Arbeitgruppe: Staff of the Department of Molecular Medicine
Staff of the Department of Molecular Medicine

Overview

The aim of our research is to identify human genetic variants that make some people naturally resistant to certain infectious diseases and to find out how these variants function. At present, our work concentrates on malaria and tuberculosis. Relevant genetic variants are being identified by comparing large groups of patients and healthy persons. As most if not all of those variants identified so far as having a significant impact are located outside structural genes, the disclosure of their function poses a great challenge. We teamed up with Wouter de Laat and his group at the Hubrecht Institute in Utrecht, the Netherlands, who is a stem-cell researcher and expert in analysing the non-coding genome. Using methods such as the so-called C-technologies and DNase-Seq footprinting, we stepwise approach the functional regulatory events involved. They are expected to reveal defense mechanisms or other metabolic pathways influencing the courses of infection. Thereby, their functions can hint at previously unrecognized approaches to treatment and prevention.

In order to study large numbers of patients and unaffected persons, the department closely co-operates with the Kumasi Centre for Collaborative Research (KCCR), a research institute in the West African rain forest jointly run by the Bernhard Nocht Institute, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, and the Ministry of Health of the Republic of Ghana.

Research Projects

Human genetic resistance to malaria

Christian Timmann, Kathrin Schuldt, Christa Ehmen, Jürgen Sievertsen

The common fatal complications of childhood malaria are coma and convulsions, sudden-onset severe anaemia, acidosis and respiratory distress. In the past years, our colleagues at Komfo Anokye Teaching Hospital and at the Kumasi Centre for Collaborative Research (KCCR) in Kumasi, Ghana, have carefully examined 2645 children with life-threatening malaria complications and, for comparison, 3050 healthy children. To study mild malaria, they have in rural communities followed 465 children by weekly examinations over an entire rainy season of eight months.

The role of human genetics in natural protection against malaria has been known since more than fifty years, initially from evidence of malaria protection by red-blood cell disorders such as the sickle-cell trait and thalassaemias. However, the mechanisms of protection by these disorders have remained largely unknown. In our study group of severe malaria, we have found that, whereas the sickle-cell trait protects against all forms of the disease, thalassaemia protects against severe anaemia only and haemoglobin C only against cerebral malaria, i.e. coma and convulsions. In the same study group, we have performed a genome-wide association study (GWAS). We found two regions of the human genome associated with protection from the disease, but the underlying modes of action remain unknown.

At present, we perform in our Ghanaian study groups selected candidate gene studies, we further refine the GWAS analysis and, most importantly, try to identify the mechanisms of malaria protection underlying the association signals obtained by GWAS.

Signals obtained in a genome-wide association study on severe malaria.

Human genetic resistance to tuberculosis

Thorsten Thye, Birgit Muntau, Gerd Ruge

Approximately 90% of humans are considered to be naturally protected against tuberculosis (TB). It is our approach to search for human genetic factors that mediate this natural protection in order to identify the human metabolic and immunological pathways involved and to use this information to develop new intervention strategies.

In collaboration with colleagues from Accra and Kumasi in Ghana we have characterized more than 2000 HIV-negative patients with sputum-positive TB and more than 3500 unaffected persons. Cultures of mycobacteria are available from 1500 patients for detailed characterization including biochemical and genetic analyses.

We found that variants of the MBL, CTLA4, IL10, MCP1, ALOX5, TNFRSF1B, and IRGM genes influence certain features of the infection and performed a genome-wide association study (GWAS), which indicated association signals on chromosomes 11 and 18. These signals were confirmed statistically in collaboration with partners from the Universities of Oxford, Cambridge and Leiden, who had studied patients from The Gambia and Malawi, Russia and Indonesia, respectively. Both association signals are located in intergenic regions of the human genome, and major efforts are currently being undertaken to determine their functional effects. In addition, a further GWAS is being performed in a German study group enrolled by the German “TB-or-not-TB” consortium.

GWAS signal of association with pulmonary tuberculosis on chromosome 11 including data imputed from the "1000 Genomes Project".

Publication Highlights

Abteilung Molekulare Medizin

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration.
Curtis J, Luo Y, Zenner HL, Cuchet-Lourenço D, Wu C, Lo K, Maes M, Alisaac A, Stebbings E, Liu JZ, Kopanitsa L, Ignatyeva O, Balabanova Y, Nikolayevskyy V, Baessmann I, Thye T, Meyer CG, Nürnberg P, Horstmann RD, Drobniewski F, Plagnol V, Barrett JC, Nejentsev S.
Nat Genet. 2015 May;47(5):523-7. doi: 10.1038/ng.3248. Epub 2015 Mar 16.

Evidence of promiscuous endothelial binding by Plasmodium falciparum-infected erythrocytes.
Esser C, Bachmann A, Kuhn D, Schuldt K, Förster B, Thiel M, May J, Koch-Nolte F, Yáñez-Mó M, Sánchez-Madrid F, Schinkel AH, Jalkanen S, Craig AG, Bruchhaus I, Horstmann RD.
Cell Microbiol. 2014 May;16(5):701-8. doi: 10.1111/cmi.12270. Epub 2014 Feb 24.

