In the beginning was the mitochondrion

Here we propose a new theory about the cause of origin of Alzheimer's disease, taking into account recent progress in the field. Our hypothesis postulates the mitochondrial aging being the main cause of LOAD, and explains the connections between the cause and all the manifestations of the disease

Differential expression analysis results for <i>CEA (CEACAM5)</i> gene.

<p>a. Expression plot shows differences in the <i>CEACAM5</i> expression level between MIP101 (CEA-, blue color) and MIP101 clone 8 (CEA+, brown color) cell lines, measured in FPKM. Each sample was represented by two replicates. b. Expression level of <i>CEACAM5</i> is represented by single <i>CEACAM5-001</i> isoform.</p

The top 30 upregulated and downregulated genes in CEA+ and CEA- cells.

<p>The red color indicates upregulated mRNA; the blue color indicates downregulated mRNA. On the right side of the square are the names of the genes that differ in the expression between MIP101 (CEA-) and MIP101 clone 8 (CEA +) cell lines. The experiments were performed in two replicates starting from RNA extraction. As a control, we performed an analysis of the <i>CEA</i> gene and its isoforms expression level in these cell lines by RNA-seq data. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161256#pone.0161256.g002" target="_blank">Fig 2</a> shows plots of the <i>CEA</i> expression. Expression of the <i>CEA</i> gene is present in the CEA-producing line (MIP101 clone 8) and absent in the CEA-deficient cell line (MIP101). Moreover, CEA gene was represented by one isoform <i>CEACAM5-001</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161256#pone.0161256.g002" target="_blank">Fig 2B</a>).</p

Validation of RNA-Seq results was performed by qRT-PCR analysis on 5 randomly chosen genes from the list of differentially expressed genes.

<p>CEACAM5 also was analysed as positive control. Results obtained by RNA-Seq and qRT-PCR methods show high accordance. Each qRT-PCR was performed with three replicates. All data are means ± SD. (*p < 0.05; **p < 0.01, ***p < 0.001, one-way ANOVA for qRT-PCR and FDR-adjusted exact test for RNA-Seq).</p

<i>HLA-DRB1</i> and <i>FTCD</i> genotypes.

<p><i>HLA-DRB1</i> and <i>FTCD</i> genotypes.</p

Analytical “bake-off” of whole genome sequencing quality for the Genome Russia project using a small cohort for autoimmune hepatitis

<div><p>A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects. We assessed calling of SNPs, indels, copy number variation, and the speed of WGS throughput promised. Twenty separate QC analyses showed high similarities among the sequence quality and called genotypes. The ten genomes tested by the centers included eight American patients afflicted with autoimmune hepatitis (AIH), plus one case’s unaffected parents, in a prelude to discovering genetic influences in this rare disease of unknown etiology. The detailed internal replication and parallel analyses allowed the observation of two of eight AIH cases carrying a rare allele genotype for a previously described AIH-associated gene (<i>FTCD</i>), plus multiple occurrences of known <i>HLA-DRB1</i> alleles associated with AIH <i>(HLA-DRB1-03</i>:<i>01</i>:<i>01</i>, <i>13</i>:<i>01</i>:<i>01 and 7</i>:<i>01</i>:<i>01</i>). We also list putative SNVs in other genes as suggestive in AIH influence.</p></div

Raw read quality control parameters.

<p>Raw sequence read QC parameters are shown for three sequencing centers (colored differently).</p

Genotype comparison.

<p>(A) Concordance of WGS genotypes with microarray genotypes. The concordance was estimated based on the trio data as the ratio of microarray SNPs with identical genotypes in WGS results. (B) Comparison of the three WGS datasets between each other in terms of precision, sensitivity and F-measure for pairwise comparisons. Color legend is given on the top right. (C) Concordance of genotypes in the three WGS datasets for all variants, SNPs and indels. Color legend is given on the top right.</p

Sample description.

<p>Sample description.</p

Comparison of sequencing results (N = 17 parameters).

<p>Comparison of sequencing results (N = 17 parameters).</p