The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (SLC38A3, SLC38A7 and SLC38A9) Affects Susceptibility to Type 2 Diabetes and Vascular Complications

Crocco, Paolina; Dato, Serena; Montesanto, Alberto; Bonfigli, Anna Rita; Testa, Roberto; Olivieri, Fabiola; Passarino, Giuseppe; Rose, Giuseppina

doi:10.3390/nu14214440

Genomic landscape reveals evolutionary footprints of adaptability in Indian hill cattle

Ahmad

2023

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The present study is aimed to assess the population structure of hill cattle and analyze the genomic footprints of selection and adaptation. The population structure and signatures of selection were analyzed in hill cattle in comparison to Indian milch, non-milch and exotic cattle populations, using Illumina high-density genotyping data. The present study used high-density SNP genotyping data generated on Illumina BovineHD SNP BeadChip on a total of 299 individuals representing 14 bovine populations across three groups i.e., Hill cattle (Ladakhi and Siri), Indian milch cattle (Sahiwal, Gir, Tharparkar), Indian non-milch cattle (Hariana, Hallikar, Kankrej, Ongole, and Vecheur) and exotic group (Holstein-Friesian, Jersey, Brown Swiss and Guernsey). The grouping of populations was based on utility, inheritance and characteristics related to the terrain of breeding tract. The final merged dataset included coverage on 4,68,671 common autosomal SNP markers after quality pruning using different thresholds. The population structure was assessed using principal component analysis and maximum likelihood-based TreeMix analysis while twin methods (iHS, and XP-EHH) were used to scan the whole genome for haplotype homozygosity statistics. Multiple chromosomes were observed to harbour SNPs under selective sweeps in different comparisons. TRIM44, SLC5A12, MYO1D and NAPB were important genes that showed overlap with SNP markers whose frequency was significantly different than overall hill cattle genome under selection. Various genes were found as part of selection footprints along multiple comparisons including U6, ADGRL3, RELN, DAP3, STO1, DNAJA2. A functional analysis of the genes harbouring SNPs under evolutionary pressure (as part of selection sweeps) was undertaken to gain deeper insights into the biological relevance of selection footprints. The genes as part of selection sweeps were mainly involved in important adaptation traits including cell-cell signalling, neuronal development, mitochondrial functioning, hyaluronidase functioning, ion-channel transport of solute and nutrients, and response to reactive oxygen species and other stressors. The present study provides detailed insights into the genomic landscape changes that are result of adaptation of hill cattle to agro-climatic conditions under which they are reared.

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Genomic landscape reveals evolutionary footprints of adaptability in Indian hill cattle

Ahmad,

Aarif,

Kumar

et al. 2023

Preprint

0

View full text Add to dashboard Cite

The present study is aimed to assess the population structure of hill cattle and analyze the genomic footprints of selection and adaptation. The population structure and signatures of selection were analyzed in hill cattle in comparison to Indian milch, non-milch and exotic cattle populations, using Illumina high-density genotyping data. The present study used high-density SNP genotyping data generated on Illumina BovineHD SNP BeadChip on a total of 299 individuals representing 14 bovine populations across three groups i.e., Hill cattle (Ladakhi and Siri), Indian milch cattle (Sahiwal, Gir, Tharparkar), Indian non-milch cattle (Hariana, Hallikar, Kankrej, Ongole, and Vecheur) and exotic group (Holstein-Friesian, Jersey, Brown Swiss and Guernsey). The grouping of populations was based on utility, inheritance and characteristics related to the terrain of breeding tract. The final merged dataset included coverage on 4,68,671 common autosomal SNP markers after quality pruning using different thresholds. The population structure was assessed using principal component analysis and maximum likelihood-based TreeMix analysis while twin methods (iHS, and XP-EHH) were used to scan the whole genome for haplotype homozygosity statistics. Multiple chromosomes were observed to harbour SNPs under selective sweeps in different comparisons. TRIM44, SLC5A12, MYO1D and NAPB were important genes that showed overlap with SNP markers whose frequency was significantly different than overall hill cattle genome under selection. Various genes were found as part of selection footprints along multiple comparisons including U6, ADGRL3, RELN, DAP3, STO1, DNAJA2. A functional analysis of the genes harbouring SNPs under evolutionary pressure (as part of selection sweeps) was undertaken to gain deeper insights into the biological relevance of selection footprints. The genes as part of selection sweeps were mainly involved in important adaptation traits including cell-cell signalling, neuronal development, mitochondrial functioning, hyaluronidase functioning, ion-channel transport of solute and nutrients, and response to reactive oxygen species and other stressors. The present study provides detailed insights into the genomic landscape changes that are result of adaptation of hill cattle to agro-climatic conditions under which they are reared.

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The Role of the Nuclear Receptor FXR in Arsenic-Induced Glucose Intolerance in Mice

Yang,

Hsiao,

Liu

et al. 2023

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Inorganic arsenic in drinking water is prioritized as a top environmental contaminant by the World Health Organization, with over 230 million people potentially being exposed. Arsenic toxicity has been well documented and is associated with a plethora of human diseases, including diabetes, as established in numerous animal and epidemiological studies. Our previous study revealed that arsenic exposure leads to the inhibition of nuclear receptors, including LXR/RXR. To this end, FXR is a nuclear receptor central to glucose and lipid metabolism. However, limited studies are available for understanding arsenic exposure-FXR interactions. Herein, we report that FXR knockout mice developed more profound glucose intolerance than wild-type mice upon arsenic exposure, supporting the regulatory role of FXR in arsenic-induced glucose intolerance. We further exposed mice to arsenic and tested if GW4064, a FXR agonist, could improve glucose intolerance and dysregulation of hepatic proteins and serum metabolites. Our data showed arsenic-induced glucose intolerance was remarkably diminished by GW4064, accompanied by a significant ratio of alleviation of dysregulation in hepatic proteins (83%) and annotated serum metabolites (58%). In particular, hepatic proteins “rescued” from arsenic toxicity by GW4064 featured members of glucose and lipid utilization. For instance, the expression of PCK1, a candidate gene for diabetes and obesity that facilitates gluconeogenesis, was repressed under arsenic exposure in the liver, but revived with the GW4064 supplement. Together, our comprehensive dataset indicates FXR plays a key role and may serve as a potential therapeutic for arsenic-induced metabolic disorders.

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The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (SLC38A3, SLC38A7 and SLC38A9) Affects Susceptibility to Type 2 Diabetes and Vascular Complications

Cited by 3 publications

References 59 publications

Genomic landscape reveals evolutionary footprints of adaptability in Indian hill cattle

Genomic landscape reveals evolutionary footprints of adaptability in Indian hill cattle

Genomic landscape reveals evolutionary footprints of adaptability in Indian hill cattle

The Role of the Nuclear Receptor FXR in Arsenic-Induced Glucose Intolerance in Mice

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