Genome-wide association study indicates two novel resistance loci for severe malaria.
Timmann C, Thye T, Vens M, Evans J, May J, Ehmen C, Sievertsen J, Muntau B, Ruge G, Loag W, Ansong D, Antwi S, Asafo-Adjei E, Nguah SB, Kwakye KO, Akoto AO, Sylverken J, Brendel M, Schuldt K, Loley C, Franke A, Meyer CG, Agbenyega T, Ziegler A, Horstmann RD.
Nature. 2012 Sep 20;489(7416):443-6. doi: 10.1038/nature11334. Epub 2012 Aug 15.

Common variants at 11p13 are associated with susceptibility to tuberculosis.
Thye T, Owusu-Dabo E, Vannberg FO, van Crevel R, Curtis J, Sahiratmadja E, Balabanova Y, Ehmen C, Muntau B, Ruge G, Sievertsen J, Gyapong J, Nikolayevskyy V, Hill PC, Sirugo G, Drobniewski F, van de Vosse E, Newport M, Alisjahbana B, Nejentsev S, Ottenhoff TH, Hill AV, Horstmann RD, Meyer CG.
Nat Genet. 2012 Feb 5;44(3):257-9. doi: 10.1038/ng.1080.

A -436C>A polymorphism in the human FAS gene promoter associated with severe childhood malaria.
Schuldt K, Kretz CC, Timmann C, Sievertsen J, Ehmen C, Esser C, Loag W, Ansong D, Dering C, Evans J, Ziegler A, May J, Krammer PH, Agbenyega T, Horstmann RD.
PLoS Genet. 2011 May;7(5):e1002066. doi: 10.1371/journal.pgen.1002066. Epub 2011 May 19.

Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.
Thye T, Vannberg FO, Wong SH, Owusu-Dabo E, Osei I, Gyapong J, Sirugo G, Sisay-Joof F, Enimil A, Chinbuah MA, Floyd S, Warndorff DK, Sichali L, Malema S, Crampin AC, Ngwira B, Teo YY, Small K, Rockett K, Kwiatkowski D, Fine PE, Hill PC, Newport M, Lienhardt C, Adegbola RA, Corrah T, Ziegler A; African TB Genetics Consortium; Wellcome Trust Case Control Consortium, Morris AP, Meyer CG, Horstmann RD, Hill AV.
Nat Genet. 2010 Sep;42(9):739-41. doi: 10.1038/ng.639. Epub 2010 Aug 8.

All Publications

2016

The Prevalence of Sickle Cell Disease and Its Implication for Newborn Screening in Germany (Hamburg Metropolitan Area).
Grosse R, Lukacs Z, Cobos PN, Oyen F, Ehmen C, Muntau B, Timmann C, Noack B.
Pediatr Blood Cancer. 2016 Jan;63(1):168-70. doi: 10.1002/pbc.25706. Epub 2015 Aug 14.

A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients.
Hölscher C, Heitmann L, Owusu-Dabo E, Horstmann RD, Meyer CG, Ehlers S, Thye T.
Mediators Inflamm. 2016;2016:4245028. doi: 10.1155/2016/4245028. Epub 2016 Feb 10.

Molecular Diagnosis of Human Taenia martis Eye Infection.
Koch T, Schoen C, Muntau B, Addo M, Ostertag H, Wiechens B, Tappe D.
Am J Trop Med Hyg. 2016 Feb 29. pii: 15-0881. [Epub ahead of print]

Molecular Identification of Zoonotic Tissue-Invasive Tapeworm Larvae Other than Taenia solium in Suspected Human Cysticercosis Cases.
Tappe D, Berkholz J, Mahlke U, Lobeck H, Nagel T, Haeupler A, Muntau B, Racz P, Poppert S
J Clin Microbiol. 2016 Jan;54(1):172-4. doi: 10.1128/JCM.02171-15. Epub 2015 Oct 21.

2015

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration.
Curtis J, Luo Y, Zenner HL, Cuchet-Lourenço D, Wu C, Lo K, Maes M, Alisaac A, Stebbings E, Liu JZ, Kopanitsa L, Ignatyeva O, Balabanova Y, Nikolayevskyy V, Baessmann I, Thye T, Meyer CG, Nürnberg P, Horstmann RD, Drobniewski F, Plagnol V, Barrett JC, Nejentsev S.
Nat Genet. 2015 May;47(5):523-7. doi: 10.1038/ng.3248. Epub 2015 Mar 16.

No significant impact of IFN-γ pathway gene variants on tuberculosis susceptibility in a West African population.
Meyer CG, Intemann CD, Förster B, Owusu-Dabo E, Franke A, Horstmann RD, Thye T.
Eur J Hum Genet. 2015 Aug 5. doi: 10.1038/ejhg.2015.172.

Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients.
Balabanova Y, Nikolayevskyy V, Ignatyeva O, Kontsevaya I, Mironova S, Kovalyov A, Kritsky A, Rodionova Y, Fedorin I, Casali N, Hooper R, Horstmann RD, Nejentsev S, Hoffner S, Nuernberg P, Drobniewski F.
Infect Genet Evol. 2015 Dec;36:517-23. doi: 10.1016/j.meegid.2015.08.028. Epub 2015 Aug 28.

