TY  - JOUR
A1  - Förster, Daniel W.
A1  - Bull, James K.
A1  - Lenz, Dorina
A1  - Autenrieth, Marijke
A1  - Paijmans, Johanna L. A.
A1  - Kraus, Robert H. S.
A1  - Nowak, Carsten
A1  - Bayerl, Helmut
A1  - Kühn, Ralph
A1  - Saveljev, Alexander P.
A1  - Sindicic, Magda
A1  - Hofreiter, Michael
A1  - Schmidt, Krzysztof
A1  - Fickel, Jörns
T1  - Targeted resequencing of coding DNA sequences for SNP discovery in nonmodel species
JF  - Molecular ecology resources
N2  - Targeted capture coupled with high-throughput sequencing can be used to gain information about nuclear sequence variation at hundreds to thousands of loci. Divergent reference capture makes use of molecular data of one species to enrich target loci in other (related) species. This is particularly valuable for nonmodel organisms, for which often no a priori knowledge exists regarding these loci. Here, we have used targeted capture to obtain data for 809 nuclear coding DNA sequences (CDS) in a nonmodel organism, the Eurasian lynx Lynx lynx, using baits designed with the help of the published genome of a related model organism (the domestic cat Felis catus). Using this approach, we were able to survey intraspecific variation at hundreds of nuclear loci in L. lynx across the species’ European range. A large set of biallelic candidate SNPs was then evaluated using a high-throughput SNP genotyping platform (Fluidigm), which we then reduced to a final 96 SNP-panel based on assay performance and reliability; validation was carried out with 100 additional Eurasian lynx samples not included in the SNP discovery phase. The 96 SNP-panel developed from CDS performed very successfully in the identification of individuals and in population genetic structure inference (including the assignment of individuals to their source population). In keeping with recent studies, our results show that genic SNPs can be valuable for genetic monitoring of wildlife species.
KW  - CDS
KW  - conservation genetics
KW  - Eurasian lynx
KW  - genetic monitoring
KW  - hybridization capture
KW  - single nucleotide polymorphism
Y1  - 2018
U6  - https://doi.org/10.1111/1755-0998.12924
SN  - 1755-098X
SN  - 1755-0998
VL  - 18
IS  - 6
SP  - 1356
EP  - 1373
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Mota, Cristiano
A1  - Esmaeeli Moghaddam Tabalvandani, Mariam
A1  - Coelho, Catarina
A1  - Santos-Silva, Teresa
A1  - Wolff, Martin
A1  - Foti, Alessandro
A1  - Leimkühler, Silke
A1  - Romao, Maria Joao
T1  - Human aldehyde oxidase (hAOX1)
BT  - structure determination of the Moco-free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms
JF  - FEBS Open Bio
N2  - Human aldehyde oxidase (hAOX1) is a molybdenum enzyme with high toxicological importance, but its physiological role is still unknown. hAOX1 metabolizes different classes of xenobiotics and is one of the main drug-metabolizing enzymes in the liver, along with cytochrome P450. hAOX1 oxidizes and inactivates a large number of drug molecules and has been responsible for the failure of several phase I clinical trials. The interindividual variability of drug-metabolizing enzymes caused by single nucleotide polymorphisms (SNPs) is highly relevant in pharmaceutical treatments. In this study, we present the crystal structure of the inactive variant G1269R, revealing the first structure of a molybdenum cofactor (Moco)-free form of hAOX1. These data allowed to model, for the first time, the flexible Gate 1 that controls access to the active site. Furthermore, we inspected the thermostability of wild-type hAOX1 and hAOX1 with various SNPs (L438V, R1231H, G1269R or S1271L) by CD spectroscopy and ThermoFAD, revealing that amino acid exchanges close to the Moco site can impact protein stability up to 10 degrees C. These results correlated with biochemical and structural data and enhance our understanding of hAOX1 and the effect of SNPs in the gene encoding this enzyme in the human population. EnzymesAldehyde oxidase (); xanthine dehydrogenase (); xanthine oxidase (). DatabasesStructural data are available in the Protein Data Bank under the accession number .
KW  - human aldehyde oxidase
KW  - molybdenum cofactor
KW  - single nucleotide polymorphism
KW  - xanthine oxidase
Y1  - 2019
U6  - https://doi.org/10.1002/2211-5463.12617
SN  - 2211-5463
VL  - 9
IS  - 5
SP  - 925
EP  - 934
PB  - Wiley
CY  - Hoboken
ER  -