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Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features of schizophrenia (SCZ) have been demonstrated in patients with several lysosomal storage disorders (LSDs). Taking into account the critical role of lysosomal function for neuronal cells’ lysosomal dysfunction could be proposed in SCZ pathogenesis. The current study analyzed lysosomal enzyme activities and the alpha-synuclein level in the blood of patients with late-onset SCZ. In total, 52 SCZ patients with late-onset SCZ, 180 sporadic Parkinson’s disease (sPD) patients, and 176 controls were recruited. The enzymatic activity of enzymes associated with mucopolysaccharidosis (alpha-L-Iduronidase (IDUA)), glycogenosis (acid alpha-glucosidase (GAA)) and sphingolipidosis (galactosylceramidase (GALC), glucocerebrosidase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase)) and concentration of lysosphingolipids (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), and lysosphingomyelin (LysoSM)) were measured using LC-MS/MS. The alpha-synuclein level was estimated in magnetically separated CD45+ blood cells using the enzyme-linked immunosorbent assay (ELISA). Additionally, NGS analysis of 11 LSDs genes was conducted in 21 early-onset SCZ patients and 23 controls using the gene panel PGRNseq-NDD. Decreased ASMase, increased GLA activities, and increased HexSpn, LysoGb3, and LysoSM concentrations along with an accumulation of the alpha-synuclein level were observed in late-onset SCZ patients in comparison to the controls (p < 0.05). Four rare deleterious variants among LSDs genes causing mucopolysaccharidosis type I (IDUA (rs532731688, rs74385837) and type III (HGSNAT (rs766835582)) and sphingolipidosis (metachromatic leukodystrophy (ARSA (rs201251634)) were identified in five patients from the group of early-onset SCZ patients but not in the controls. Our findings supported the role of sphingolipid metabolism in SCZ pathogenesis. Aberrant enzyme activities and compounds of sphingolipids associated with ceramide metabolism may lead to accumulation of alpha-synuclein and may be critical in SCZ pathogenesis.

Guar gum, a polysaccharide derived from guar seeds, is widely used in a variety of industrial applications, including oil and gas production. Although guar is mostly propagated in India, interest in guar as a new industrial legume crop is increasing worldwide, demanding the development of effective tools for marker-assisted selection. In this paper, we report a wide-ranging set of 4907 common SNPs and 327 InDels generated from RADseq genotyping data of 166 guar plants of different geographical origin. A custom guar reference genome was assembled and used for variant calling. A consensus set of variants was built using three bioinformatic pipelines for short variant discovery. The developed molecular markers were used for genome-wide association study, resulting in the discovery of six markers linked to the variation of an important agronomic trait—percentage of pods matured to the harvest date under long light day conditions. One of the associated variants was found inside the putative transcript sequence homologous to an ABC transporter in Arabidopsis, which has been shown to play an important role in D-myo-inositol phosphates metabolism. Earlier, we suggested that genes involved in myo-inositol phosphate metabolism have significant impact on the early flowering of guar plants. Hence, we believe that the developed SNP set allows for the identification of confident molecular markers of important agrobiological traits.

Background Next generation sequencing (NGS) has become a standard tool in the molecular diagnostics of Mendelian disease, and the precision of such diagnostics is greatly affected by the accuracy of variant calling from sequencing data. Recently, we have comprehensively evaluated the performance of multiple variant calling pipelines. However, no systematic analysis of the effects of read trimming on variant discovery with modern variant calling software has yet been performed. Methods In this work, we systematically evaluated the effects of adapters on the performance of 8 variant calling and filtering methods using 14 standard reference Genome-in-a-Bottle (GIAB) samples. Variant calls were compared to the ground truth variant sets, and the effect of adapter trimming with different tools was assessed using major performance metrics (precision, recall, and F1 score). Results We show that adapter trimming has no effect on the accuracy of the best-performing variant callers (e.g., DeepVariant) on whole-genome sequencing (WGS) data. For whole-exome sequencing (WES) datasets subtle improvement of accuracy was observed in some of the samples. In high-coverage WES data (~200x mean coverage), adapter removal allowed for discovery of 2-4 additional true positive variants in only two out of seven datasets tested. Moreover, this effect was not dependent on the median insert size and proportion of adapter sequences in reads. Surprisingly, the effect of trimming on variant calling was reversed when moderate coverage (~80-100x) WES data was used. Finally, we show that some of the recently developed machine learning-based variant callers demonstrate greater dependence on the presence of adapters in reads. Conclusions Taken together, our results indicate that adapter removal is unnecessary when calling germline variants, but suggest that preprocessing methods should be carefully chosen when developing and using machine learning-based variant analysis methods.