Polymorphism of X-linked CD40 ligand gene associated with pulmonary tuberculosis in the Han Chinese population.
Hu CY, Zhang XA, Meyer CG, Thye T, Liu W, Cao WC.
Genes Immun. 2015 Sep;16(6):399-404. doi: 10.1038/gene.2015.20. Epub 2015 Jun 4.

CCN1 mutation is associated with atrial septal defect.
Perrot A, Schmitt KR, Roth EM, Stiller B, Posch MG, Browne EN, Timmann C, Horstmann RD, Berger F, Özcelik C.
Pediatr Cardiol. 2015 Feb;36(2):295-9. doi: 10.1007/s00246-014-1001-8. Epub 2014 Aug 19.

Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms.
Prado M, Eickel N, De Niz M, Heitmann A, Agop-Nersesian C, Wacker R, Schmuckli-Maurer J, Caldelari R, Janse CJ, Khan SM, May J, Meyer CG, Heussler VT.
Autophagy. 2015;11(9):1561-79. doi: 10.1080/15548627.2015.1067361.

Vaccine introduction in the Democratic People's Republic of Korea.
Marks F, Nyambat B, Xu ZY, von Kalckreuth V, Kilgore PE, Seo HJ, Du Y, Park SE, Im J, Konings F, Meyer CG, Wierzba TF, Clemens JD.
Vaccine. 2015 May 11;33(20):2297-300. doi: 10.1016/j.vaccine.2015.03.005. Epub 2015 Mar 10.

Fatal Human Meningoencephalitis due to Halicephalobus Nematodes, Germany.
Monoranu CM, Müllges W, Keppler M, Brehm K, Ondrejka SL, Muntau B, Tannich E, Müller-Hermelink HK, Tappe D.
Open Forum Infect Dis. 2015 May 22;2(2):ofv061. doi: 10.1093/ofid/ofv061. eCollection 2015 Apr.

Human case of Onchocerca lupi infection, Germany, August 2014.
Bergua A, Hohberger B, Held J, Muntau B, Tannich E, Tappe D.
Euro Surveill. 2015 Apr 23;20(16). pii: 21099.

Molecular Diagnosis of Abdominal Armillifer grandis Pentastomiasis in the Democratic Republic of Congo.
Tappe D, Sulyok M, Rózsa L, Muntau B, Haeupler A, Bodó I, Hardi R.
J Clin Microbiol. 2015 Jul;53(7):2362-4. doi: 10.1128/JCM.00336-15. Epub 2015 May 6.

Echinococcus vogeli in immigrant from Suriname to the Netherlands.
Stijnis K, Dijkmans AC, Bart A, Brosens LA, Muntau B, Schoen C, Barth TF, van Gulik T, van Gool T, Grobusch MP, Tappe D.
Emerg Infect Dis. 2015 Mar;21(3):528-30. doi: 10.3201/eid2103.141205. No abstract available.

2014

Evidence of promiscuous endothelial binding by Plasmodium falciparum-infected erythrocytes.
Esser C, Bachmann A, Kuhn D, Schuldt K, Förster B, Thiel M, May J, Koch-Nolte F, Yáñez-Mó M, Sánchez-Madrid F, Schinkel AH, Jalkanen S, Craig AG, Bruchhaus I, Horstmann RD.
Cell Microbiol. 2014 May;16(5):701-8. doi: 10.1111/cmi.12270. Epub 2014 Feb 24.

Evolution and transmission of drug-resistant tuberculosis in a Russian population.
Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O, Kontsevaya I, Corander J, Bryant J, Parkhill J, Nejentsev S, Horstmann RD, Brown T, Drobniewski F.
Nat Genet. 2014 Mar;46(3):279-86. doi: 10.1038/ng.2878. Epub 2014 Jan 26

Endothelial protein C receptor gene variants not associated with severe malaria in Ghanaian children.
Schuldt K, Ehmen C, Evans J, May J, Ansong D, Sievertsen J, Muntau B, Ruge G, Agbenyega T, Horstmann RD.
PLoS One. 2014 Dec 26;9(12):e115770. doi: 10.1371/journal.pone.0115770. eCollection 2014.

Host genetic studies in adult pulmonary tuberculosis.
Meyer CG, Thye T.
Semin Immunol. 2014 Dec;26(6):445-53. doi: 10.1016/j.smim.2014.09.005. Epub 2014 Oct 11. Review.

Polymorphism in NFKBIA gene is associated with recurrent acute rejections in liver transplant recipients.
Kramer K, Thye T, Treszl A, Peine S, Koch M, Sterneck M, Nashan B, Thude H.
Tissue Antigens. 2014 Oct;84(4):370-7. doi: 10.1111/tan.12411. Epub 2014 Aug 11.

Suspected new wave of muscular sarcocystosis in travellers returning from Tioman Island, Malaysia, May 2014.
Tappe D, Stich A, Langeheinecke A, von Sonnenburg F, Muntau B, Schäfer J, Slesak G.
Euro Surveill. 2014 May 29;19(21). pii: 20816.

