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Article ; Online: The major genetic risk factor for severe COVID-19 is associated with protection against HIV.

Zeberg, Hugo

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 9

Abstract: There are genetic risk factors that influence the outcome of COVID-19 [COVID-19 Host Genetics Initiative, ...

Abstract	There are genetic risk factors that influence the outcome of COVID-19 [COVID-19 Host Genetics Initiative,
MeSH term(s)	COVID-19/genetics ; COVID-19/prevention & control ; Chromosomes, Human, Pair 3/genetics ; HIV Infections/genetics ; HIV Infections/prevention & control ; HIV-1 ; Haplotypes ; Humans ; Patient Acuity ; Risk Factors ; SARS-CoV-2
Language	English
Publishing date	2022-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2116435119
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Article ; Online: The genetic changes that shaped Neandertals, Denisovans, and modern humans.

Zeberg, Hugo / Jakobsson, Mattias / Pääbo, Svante

Cell

2024 Volume 187, Issue 5, Page(s) 1047–1058

Abstract: Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern ... ...

Abstract	Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern humans, and not the other two groups, survived, became numerous, and developed complex cultures. Here, we discuss genetic differences among the groups and some of their functional consequences. As more present-day genome sequences become available from diverse groups, we predict that very few, if any, differences will distinguish all modern humans from all Neandertals and Denisovans. We propose that the genetic basis of what constitutes a modern human is best thought of as a combination of genetic features, where perhaps none of them is present in each and every present-day individual.
MeSH term(s)	Animals ; Humans ; Neanderthals/genetics ; Research ; Hominidae/genetics ; Human Genetics
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.12.029
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: A genomic region associated with protection against severe COVID-19 is inherited from Neandertals.

Zeberg, Hugo / Pääbo, Svante

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 9

Abstract: It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association ... ...

Abstract	It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.
MeSH term(s)	Animals ; COVID-19/genetics ; COVID-19/immunology ; Chromosomes, Human, Pair 12/genetics ; Evolution, Molecular ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Neanderthals/genetics ; Quantitative Trait Loci
Language	English
Publishing date	2021-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2026309118
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Article ; Online: Longitudinal variability in mortality predicts COVID-19 deaths.

Lundberg, Jon O / Zeberg, Hugo

European journal of epidemiology

2021 Volume 36, Issue 6, Page(s) 599–603

Abstract: Within Europe, death rates due to COVID-19 vary greatly, with some countries being severely hit while others to date are almost unaffected. This has created a heated debate in particular regarding how effective the different measures applied by the ... ...

Abstract	Within Europe, death rates due to COVID-19 vary greatly, with some countries being severely hit while others to date are almost unaffected. This has created a heated debate in particular regarding how effective the different measures applied by the governments are in limiting the spread of the disease and ultimately deaths. It would be of considerable interest to pinpoint the factors that determine a country's susceptibility to a pandemic such as COVID-19. Here we present data demonstrating that mortality due to COVID-19 in a given country could have been predicted to some extent even before the pandemic hit Europe, simply by looking at longitudinal variability of death rates in the years preceding the current outbreak. The variability in death rates during the winter influenza seasons of 2015-2019 correlates to excess mortality in 2020 during the COVID-19 outbreak (Spearman's ρ = 0.68, 95 % CI = 0.40-0.84, p < 0.001). In contrast, there was no correlation with age, population density, latitude, GNP, governmental health spending, number of intensive care beds, degree of urbanization, or rates of influenza vaccination. These data suggest an intrinsic susceptibility in certain countries to excess mortality associated with viral respiratory diseases including COVID-19.
MeSH term(s)	Aged ; COVID-19/mortality ; Europe/epidemiology ; Humans ; Longitudinal Studies ; Middle Aged ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-07-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	632614-6
ISSN	1573-7284 ; 0393-2990
ISSN (online)	1573-7284
ISSN	0393-2990
DOI	10.1007/s10654-021-00777-x
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Zs.A 2090: Show issues

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Article ; Online: Functional dissection of two amino acid substitutions unique to the human FOXP2 protein.

Bornschein, Ulrich / Zeberg, Hugo / Enard, Wolfgang / Hevers, Wulf / Pääbo, Svante

Scientific reports

2023 Volume 13, Issue 1, Page(s) 3747

Abstract: The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously ... ...

Abstract	The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously been shown that when they are introduced into the FOXP2 protein of mice they alter striatal synaptic plasticity by increasing long-term depression in medium spiny neurons. Here we introduce each of these amino acid substitutions individually into mice and analyze their effects in the striatum. We find that long-term depression in medium spiny neurons is increased in mice carrying only the T303N substitution to the same extent as in mice carrying both amino acid substitutions. In contrast, the N325S substitution has no discernable effects.
MeSH term(s)	Humans ; Animals ; Mice ; Amino Acid Substitution ; Blood Group Antigens ; Corpus Striatum ; Dissection ; Extremities ; Pan troglodytes ; Forkhead Transcription Factors/genetics ; Repressor Proteins
Chemical Substances	Blood Group Antigens ; FOXP2 protein, human ; Forkhead Transcription Factors ; Foxp2 protein, mouse ; Repressor Proteins
Language	English
Publishing date	2023-03-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-30663-3
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Article ; Online: Fluorescence-Based Measurements of Membrane-Bound Angiotensin Converting Enzyme 2 Activity Using Xenopus Laevis Oocytes.

Fast, Luise / Ågren, Richard / Zeberg, Hugo

Biosensors

2022 Volume 12, Issue 8

Abstract: Functional investigations of enzymes involving cellular expression systems are important for pharmacological studies. The precise control of expression is challenging in transiently transfected mammalian cell lines. Here, we explored the ability of ... ...

