Dataset Information

Data on solute carrier transporter genes of a threatened Himalayan fish species - Schizothorax richardsonii.

ABSTRACT: The Snowtrout, Schizothorax richardsonii, is a vulnerable fish species found in different rivers and rivulets of the Himalayan region. The species is also a suitable poikilotherm to study the low-temperature tolerance as it dwells well at a temperature range of 5-20 °C. The solute carrier (SLC) group of membrane transport proteins play an integral role in cellular acclimation response. The present RNA sequencing was done to identify solute carrier transporter which are the major gene cascades responsible for transport of sugars, amino acids, oligonucleotides, ions, drugs, etc. to and from the cell organelles. A reference transcriptome database was created from liver tissue of Schizothorax richardsonii through RNA sequencing on Illumina HiSeq 2000 platform. The sequences were annotated and characterized under various solute carrier families in the species. So far, 113 transcripts were identified as solute carrier transporter genes categorized under 13 different families. This data will be useful for many researchers working on gene cloning and differential expression of solute carriers.

SUBMITTER: Barat A

PROVIDER: S-EPMC6660431 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Data on solute carrier transporter genes of a threatened Himalayan fish species - <i>Schizothorax richardsonii</i>.

Barat Ashoktaru A Sahoo Prabhati Kumari PK Kumar Rohit R Goel Chirag C Siva C C Ali Shahnawaz S

Data in brief 20190307

The Snowtrout, <i>Schizothorax richardsonii</i>, is a vulnerable fish species found in different rivers and rivulets of the Himalayan region. The species is also a suitable poikilotherm to study the low-temperature tolerance as it dwells well at a temperature range of 5-20 °C. The solute carrier (SLC) group of membrane transport proteins play an integral role in cellular acclimation response. The present RNA sequencing was done to identify solute carrier transporter which are the major gene casc ...[more]

PMID: 31372384

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Project description:The human solute carrier (SLC) superfamily of transporters is comprised of over 400 membrane-bound proteins, and plays essential roles in a multitude of physiological and pharmacological processes. In addition, perturbation of SLC transporter function underlies numerous human diseases, which renders SLC transporters attractive drug targets. Common genetic polymorphisms in SLC genes have been associated with inter-individual differences in drug efficacy and toxicity. However, despite their tremendous clinical relevance, epidemiological data of these variants are mostly derived from heterogeneous cohorts of small sample size and the genetic SLC landscape beyond these common variants has not been comprehensively assessed. In this study, we analyzed Next-Generation Sequencing data from 141,456 individuals from seven major human populations to evaluate genetic variability, its functional consequences, and ethnogeographic patterns across the entire SLC superfamily of transporters. Importantly, of the 204,287 exonic single-nucleotide variants (SNVs) which we identified, 99.8% were present in less than 1% of analyzed alleles. Comprehensive computational analyses using 13 partially orthogonal algorithms that predict the functional impact of genetic variations based on sequence information, evolutionary conservation, structural considerations, and functional genomics data revealed that each individual genome harbors 29.7 variants with putative functional effects, of which rare variants account for 18%. Inter-ethnic variability was found to be extensive, and 83% of deleterious SLC variants were only identified in a single population. Interestingly, population-specific carrier frequencies of loss-of-function variants in SLC genes associated with recessive Mendelian disease recapitulated the ethnogeographic variation of the corresponding disorders, including cystinuria in Jewish individuals, type II citrullinemia in East Asians, and lysinuric protein intolerance in Finns, thus providing a powerful resource for clinical geneticists to inform about population-specific prevalence and allelic composition of Mendelian SLC diseases. In summary, we present the most comprehensive data set of SLC variability published to date, which can provide insights into inter-individual differences in SLC transporter function and guide the optimization of population-specific genotyping strategies in the bourgeoning fields of personalized medicine and precision public health.

Project description:Background & aimsBile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis.MethodsWe measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments with Slco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport.ResultsHepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet-induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in the SLCO3A1 promoter. Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids.ConclusionsWe found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.

Dataset Information

Data on solute carrier transporter genes of a threatened Himalayan fish species - Schizothorax richardsonii.

Publications

Data on solute carrier transporter genes of a threatened Himalayan fish species - <i>Schizothorax richardsonii</i>.

Similar Datasets

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