A case of autochthonous human Dirofilaria infection, Germany, March 2014.
Tappe D, Plauth M, Bauer T, Muntau B, Dießel L, Tannich E, Herrmann-Trost P.
Euro Surveill. 2014 May 1;19(17):2-4.

Travel-acquired subcutaneous Sparganum proliferum infection diagnosed by molecular methods.
Schauer F, Poppert S, Technau-Hafsi K, Mockenhaupt M, Muntau B, Häcker G, Tappe D, Jakob T.
Br J Dermatol. 2014 Mar;170(3):741-3. doi: 10.1111/bjd.12679. No abstract available.

The Eu's Migration and Development Policy: New Approaches in Economics for More Effective Public Aid
S. Mueller-Using, and H. Vöpel
Intereconomics 2014; 49:95-101

2013

The spectrum of β-thalassemia mutations in Gaza Strip, Palestine.
Sirdah MM, Sievertsen J, Al-Yazji MS, Tarazi IS, Al-Haddad RM, Horstmann RD, Timmann C.
Blood Cells Mol Dis. 2013 Apr;50(4):247-51. doi: 10.1016/j.bcmd.2012.12.004. Epub 2013 Jan 12.

Imputation-based meta-analysis of severe malaria in three African populations.
Band G, Le QS, Jostins L, Pirinen M, Kivinen K, Jallow M, Sisay-Joof F, Bojang K, Pinder M, Sirugo G, Conway DJ, Nyirongo V, Kachala D, Molyneux M, Taylor T, Ndila C, Peshu N, Marsh K, Williams TN, Alcock D, Andrews R, Edkins S, Gray E, Hubbart C, Jeffreys A, Rowlands K, Schuldt K, Clark TG, Small KS, Teo YY, Kwiatkowski DP, Rockett KA, Barrett JC, Spencer CC; Malaria Genomic Epidemiology Network.
PLoS Genet. 2013 May;9(5):e1003509. doi: 10.1371/journal.pgen.1003509. Epub 2013 May 23. Erratum in: PLoS Genet. 2013 Jun;9(6). doi:10.1371/annotation/adc2beaf-4bee-4e22-925b-6788d62fe029.

Human infection with marten tapeworm.
Eberwein P, Haeupler A, Kuepper F, Wagner D, Kern WV, Muntau B, Racz P, Agostini H, Poppert S.
Emerg Infect Dis. 2013 Jul;19(7):1152-4. doi: 10.3201/eid1907.121114.

Case report: Molecular diagnosis of subcutaneous Spirometra erinaceieuropaei sparganosis in a Japanese immigrant.
Tappe D, Berger L, Haeupler A, Muntau B, Racz P, Harder Y, Specht K, Prazeres da Costa C, Poppert S.
Am J Trop Med Hyg. 2013 Jan;88(1):198-202. doi: 10.4269/ajtmh.2012.12-0406. Epub 2012 Nov 19.

2012

Genome-wide association study indicates two novel resistance loci for severe malaria.
Timmann C, Thye T, Vens M, Evans J, May J, Ehmen C, Sievertsen J, Muntau B, Ruge G, Loag W, Ansong D, Antwi S, Asafo-Adjei E, Nguah SB, Kwakye KO, Akoto AO, Sylverken J, Brendel M, Schuldt K, Loley C, Franke A, Meyer CG, Agbenyega T, Ziegler A, Horstmann RD.
Nature. 2012 Sep 20;489(7416):443-6. doi: 10.1038/nature11334. Epub 2012 Aug 15.

Common variants at 11p13 are associated with susceptibility to tuberculosis.
Thye T, Owusu-Dabo E, Vannberg FO, van Crevel R, Curtis J, Sahiratmadja E, Balabanova Y, Ehmen C, Muntau B, Ruge G, Sievertsen J, Gyapong J, Nikolayevskyy V, Hill PC, Sirugo G, Drobniewski F, van de Vosse E, Newport M, Alisjahbana B, Nejentsev S, Ottenhoff TH, Hill AV, Horstmann RD, Meyer CG.
Nat Genet. 2012 Feb 5;44(3):257-9. doi: 10.1038/ng.1080.

Microevolution of extensively drug-resistant tuberculosis in Russia.
Casali N, Nikolayevskyy V, Balabanova Y, Ignatyeva O, Kontsevaya I, Harris SR, Bentley SD, Parkhill J, Nejentsev S, Hoffner SE, Horstmann RD, Brown T, Drobniewski F.
Genome Res. 2012 Apr;22(4):735-45. doi: 10.1101/gr.128678.111. Epub 2012 Jan 31.

Are insecticide treated bednets failing?
Meyer CG, Ehrhardt S.
Lancet Infect Dis. 2012 Jul;12(7):513-4; author reply 514. doi: 10.1016/S1473-3099(12)70106-8. No abstract available.

Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population.
Lainka E, Bielak M, Lohse P, Timmann C, Stojanov S, von Kries R, Niehues T, Neudorf U.
Eur J Pediatr. 2012 Dec;171(12):1775-85. doi: 10.1007/s00431-012-1803-8. Epub 2012 Aug 19.

Transfer of evidence-based medical guidelines to low- and middle-income countries.
Ehrhardt S, Meyer CG.
Trop Med Int Health. 2012 Feb;17(2):144-6. doi: 10.1111/j.1365-3156.2011.02910.x. Epub 2011 Oct 21. No abstract available.

