Disease Variant Landscape of a Large Multi-Ethnic Population of Moyamoya Patients by Exome Sequencing
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PROVIDER: PRJNA493157 | ENA |
REPOSITORIES: ENA
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Project description:Disease Variant Landscape of a Large Multi-Ethnic Population of Moyamoya Patients by Exome Sequencing
| PRJNA493158 | ENA
Project description:Moyamoya disease is a rare cerebrovascular disorder characterized by progressive stenosis of large intracranial arteries and a secondary compensatory network of vulnerable collaterals. While the underlying molecular mechanisms remain unclear, both genetic and immune factors have been implicated, calling for a multiomics approach to study the complex pathogenesis of the disease. We performed whole exosome sequencing and plasma proteomics on a cohort of twelve patients with well-documented moyamoya angiopathy. In addition, we conducted an in-depth single cell spatial proteomics analysis on an occluded artery retrieved post-mortem from one idiopathic patient. Variants in the major susceptibility gene RNF213 were found in three patients, while five patients had other underlying genetic conditions, including trisomy 21 and pathogenic variants in ACTA2, SAMHD1 and NFIA. Plasma proteomics revealed cellular fibronectin as a potential biomarker for moyamoya disease, while artery spatial proteomics profiling showed extensive vascular smooth muscle cell infiltration in the intima associated with phenotypic switching. Moreover, infiltration of macrophages and antigen-presenting cells points to a role for inflammatory signals in disease progression. Together, our study supports a multiomics approach to unravel the complex pathogenesis of moyamoya disease, demonstrating the relevance of genetic and immune triggers in vascular remodeling and moyamoya disease development.
2025-10-20 | PXD063236 | Pride
Project description:Common and rare variant prediction and penetrance of IBD in a large, multi-ethnic, health system-based biobank cohort
| PRJNA632621 | ENA
Project description:The Malaysian Node of the Human Variome Project Database (MyHVPDb) is a country specific database of human variant and gene mutation that was established in 2011. This ethnic specific mutation and variation databases are being continuously updated, recording extensive information over the genetic heterogeneity of the Malaysian ethnic groups. The database comprises of SNP Database and Mutation Database. The SNP database has stored 291718 SNPs that was obtained by genotyping the SNPs of 101 healthy individuals from six Malay sub-ethnic groups which consist of Malay Kelantan, Malay Banjar, Malay Kedah, Malay Jawa, Malay Bugis and Malay Champa.
2015-02-11 | GSE65760 | GEO
Project description:The Malaysian Node of the Human Variome Project Database (MyHVPDb) is a country specific database of human variant and gene mutation that was established in 2011. This ethnic specific mutation and variation databases are being continuously updated, recording extensive information over the genetic heterogeneity of the Malaysian ethnic groups. The database comprises of SNP Database and Mutation Database. The SNP database has stored 291718 SNPs that was obtained by genotyping the SNPs of 101 healthy individuals from six Malay sub-ethnic groups which consist of Malay Kelantan, Malay Banjar, Malay Kedah, Malay Jawa, Malay Bugis and Malay Champa. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from blood samples.
2015-02-11 | E-GEOD-65760 | biostudies-arrayexpress
Project description:We performed microarray analysis to determine the expression profiles of miRNAs in cerebrospinal fluid with moyamoya disease
2020-04-03 | GSE129792 | GEO
Project description:Exome Sequencing of a Large Multi-Ethnic Population of Moyamoya Patients
| PRJNA305894 | ENA
Project description:Moyamoya disease (MMD) is a rare and progressive cerebrovascular disorder characterized by the gradual stenosis (narrowing) and occlusion of critical intracranial arteries. The etiology of this disease is still unknown. Here we use Laser capture microdissection followed by shotgun proteomics to analyse the brain of a moyamoya patient. We found that phenotypic switching of VSMCs may be involved in the occlusion of the arteries. In addition, invasion of immune cells such as macrophages, in the occluding tissue were found, strengthening the hypothesis that an abberant immune response to infection may be one of the key mechanisms in MMD pathology.
2025-10-20 | PXD057183 | Pride
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:Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (~30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells (PBMCs) from African-American and European-American healthy donors. We found that transcriptional response after 8hrs treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly downregulated in European-Americans on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (FDR<0.05), most of which also showed a weaker transcriptional response in AfricanAmericans. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (e.g. NFKB1) and numerous other genes with smaller effects.
2012-02-01 | GSE33649 | GEO