Abstract	Functional investigations of enzymes involving cellular expression systems are important for pharmacological studies. The precise control of expression is challenging in transiently transfected mammalian cell lines. Here, we explored the ability of Xenopus laevis oocytes to express a membrane-bound enzyme for functional characterization using standard 96-well plates and a fluorescence-based plate reader assay. We microinjected oocytes with cRNA encoding the angiotensin converting enzyme 2 (ACE2) and measured the enzymatic activity in single oocytes using a commercial fluorescence-based assay. The injected oocytes showed up to a 50-fold increase in fluorescence compared to uninjected oocytes. This fluorescence intensity was dose-dependent on the amount of
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Animals ; Fluorescence ; Mammals ; Oocytes/metabolism ; RNA, Complementary/metabolism ; Xenopus laevis
Chemical Substances	RNA, Complementary ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios12080601
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Article ; Online: The major genetic risk factor for severe COVID-19 is inherited from Neanderthals.

Zeberg, Hugo / Pääbo, Svante

Nature

2020 Volume 587, Issue 7835, Page(s) 610–612

Abstract: A recent genetic association ... ...

Abstract	A recent genetic association study
MeSH term(s)	Animals ; Asia/ethnology ; COVID-19/complications ; COVID-19/genetics ; COVID-19/physiopathology ; Case-Control Studies ; Chromosomes, Human, Pair 3/genetics ; Europe/ethnology ; Genetic Predisposition to Disease ; Genetic Variation/genetics ; Genome-Wide Association Study ; Haplotypes/genetics ; Hospitalization ; Humans ; Linkage Disequilibrium/genetics ; Multigene Family/genetics ; Neanderthals/genetics ; Phylogeny ; Severe Acute Respiratory Syndrome/complications ; Severe Acute Respiratory Syndrome/genetics ; Severe Acute Respiratory Syndrome/physiopathology
Keywords	covid19
Language	English
Publishing date	2020-09-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-020-2818-3
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

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Article ; Online: Low-Resistance silver bromide electrodes for recording fast ion channel kinetics under voltage clamp conditions.

Ågren, Richard / Zeberg, Hugo

Journal of neuroscience methods

2020 Volume 348, Page(s) 108984

Abstract: Background: Two-electrode voltage clamp is a widely used technique for studying ionic currents. However, fast activation kinetics of ion channels are disguised by the capacitive transient during voltage clamp of Xenopus oocytes. The limiting factors of ... ...

Abstract	Background: Two-electrode voltage clamp is a widely used technique for studying ionic currents. However, fast activation kinetics of ion channels are disguised by the capacitive transient during voltage clamp of Xenopus oocytes. The limiting factors of clamp performance include, but are not limited to, amplifier gain, membrane capacitance, and micropipette resistance. Previous work has focused on increasing amplifier gain (e.g.; high performing two-electrode amplifiers) or reducing the membrane capacitance (e.g.; the cut-open technique). New method: The use of an Ag-AgBr electrode with saturated KBr solution to reduce micropipette resistance. Results: The conductivity of 4 M KBr was 37 % higher compared to 3 M KCl and the micropipette resistance was reduced by 19 % when 4 M KBr was used, compared to the standard 3 M KCl solution. Micropipette resistances correlated positively with capacitive transient durations. Neither the current-voltage relationship of the voltage-gated sodium channel, Nav1.7, nor Xenopus oocyte stability were affected by bromide ions. Comparison with existing methods: The de facto standard for two-electrode voltage clamp is 3 M KCl and Ag-AgCl electrodes, which are associated an unnecessarily high micropipette resistance. Elsewise, cut-open voltage clamp techniques are technically demanding and require manipulation of the intracellular environment. Conclusions: The use of an Ag-AgBr electrode with saturated KBr as micropipette solution reduces the capacitive transient in two-electrode voltage clamp recordings. Moreover, the exchange of chloride against bromide ions does not seem to affect oocyte physiology and ion channel kinetics.
MeSH term(s)	Bromides ; Electrodes ; Ion Channels ; Kinetics ; Oocytes ; Silver Compounds
Chemical Substances	Bromides ; Ion Channels ; Silver Compounds ; silver bromide (NHQ37BJZ2Z)
Language	English
Publishing date	2020-10-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2020.108984
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Article ; Online: Response to Comment on "Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals".

Pinson, Anneline / Maricic, Tomislav / Zeberg, Hugo / Pääbo, Svante / Huttner, Wieland B

Science (New York, N.Y.)

2023 Volume 379, Issue 6636, Page(s) eadf2212

Abstract: ... ...

Abstract	Herai
MeSH term(s)	Animals ; Humans ; Neanderthals/genetics ; Neocortex/cytology ; Neocortex/growth & development ; Neural Stem Cells ; Neurogenesis/genetics ; Transketolase/genetics
Chemical Substances	TKTL1 protein, human (EC 2.2.1.1) ; Transketolase (EC 2.2.1.1)
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adf2212
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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Article ; Online: Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals.

Ågren, Richard / Patil, Snehal / Zhou, Xiang / Sahlholm, Kristoffer / Pääbo, Svante / Zeberg, Hugo

Molecular biology and evolution

2023 Volume 40, Issue 6

Abstract: Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. ...

Abstract	Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10-132 and P = 9.2 × 10-69, respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.
MeSH term(s)	Animals ; Humans ; Male ; Alleles ; Dupuytren Contracture/genetics ; Neanderthals/genetics ; Risk Factors
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msad130
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