MtDNA diversity of Ghana: a forensic and phylogeographic view.
Fendt L, Röck A, Zimmermann B, Bodner M, Thye T, Tschentscher F, Owusu-Dabo E, Göbel TM, Schneider PM, Parson W.
Forensic Sci Int Genet. 2012 Mar;6(2):244-9. doi: 10.1016/j.fsigen.2011.05.011. Epub 2011 Jun 30.

Human Dirofilaria repens Infection in Romania: A Case Report.
Popescu I, Tudose I, Racz P, Muntau B, Giurcaneanu C, Poppert S.
Case Rep Infect Dis. 2012;2012:472976. doi: 10.1155/2012/472976. Epub 2012 Feb 7.

Guidelines for the use and interpretation of assays for monitoring autophagy.
Klionsky DJ,...Meyer CG,...Zuckerbraun B.
Autophagy. 2012 Apr;8(4):445-544.

2011

Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis.
Thye T, Niemann S, Walter K, Homolka S, Intemann CD, Chinbuah MA, Enimil A, Gyapong J, Osei I, Owusu-Dabo E, Rüsch-Gerdes S, Horstmann RD, Ehlers S, Meyer CG.
PLoS One. 2011;6(6):e20908. doi: 10.1371/journal.pone.0020908. Epub 2011 Jun 10

IL3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks.
Meyer CG, Calixto Fernandes MH, Intemann CD, Kreuels B, Kobbe R, Kreuzberg C, Ayim M, Ruether A, Loag W, Ehmen C, Adjei S, Adjei O, Horstmann RD, May J.
Hum Mol Genet. 2011 Mar 15;20(6):1173-81. doi: 10.1093/hmg/ddq562. Epub 2011 Jan 10.

Susceptibility to tuberculosis is associated with TLR1 polymorphisms resulting in a lack of TLR1 cell surface expression.
Uciechowski P, Imhoff H, Lange C, Meyer CG, Browne EN, Kirsten DK, Schröder AK, Schaaf B, Al-Lahham A, Reinert RR, Reiling N, Haase H, Hatzmann A, Fleischer D, Heussen N, Kleines M, Rink L.
J Leukoc Biol. 2011 Aug;90(2):377-88. doi: 10.1189/jlb.0409233. Epub 2011 Jun 3.

MCP1 haplotypes associated with protection from pulmonary tuberculosis.
Intemann CD, Thye T, Förster B, Owusu-Dabo E, Gyapong J, Horstmann RD, Meyer CG.
BMC Genet. 2011 Apr 19;12:34. doi: 10.1186/1471-2156-12-34.

Neighborhood urban environmental quality conditions are likely to drive malaria and diarrhea mortality in Accra, Ghana.
Fobil JN, Kraemer A, Meyer CG, May J.
J Environ Public Health. 2011;2011:484010. doi: 10.1155/2011/484010. Epub 2011 Jun 21.

Abteilung Molekulare Medizin
2010

Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.
Thye T, Vannberg FO, Wong SH, Owusu-Dabo E, Osei I, Gyapong J, Sirugo G, Sisay-Joof F, Enimil A, Chinbuah MA, Floyd S, Warndorff DK, Sichali L, Malema S, Crampin AC, Ngwira B, Teo YY, Small K, Rockett K, Kwiatkowski D, Fine PE, Hill PC, Newport M, Lienhardt C, Adegbola RA, Corrah T, Ziegler A; African TB Genetics Consortium; Wellcome Trust Case Control Consortium, Morris AP, Meyer CG, Horstmann RD, Hill AV.
Nat Genet. 2010 Sep;42(9):739-41. doi: 10.1038/ng.639. Epub 2010 Aug 8. Erratum in: Nat Genet. 2011 Oct;43(10):1040.

FCGR2A functional genetic variant associated with susceptibility to severe malarial anaemia in Ghanaian children.
Schuldt K, Esser C, Evans J, May J, Timmann C, Ehmen C, Loag W, Ansong D, Ziegler A, Agbenyega T, Meyer CG, Horstmann RD.
J Med Genet. 2010 Jul;47(7):471-5. doi: 10.1136/jmg.2009.073643. Epub 2009 Dec 3.

Rare human IFNG variants.
Thye T, Ehmen C, Intemann CD, Chinbuah MA, Ziegler A, Horstmann RD, Meyer CG.
J Interferon Cytokine Res. 2010 Apr;30(4):219-22. doi: 10.1089/jir.2009.0042.

A functional haplotype in the 3'untranslated region of TNFRSF1B is associated with tuberculosis in two African populations.
Möller M, Flachsbart F, Till A, Thye T, Horstmann RD, Meyer CG, Osei I, van Helden PD, Hoal EG, Schreiber S, Nebel A, Franke A.
Am J Respir Crit Care Med. 2010 Feb 15;181(4):388-93. doi: 10.1164/rccm.200905-0678OC.

