Homo sapiens
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PROVIDER: PRJNA305894 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Disease Variant Landscape of a Large Multi-Ethnic Population of Moyamoya Patients by Exome Sequencing
| PRJNA493158 | ENA
Project description:Disease Variant Landscape of a Large Multi-Ethnic Population of Moyamoya Patients by Exome Sequencing
| PRJNA493157 | ENA
Project description:Genomic Variations in a Multi-Ethnic Population in Malaysia
| PRJNA221114 | ENA
Project description:Genomic Variations in a Multi-Ethnic Population in Malaysia
| PRJNA221113 | ENA
Project description:Background: Moyamoya is a cerebrovascular condition of unknown mechanism characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the compensatory development of abnormal “moyamoya” vessels. It leads to ischemic and hemorrhagic stroke. We describe a novel autosomal recessive disease leading to severe moyamoya and early onset achalasia and report its cause in 3 unrelated families. Methods: We used a combination of genetic linkage and exome sequencing in 2 consanguineous to identify rare shared variants. Sanger sequencing of GUCY1A3, the sole gene mutated in both families, was then conducted in the third family. Platelets from one of the patients and controls were used to carry out functional studies. Results: Homozygous mutations of GUCY1A3 gene encoding the alpha1 subunit of soluble guanylate cyclase (sGC), the major receptor for Nitric Oxide (NO), were identified in all 3 families. Platelet analysis showed a complete loss of the mutated protein and showed an unexpected stimulatory role of sGC within platelets. Conclusion: The NO/sGC/cGMP pathway is a major pathway controlling vascular smooth muscle (VSMC) relaxation, vascular tone and vascular remodeling. Our data suggest that alterations of this pathway may lead to an abnormal vascular remodeling process in sensitive vascular areas with low blood A total of 17 samples (8 affected and 9 unaffected) were used for this study. Linkage analysis was performed in a single informative consanguine family composed of 2 unaffected parents, 4 affected siblings and 3 unaffected siblings. Two affected samples in two different families were used for the exome sequencing analysis and results were compared to 20 control exomes (in-house exomes from IntegraGen, Evry, France) and 8 HapMap exomes. All samples were used for Sanger Sequencing confirmation.
2014-06-19 | E-GEOD-48099 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
| S-EPMC4686780 | biostudies-literature
Project description:PurposeWe investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level.MethodsSNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively.ResultsSix of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes.ConclusionsThere is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.
| S-EPMC3743458 | biostudies-literature