, PRR26, PRUNE2, PTCD3, PTDSS2, PTGFRN, PTPN21, PTPRD, PTPRN2, PYGB, RAB28, RAB3D, RAB3GAP2, RAB3IP, RABGAP1L, RAPGEF6, RBFOX1, RC3H2, RFX7, RGS6, RGS7, RNF115, RNH1, RNU6-52P, RNU6-81P, RPH3AL, RPIA, RPL35A, RPS6KC1, RSPH1, RYR1, S100Z, SCAPER, SCCPDH, SCEL, SCFD2, SCHLAP1, SCMH1, SDHAP3, SDK1, SEC14L1, SEC24D, SEL1L, SEMA3C, SERPINB3, SESN2, SESTD1, SETD1A, SETDB1, SHANK2, SHC2, SIL1, SIN3B, SLC12A3, SLC22A15, SLC24A2, SLC38A10, SLC44A5, SLC6A1, SLC8A1-AS1, SNORD115-1, SNORD115-2, SNTB2, SNTG2, SNX29, SORCS2, SOX5, SPATA5, SPIDR, SPIRE1, SPTB, SPTBN2, SPTLC3, SRD5A1, SRRM4, ST20, ST20-MTHFS, ST6GAL1, STARD9, STIM1, STK31, STK38, STON1-GTF2A1L, STXBP5-AS1, SUPT3H, SYN3, TAF1L, TAS2R19, TENM2, TENM3, THRB, THSD7B, TIMM23B, TJP2, TLK1, TMCC1, TMED1, TMEM132D, TMEM218, TMEM66, TMTC2, TNRC6B, TPST1, TPTE, TRAPPC9, TRIO, TRPC4AP, TRPM2, TRRAP, TSNARE1, TSPAN15, TSPEAR, TSSC1, TTC28, TTC40, TULP4, TYRO3P, TYSND1, TYW1B, UGGT2, UHRF1, ULK4, UNC5D, UNC79, UNC93A, USP13, USP15, USP34, USP50, VGLL4, VPRBP, VPS53, WDPCP, WDR1, WDR19, WDR36, WDR60, WWOX, XAF1, ZBTB20, ZCWPW2, ZFPM2, ZFYVE9, ZKSCAN5, ZMAT1, ZMYM4, ZNF135, ZNF14, ZNF317, ZNF32, ZNF32-AS1, ZNF32-AS2, ZNF32-AS3, ZNF335, ZNF341, ZNF350, ZNF382, ZNF415, ZNF556, ZNF595, ZNF664-FAM101A, ZNF670, ZNF670-ZNF695, ZNF7, ZNF717, ZNF718, ZNF767P, ZNF808, ZNF845, ZNRF1, ZSWIM5

(I dropped two genes as they are only date-formatted numbers in the supplied Excel sheet).

The interesting question for me is if there is an interaction with genes identified earlier in asthma and allergy research. According to the GWAS catalog there are 190 associated genes that match only 9 on the list above: AS1, CLEC16A, CTNNA3, EDIL3, PDE4D, PGAM1P5, SDK1, WDR36. Nothing exciting, in particular no HLA association. WDR36 is the only gene, we published some years ago. I find also only one match (COL15A1) of the 73 low methylation IgE loci published earlier.

Possibly, any of these persistent methylated genes can even stand on its own feet with just one silenced / activated gene  being responsible for the pathology in a pedigree. I cannot identify so many signals in the list above, maybe some IL1 related stuff (IL1RAPL2, IL31RA, IRAK1BP1). CD46 at least is a good candidate as it is known that enhanced CD46-induced regulatory T cells will suppress allergic inflammation after allergen specific immunotherapy.

Unexpectedly, there are also no vitamin D related genes, no VDR, no cytochrome P450 enzymes. Nevertheless I recognize a whole bunch of calcium related genes:  STIM1 (transmembrane protein that mediates Ca2+ influx),  ATP11A + ATP2C1 (ATP dependent Ca2+ transporter), TRPM2 ( another Ca2+ channel), TRPC4AP + RYR1 (sarcoplasmic reticulum calcium channels) and NCALD (a cytosolic calcium transporter).

So would be definitely interesting to test the methylation status of these genes along with vitamin D levels in allergic parents and their kids.

 

CC-BY-NC Science Surf accessed 05.11.2025