Unequal distribution of resistance-conferring mutations among Mycobacterium tuberculosis and Mycobacterium africanum strains from Ghana.
Homolka S, Meyer CG, Hillemann D, Owusu-Dabo E, Adjei O, Horstmann RD, Browne EN, Chinbuah A, Osei I, Gyapong J, Kubica T, Ruesch-Gerdes S, Niemann S.
Int J Med Microbiol. 2010 Nov;300(7):489-95. doi: 10.1016/j.ijmm.2010.04.019.

King Tutankhamun's family and demise.
Timmann C, Meyer CG.
JAMA. 2010 Jun 23;303(24):2473; author reply 2473-5. doi: 10.1001/jama.2010.822. No abstract available.

Systemic bacteraemia in children presenting with clinical pneumonia and the impact of non-typhoid salmonella (NTS).
Schwarz NG, Sarpong N, Hünger F, Marks F, Acquah SE, Agyekum A, Nkrumah B, Loag W, Hagen RM, Evans JA, Dekker D, Fobil JN, Meyer CG, May J, Adu-Sarkodie Y.
BMC Infect Dis. 2010 Nov 4;10:319. doi: 10.1186/1471-2334-10-319.

Typhoid fever among children, Ghana.
Marks F, Adu-Sarkodie Y, Hünger F, Sarpong N, Ekuban S, Agyekum A, Nkrumah B, Schwarz NG, Favorov MO, Meyer CG, May J.
Emerg Infect Dis. 2010 Nov;16(11):1796-7. doi: 10.3201/eid1611.100388. No abstract available.

Malaria, mummies, mutations: Tutankhamun's archaeological autopsy.
Timmann C, Meyer CG.
Trop Med Int Health. 2010 Nov;15(11):1278-80. doi: 10.1111/j.1365-3156.2010.02614.x.

Abteilung Molekulare Medizin
2009

Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains.
Intemann CD, Thye T, Niemann S, Browne EN, Amanua Chinbuah M, Enimil A, Gyapong J, Osei I, Owusu-Dabo E, Helm S, Rüsch-Gerdes S, Horstmann RD, Meyer CG.
PLoS Pathog. 2009 Sep;5(9):e1000577. doi: 10.1371/journal.ppat.1000577. Epub 2009 Sep 11.

Genome-wide and fine-resolution association analysis of malaria in West Africa.
Jallow M, ... Horstmann RD, ... Kwiatkowski DP; Wellcome Trust Case Control Consortium; Malaria Genomic Epidemiology Network.
Nat Genet. 2009 Jun;41(6):657-65. doi: 10.1038/ng.388. Epub 2009 May 24.

MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa.
Thye T, Nejentsev S, Intemann CD, Browne EN, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Zeitels LR, Herb F, Horstmann RD, Meyer CG.
Hum Mol Genet. 2009 Jan 15;18(2):381-8. doi: 10.1093/hmg/ddn352. Epub 2008 Oct 20.

IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB.
Thye T, Browne EN, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Brattig NW, Niemann S, Rüsch-Gerdes S, Horstmann RD, Meyer CG.
PLoS One. 2009;4(5):e5420. doi: 10.1371/journal.pone.0005420. Epub 2009 May 1.

CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population.
Thye T, Scarisbrick G, Browne EN, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Niemann S, Rüsch-Gerdes S, Meyer CG, Horstmann RD.
PLoS One. 2009 Jul 17;4(7):e6307. doi: 10.1371/journal.pone.0006307.

A structural variant of the human interferon-gamma gene.
Thye T, Intemann CD, Gyapong J, Horstmann RD, Meyer CG.
Tissue Antigens. 2009 Mar;73(3):287-8. doi: 10.1111/j.1399-0039.2008.01207.x.

Genotyping of IRGM tetranucleotide promoter oligorepeats by fluorescence resonance energy transfer.
Intemann CD, Thye T, Sievertsen J, Owusu-Dabo E, Horstmann RD, Meyer CG.
Biotechniques. 2009 Jan;46(1):58-60.

Incidence of TNFRSF1A mutations in German children: epidemiological, clinical and genetic characteristics.
Lainka E, Neudorf U, Lohse P, Timmann C, Stojanov S, Huss K, von Kries R, Niehues T.
Rheumatology (Oxford). 2009 Aug;48(8):987-91. doi: 10.1093/rheumatology/kep140. Epub 2009 Jun 18.

Allele frequencies of 11 X-chromosomal loci in a population sample from Ghana.
Poetsch M, El-Mostaqim D, Tschentscher F, Browne EN, Timmann C, Horstmann RD, von Wurmb-Schwark N.
Int J Legal Med. 2009 Jan;123(1):81-3. doi: 10.1007/s00414-008-0251-5. Epub 2008 Jul 8.

Artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria.
Ehrhardt S, Meyer CG.
Ther Clin Risk Manag. 2009;5:805-15. Epub 2009 Oct 12.

[Molecular diagnostics of hereditary fever syndromes. Familial Mediterranean fever (FMF), hyperimmunoglobulin D syndrome (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS: FCAS, MWS, N
Timmann C, Horstmann R.
Z Rheumatol. 2009 Nov;68(9):720-5. doi: 10.1007/s00393-009-0486-7. German.

