Using antibodies raised against the unique N-terminus of each variant, we determined that PDE4D5, PDE4D8, and PDE4D9 are the splicing variants most abundant in cardiomyocytes, with trace amounts of PDE4D3.
Given the predicted pathogenicity of this variant, we determined whether it was also present in Proband N. Pyrosequencing across the c.1164del1 site showed this variant was not present in constitutional DNA from this individual (Supp. Fig. S5A).
Using a set of finite element (FE) model variants, we determined the mechanical stresses in muscle, fat, and skin tissues under the ischial tuberosities during sitting.
For the promoter variants, we determined nucleotide conservation across several species, performed transcription factor binding site (TFBS) analyses, and determined transmission and segregation patterns in families (Table S3 and Table S7).
To compare the catalytic efficiencies of the LC variants, we determined their substrate concentration at half maximal velocity, Km, and catalytic rate constant, kcat, from double reciprocal, Lineweaver-Burke plots (Figure 7).
To further investigate the putative function of these variants, we determined the overlap between SNVs and known histone marks in lymphoid cells (Supp. Table S9).
Considering that patients with schizophrenia were more likely to express ESR1 splice variants, we determined if they could have a functional impact on wild-type ESR1 signaling.
As a measure of MHC diversity besides the pure number of allelic variants, we determined allele divergence, i.e. the average genetic distance between all MHC IIB alleles of an individual.
From the remaining six plausible mtDNA variants, we determined whether they were causative using the following inclusion criteria for further analysis: (1) cells were viable for further assay, (2) mtDNA variants corresponded to the enzyme assay data in the RC subunit, (3) enzyme deficiency was observed in the fibroblasts, and (4) variants had high heteroplasmy ratios (Fig. 1 and Table 2).
To evaluate the efficiency and fidelity in Mn2+-dependent nucleotide insertion opposite G and DNA lesions by six pol ι variants, we determined steady-state kinetic parameters for nucleotide incorporation opposite a G or each of four lesions in the presence of 0.15 mM MnCl2 by six variants in comparison to the wild-type (Tables 5– 7).
Unfortunately, we are unable to report the structure of the F55Y variant, but we determined the structure of F55W to 1.9 Å resolution (Table S3 of the Supporting Information).
