ZFIN ID: ZDB-LAB-120302-2
Neerman-Arbez Lab
PI/Director: Neerman-Arbez, Marguerite
Co-PI / Senior
Fish, Richard
Contact Person:
Email: Marguerite.Neerman-Arbez@unige.ch
URL: http://www.medecine.unige.ch/recherche/groupes/b_donnees/sujet_504_4.html
Address: Department of Genetic Medicine and Development University Medical Centre 1, rue Michel Servet Geneva 1211 Switzerland
Country: Switzerland
Phone: ++ 41 22 379 5655
Fax: ++ 41 22 379 5706
Line Designation: ug

Show all 2 genomic features

We are studying human genetic disorders of hemostasis, in particular fibrinogen deficiencies.
These are rare and affect either the quantity or the quality of circulating fibrinogen, which is the
precursor of the major protein component of the blood clot, fibrin. Our laboratory identified the
gene and the first causative mutations for complete deficiency of fibrinogen, afibrinogenemia, in
1999. Fibrinogen is a hexamer comprising two copies of three polypeptides. These are encoded
by the fibrinogen alpha, beta and gamma genes clustered on human chromosome 4. While still
pursuing studies of the molecular mechanisms by which fibrinogen gene mutations lead to
disease, we are also investigating the broader picture influencing fibrinogen levels (which are
highly variable amongst individuals), identifying new regulatory elements in the
genomic landscape of the fibrinogen cluster. We are also determining whether microRNAs are
involved in the fine-tuning of fibrinogen levels. Animal models i.e. the zebrafish (Danio rerio)
are used in the course of these projects. The discovery of novel mechanisms determining
fibrinogen levels in the circulation is clinically relevant since a high fibrinogen level is an
independent risk factor for cardiovascular disease.

Lukowski, Sam Post-Doc Vorjohann, Silja Graduate Student di Sanza, Corinne Technical Staff
Koegel, Jérémie

Neerman-Arbez, M., Casini, A. (2018) Clinical Consequences and Molecular Bases of Low Fibrinogen Levels. International Journal of Molecular Sciences. 19(1)
Gueneau, L., Fish, R.J., Shamseldin, H.E., Voisin, N., Tran Mau-Them, F., Preiksaitiene, E., Monroe, G.R., Lai, A., Putoux, A., Allias, F., Ambusaidi, Q., Ambrozaityte, L., Cimbalistienė, L., Delafontaine, J., Guex, N., Hashem, M., Kurdi, W., Jamuar, S.S., Ying, L.J., Bonnard, C., Pippucci, T., Pradervand, S., Roechert, B., van Hasselt, P.M., Wiederkehr, M., Wright, C.F., DDD Study, Xenarios, I., van Haaften, G., Shaw-Smith, C., Schindewolf, E.M., Neerman-Arbez, M., Sanlaville, D., Lesca, G., Guibaud, L., Reversade, B., Chelly, J., Kučinskas, V., Alkuraya, F.S., Reymond, A. (2017) KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis. American journal of human genetics. 102(1):116-132
Moysés-Oliveira, M., Giannuzzi, G., Fish, R.J., Rosenfeld, J.A., Petit, F., de Fatima Soares, M., Kulikowski, L.D., Battista, A.D., Zamariolli, M., Xia, F., Liehr, T., Kosyakova, N., Carvalheira, G., Parker, M., Seaby, E.G., Ennis, S., Gilbert, R.D., Hagelstrom, R.T., Cremona, M.L., Li, W.L., Malhotra, A., Chandrasekhar, A., Perry, D.L., Taft, R.J., McCarrier, J., Basel, D.G., Andrieux, J., Stumpp, T., Antunes, F., Pereira, G.J., Neerman-Arbez, M., Meloni, V.A., Drummond-Borg, M., Melaragno, M.I., Reymond, A. (2017) Inactivation of AMMECR1 is associated with growth, bone and heart alterations. Human Mutation. 39(2):281-291
Meta, E., Imhof, B.A., Ropraz, P., Fish, R.J., Brullo, C., Bruno, O., Sidibé, A. (2017) The pyrazolyl-urea GeGe3 inhibits tumor angiogenesis and reveals dystrophia myotonica protein kinase (DMPK)1 as a novel angiogenesis target. Oncotarget. 8:108195-108212
Lodder, E.M., De Nittis, P., Koopman, C.D., Wiszniewski, W., Moura de Souza, C.F., Lahrouchi, N., Guex, N., Napolioni, V., Tessadori, F., Beekman, L., Nannenberg, E.A., Boualla, L., Blom, N.A., de Graaff, W., Kamermans, M., Cocciadiferro, D., Malerba, N., Mandriani, B., Akdemir, Z.H., Fish, R.J., Eldomery, M.K., Ratbi, I., Wilde, A.A., de Boer, T., Simonds, W.F., Neerman-Arbez, M., Sutton, V.R., Kok, F., Lupski, J.R., Reymond, A., Bezzina, C.R., Bakkers, J., Merla, G. (2016) GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability. American journal of human genetics. 99(3):704-10
Popadin, K.Y., Gutierrez-Arcelus, M., Lappalainen, T., Buil, A., Steinberg, J., Nikolaev, S.I., Lukowski, S.W., Bazykin, G.A., Seplyarskiy, V.B., Ioannidis, P., Zdobnov, E.M., Dermitzakis, E.T., Antonarakis, S.E. (2014) Gene age predicts the strength of purifying selection acting on gene expression variation in humans. American journal of human genetics. 95:660-74
Bontems, F., Fish, R.J., Borlat, I., Lembo, F., Chocu, S., Chalmel, F., Borg, J.P., Pineau, C., Neerman-Arbez, M., Bairoch, A., and Lane, L. (2014) C2orf62 and TTC17 Are Involved in Actin Organization and Ciliogenesis in Zebrafish and Human. PLoS One. 9(1):e86476
Vorjohann, S., Pitetti, J.L., Nef, S., Gonelle-Gispert, C., Buhler, L., Fish, R.J., and Neerman-Arbez, M. (2013) DNA Methylation Profiling of the Fibrinogen Gene Landscape in Human Cells and during Mouse and Zebrafish Development. PLoS One. 8(8):e73089
Fish, R.J., and Neerman-Arbez, M. (2012) A novel regulatory element between the human FGA and FGG genes. Thrombosis and haemostasis. 108(3):427-434
Fish, R.J., Vorjohann, S., Béna, F., Fort, A., and Neerman-Arbez, M. (2012) Developmental expression and organisation of fibrinogen genes in the zebrafish. Thrombosis and haemostasis. 107(1):158-66