Abteilung Molekulare Medizin
2008

Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations.
Nejentsev S, Thye T, Szeszko JS, Stevens H, Balabanova Y, Chinbuah AM, Hibberd M, van de Vosse E, Alisjahbana B, van Crevel R, Ottenhoff THM, Png E, Drobniewski F, Todd JA, Seielstad M, Horstmann RD.
Nat Genet. 2008 Mar;40(3):261-2; author reply 262-3. doi: 10.1038/ng0308-261.

The Malaria Genomic Epidemiology Network. A global network for investigating the genomic epidemiology of malaria.

Nature. 2008 Dec 11;456(7223):732-7. doi: 10.1038/nature07632.

ALOX5 variants associated with susceptibility to pulmonary tuberculosis.
Herb F, Thye T, Niemann S, Browne ENL, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Werz O, Rüsch-Gerdes S, Horstmann RD, Meyer CG.
Hum Mol Genet. 2008 Apr 1;17(7):1052-60. doi: 10.1093/hmg/ddm378. Epub 2008 Jan 3.

Human Genetic Resistance to Onchocerca volvulus: Evidence for Linkage to Chromosome 2p from an Autosome-Wide Scan.
Timmann C, van der Kamp E, Kleensang A, König IR, Thye T, Büttner DW, Hamelmann C, Marfo Y, Vens M, Brattig N, Ziegler A, Horstmann RD.
J Infect Dis. 2008 Aug 1;198(3):427-33. doi: 10.1086/589720.

Pulmonary tuberculosis: virulence of Mycobacterium africanum and relevance in HIV co-infection.
Meyer CG, Scarisbrick G, Niemann S, Browne EN, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Kubica T, Rüsch-Gerdes S, Thye T, Horstmann RD.
Tuberculosis (Edinb). 2008 Sep;88(5):482-9. doi: 10.1016/j.tube.2008.05.004. Epub 2008 Jun 30.

Abteilung Molekulare Medizin
2007

Genome-wide linkage analysis of malaria infection intensity and mild disease.
Timmann C, Evans JA, König IR, Kleensang A, Rüschendorf F, Lenzen J, Sievertsen J, Becker C, Enuameh Y, Osei Kwakye K, Opoku E, Browne ENL, Ziegler A, Nürnberg P, Horstmann RD.
PLoS Genet. 2007 Mar 23;3(3):e48.

Hemoglobin variants and disease manifestations in severe falciparum malaria.
May J, Evans JA, Timmann C, Ehmen C, Busch W, Thye T, Agbenyega T, Horstmann RD.
JAMA. 2007 May 23;297(20):2220-6.

Chloroquine-resistant malaria in Malawi.
Kobbe R, Meyer CG, May J.
N Engl J Med. 2007 Feb 22;356(8):868; author reply 869. No abstract available.

A randomized controlled trial of extended intermittent preventive antimalarial treatment in infants.
Kobbe R, Kreuzberg C, Adjei S, Thompson B, Langefeld I, Thompson PA, Abruquah HH, Kreuels B, Ayim M, Busch W, Marks F, Amoah K, Opoku E, Meyer CG, Adjei O, May J.
Clin Infect Dis. 2007 Jul 1;45(1):16-25. Epub 2007 May 29.

Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi).
Kobbe R, Adjei S, Kreuzberg C, Kreuels B, Thompson B, Thompson PA, Marks F, Busch W, Tosun M, Schreiber N, Opoku E, Adjei O, Meyer CG, May J.
Malar J. 2007 Dec 9;6:163.

Abteilung Molekulare Medizin
2006

Capillary refill time as an independent prognostic indicator in severe and complicated malaria.
Evans JA, May J, Ansong D, Antwi S, Asafo-Adjei E, Blay Nguah S, Osei-Kwakye K, Osei Yaw Akoto A, Owusu Ofori A, Sambian D, Sylverken J, Busch W, Timmann C, Agbenyega T, Horstmann RD.
J Pediatr. 2006 Nov;149(5):676-81.

No associations of human pulmonary tuberculosis with Sp110 variants.
Thye T, Browne EN, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Niemann S, Rüsch-Gerdes S, Horstmann RD, Meyer CG.
J Med Genet. 2006 Jul;43(7):e32.

Mycobacterium tuberculosis drug resistance, Ghana.
Owusu-Dabo E, Adjei O, Meyer CG, Horstmann RD, Enimil A, Kruppa TF, Bonsu F, Browne EN, Chinbuah MA, Osei I, Gyapong J, Berberich C, Kubica T, Niemann S, Ruesch-Gerdes S.
Emerg Infect Dis. 2006 Jul;12(7):1171-2. No abstract available.

YAC/BAC contig spanning the MHC class III region of cattle.
Gelhaus A, Hess M, Förster B, Goldammer T, Schwerin M, Horstmann RD.
Cytogenet Genome Res. 2006;115(1):45-50.

Promoter polymorphism of the anion-exchange protein 1 associated with severe malarial anemia and fatality.
von Kalckreuth V, Evans JA, Timmann C, Kuhn D, Agbenyega T, Horstmann RD, May J.
J Infect Dis. 2006 Oct 1;194(7):949-57. Epub 2006 Aug 30.

