TY  - GEN
A1  - Volckmar, Anna-Lena
A1  - Han, Chung-Ting
A1  - Pütter, Carolin
A1  - Haas, Stefan
A1  - Vogel, Carla I. G.
A1  - Knoll, Nadja
A1  - Struve, Christoph
A1  - Göbel, Maria
A1  - Haas, Katharina
A1  - Herrfurth, Nikolas
A1  - Jarick, Ivonne
A1  - Grallert, Harald
A1  - Schürmann, Annette
A1  - Al- Hasani, Hadi
A1  - Hebebrand, Johannes
A1  - Sauer, Sascha
A1  - Hinney, Anke
T1  - Analysis of genes involved in body weight regulation by targeted re-sequencing
T2  - PLoS ONE
N2  - Introduction

Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing.

Methods

We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >= 99th percentile and 176 lean adults (BMI <= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults.

Results and Conclusion

We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (p(TDT) = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 423 
KW  - melanocortin-4 receptor gene
KW  - stimulated glucose-uptake
KW  - life-style intervention
KW  - onset extreme obesity
KW  - genome-wide analysis
KW  - mass index
KW  - FTO gene
KW  - fat mass
KW  - overweight children
KW  - diabetes-melllitus
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-410289
ER  - 
TY  - JOUR
A1  - Zirafi, Onofrio
A1  - Kim, Kyeong-Ae
A1  - Ständker, Ludger
A1  - Mohr, Katharina B.
A1  - Sauter, Daniel
A1  - Heigele, Anke
A1  - Kluge, Silvia F.
A1  - Wiercinska, Eliza
A1  - Chudziak, Doreen
A1  - Richter, Rudolf
A1  - Möpps, Barbara
A1  - Gierschik, Peter
A1  - Vas, Virag
A1  - Geiger, Hartmut
A1  - Lamla, Markus
A1  - Weil, Tanja
A1  - Burster, Timo
A1  - Zgraja, Andreas
A1  - Daubeuf, Francois
A1  - Frossard, Nelly
A1  - Hachet-Haas, Muriel
A1  - Heunisch, Fabian
A1  - Reichetzeder, Christoph
A1  - Galzi, Jean-Luc
A1  - Perez-Castells, Javier
A1  - Canales-Mayordomo, Angeles
A1  - Jimenez-Barbero, Jesus
A1  - Gimenez-Gallego, Guillermo
A1  - Schneider, Marion
A1  - Shorter, James
A1  - Telenti, Amalio
A1  - Hocher, Berthold
A1  - Forssmann, Wolf-Georg
A1  - Bonig, Halvard
A1  - Kirchhoff, Frank
A1  - Münch, Jan
T1  - Discovery and Characterization of an Endogenous CXCR4 Antagonist
JF  - Cell reports
N2  - CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Y1  - 2015
U6  - https://doi.org/10.1016/j.celrep.2015.03.061
SN  - 2211-1247
VL  - 11
IS  - 5
SP  - 737
EP  - 747
PB  - Cell Press
CY  - Cambridge
ER  -