Finally, we have performed detergent free staining of S2R+ cells expressing each receptor variant and observe robust surface localization.
We also detected new Ty1 variants, and observed that the repertoires of subfamilies corresponding to the closely related Ty1 and Ty2 elements differ from one strain to another.
We constructed these variants and observed a relatively small, 10-fold rate deceleration for the P78G mutant relative to that of the wild type (Table 1).
However, we tested the deactivation kinetics of the two mouse splice variants and observed no change in the activation or deactivation kinetics.
In addition, we assayed the protein localization and expression levels of Robo2 and its deletion variants and observed comparable surface expression in cultured S2R+ cells in vitro, as well as comparable expression levels and localization in CNS axons in vivo.
To further test precision of our combined method, we ran our combined model on the whole plasma dataset (expected to contain no large de novo variants) and observed the number of CNV calls for each size.
They honed in on a set of putative causal variants and observed that variants that were associated with most autoimmune diseases were specifically enriched in active chromatin from T cells, whereas variants that were associated with lupus were most enriched in active chromatin from B cells, T cells, and monocytes.
We therefore successively reduced the sequence coverage in the raw exome data of NA06986, called variants anew, and observed an increasing distance to the reference set (green to blue circle in Figure 3).
For comparison, we also performed similar experiments in the SUR1 A1369 T2D susceptibility variant [ 2] and observed that diazoxide was still able to increase KATP current further in the presence of GTP (3.19±0.10 compared with 2.87±0.07; P<0.05; Figures 7C and 7D).
CYP3A4 activity is known to display broad interindividual variability and, in contrast to other drug-metabolizing CYP enzymes, convincing associations between variant CYP3A4 alleles and observed in vivo enzymatic activity are lacking (32).