Cerebral malaria is associated with IgG2 and IgG4 antibody responses to recombinant Plasmodium falciparum RIFIN antigen.
Schreiber N, Brattig N, Evans J, Tsiri Agbenyega, Horstmann RD, May J, Klinkert MQ.
Microbes Infect. 2006 Apr;8(5):1269-76. Epub 2006 Feb 6.

Hereditary periodic fever with systemic amyloidosis: is hyper-IgD syndrome really a benign disease?
Siewert R, Ferber J, Horstmann RD, Specker C, Heering PJ, Timmann C.
Am J Kidney Dis. 2006 Sep;48(3):e41-5.

Seasonal variation and high multiplicity of first Plasmodium falciparum infections in children from a holoendemic area in Ghana, West Africa.
Kobbe R, Neuhoff R, Marks F, Adjei S, Langefeld I, von Reden C, Adjei O, Meyer CG, May J.
Trop Med Int Health. 2006 May;11(5):613-9.

Abteilung Molekulare Medizin
2005

Relevance of ex vivo blood lymphocyte assay for in vivo lymphocyte function.
Brattig NW, Timmann C, Abraha RS, Lepping B, Müller-Myhsok B, Horstmann RD.
Clin Exp Immunol. 2005 Jan;139(1):127-31.

Novel TMC1 structural and splice variants associated with congenital nonsyndromic deafness in a Sudanese pedigree.
Meyer CG, Gasmelseed NM, Mergani A, Magzoub MM, Muntau B, Thye T, Horstmann RD.
Hum Mutat. 2005 Jan;25(1):100.

Rebound effects and emergence of Plasmodium falciparum pyrimethamine resistance by single dose sulfadoxine-pyrimethamine.
Marks F, von Kalckreuth V, Kobbe R, Adjei S, Adjei O, Horstmann RD, Meyer CG, May J.
J Infect Dis. 2005 Dec 1;192(11):1962-5. Epub 2005 Oct 20.

Diagnosis of alpha+-thalassemias by determining the ratio of the two alpha-globin gene copies by oligonucleotide hybridization and melting curve analysis.
Timmann C, Moenkemeyer F, Evans J, Foerster B, Tannich E, Haase S, Sievertsen J, Kohne E, Horstmann RD.
Clin Chem. 2005 Sep;51(9):1711-3.

High prevalence of markers for sulfadoxine and pyrimethamine resistance in Plasmodium falciparum in the absence of drug pressure in the Ashanti region of Ghana.
Marks F, Evans J, Meyer CG, Browne EN, Flessner C, von Kalckreuth V, Eggelte TA, Horstmann RD, May J.
Antimicrob Agents Chemother. 2005 Mar;49(3):1101-5.

Pre-treatment with chloroquine and parasite chloroquine resistance in Ghanaian children with severe malaria.
Evans JA, May J, Tominski D, Eggelte T, Marks F, Abruquah HH, Meyer CG, Timmann C, Agbenyega T, Horstmann RD.
QJM. 2005 Nov;98(11):789-96. Epub 2005 Sep 26.

2004

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen.
Timmann C, Fuchs S, Thoma C, Lepping B, Brattig NW, Sievertsen J, Thye T, Müller-Myhsok B, Horstmann RD.
Genes Immun. 2004 Jun;5(4):256-60.

High mortality of infant bacteraemia clinically indistinguishable from severe malaria.
Evans JA, Adusei A, Timmann C, May J, Mack D, Agbenyega T, Horstmann RD, Frimpong E.
QJM. 2004 Sep;97(9):591-7.

The species Mycobacterium africanum in the light of new molecular markers.
Niemann S, Kubica T, Bange FC, Adjei O, Browne EN, Chinbuah MA, Diel R, Gyapong J, Horstmann RD, Joloba ML, Meyer CG, Mugerwa RD, Okwera A, Osei I, Owusu-Darbo E, Schwander SK, Rüsch-Gerdes S.
J Clin Microbiol. 2004 Sep;42(9):3958-62.

Genotyping of Plasmodium falciparum pyrimethamine resistance by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.
Marks F, Meyer CG, Sievertsen J, Timmann C, Evans J, Horstmann RD, May J.
Antimicrob Agents Chemother. 2004 Feb;48(2):466-72.

Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants.
Gasmelseed NM, Schmidt M, Magzoub MM, Macharia M, Elmustafa OM, Ototo B, Winkler E, Ruge G, Horstmann RD, Meyer CG.
Hum Mutat. 2004 Feb;23(2):206-7.

Editorial: Gin tonic revisited.
Meyer CG, Marks F, May J.
Trop Med Int Health. 2004 Dec;9(12):1239-40. No abstract available.



Contact

Prof. Rolf Horstmann, MD

Phone: +49 40 42818-261
Fax: +49 40 42818-265
E-Mail: horstmann@bnitm.de


Secretary

Britta Rehn (-260)

Scientific Staff

Thorsten Thye, MD (-208)
Christian Timmann, MD (-516)
Christina Strauß (-534)

Technical Staff

Birgit Förster (-509)
Christa Ehmen (-514)
Britta Liedigk (-514)
Birgit Muntau (-514)
Gerd Ruge (-507)
Jürgen Sievertsen (-509)

Associated Scientist

Norbert W. Brattig, PhD (-530)

Laborgruppen

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