Scoop-G-1
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010001623 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:SCOOP severe early-onset obesity cases
| EGAD00010000594 | EGA
Project description:Obesity is considered a multifactorial disorder with high heritability (50-75%), probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including CNVs, have been defined, the genetic causes underlying the disease still remain largely unknown. We aimed to identify novel genetic and genomic abnormalities in a cohort of Spanish children with severe non-syndromic early-onset obesity (EOO). We obtained molecular karyotypes of 157 children with EOO. Large and rare CNVs were validated and segregated in the family. A higher burden of duplication-type CNVs was detected in EOO patients versus controls (OR=1.85, p-value=0.008).
2017-04-28 | E-MTAB-5680 | biostudies-arrayexpress
Project description:The variation in weight within a shared environment is largely attributable to genetic factors. Whilst many genes/loci confer susceptibility to obesity, little is known about the genetic architecture of thinness. In this study we performed a genome-wide association study of 1,622 persistently thin healthy individuals (STILTS), 1,985 severe childhood onset obesity cases (SCOOP) and 10,433 population based individuals (UKHLS) used as a common set of controls. All participants were genotyped on the Illumina Core Exome array, including 551,839 markers and imputed to the combined UK10K and 1000G (phase3) reference panel. We contrast the genetic architecture of thinness with that of severe early onset obesity and explore whether the genetic loci influencing thinness are the same as those influencing obesity pr whether there are important genetic differences between them.
This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing
| EGAS00001002624 | EGA
Project description:Obesity is a major risk factor for many common diseases and has a significant heritable component. While clinical and large-scale population studies have identified several genes harbouring rare alleles with large effects on obesity risk, there are likely many unknown genes with highly penetrant effects remaining. To this end, we performed whole exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare, loss of function variants in two genes – BSN and APBA1 – with effects on BMI substantially larger than well-established obesity genes such as MC4R. One in ~6500 individuals carry a heterozygous protein truncating variant (PTV) in BSN, which confers a 6.6, 3.7 and 3-fold higher risk of severe obesity (BMI >40kg/m2), non-alcoholic fatty liver disease and type 2 diabetes, respectively. Rare PTVs in BSN were found in three patients with severe early onset obesity, but in contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN PTVs magnified the influence of common genetic variants associated with BMI, with a common polygenic score exhibiting an effect on BMI twice as large in BSN PTV carriers than non-carriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human iPSC-derived hypothalamic neurons. These approaches highlighted a network of differentially expressed genes that were collectively enriched for genomic regions associated with BMI, and suggest emerging roles for neurodevelopment, neurogenesis, and altered neuronal oxidative phosphorylation in the etiology of obesity.
2024-01-29 | GSE243112 | GEO
Project description:Whole-exome sequencing of severe Long QT Syndrome cases
| PRJNA314701 | ENA
Project description:Human Core Exome Genotyping for 1471 samples from the STudy Into Lean and Thin Subjects (STILTS) cohort
| EGAD00010001622 | EGA
Project description:Background: Severe combined immunodeficiency (SCID) is characterized by arrested T lymphocyte production and B lymphocyte dysfunction, resulting in life-threatening infections. Early diagnosis of SCID through population-based newborn screening (NBS) optimizes clinical management and outcomes, and also permits identification of previously unknown factors essential for human lymphocyte development. Methods: SCID was detected, prior to onset of infections, by NBS of T cell receptor excision circles, a biomarker for thymic output. Upon confirmation, the affected baby was treated by allogeneic hematopoietic cell transplantation (HCT). The genetic cause was sought by exome sequencing of the patient and parents, followed by functional analysis of a prioritized candidate gene using human hematopoietic stem cells (HSC) and zebrafish embryos. Results: An infant with leaky SCID, craniofacial and dermal abnormalities, and absent corpus callosum had his immune deficit fully corrected by HCT. Exome sequencing revealed a heterozygous, de novo, missense mutation pN441K in BCL11B. The mutant Bcl11b protein had dominant negative activity, abrogating the ability of wild type Bcl11b to bind DNA, arresting T cell lineage development and disrupting HSC migration, revealing a novel function of Bcl11b. The patientâs defects, recapitulated in Bcl11b-deficient zebrafish, were reversed by ectopic expression of intact, but not mutant, human BCL11B. Conclusions: Newborn screening facilitated treatment and identification of a novel etiology for human SCID. Coupling exome sequencing with candidate gene evaluation in human HSC and in zebrafish revealed that a constitutional BCL11B mutation causes human multisystem anomalies with SCID, while also revealing a novel, pre-thymic role for Bcl11b in hematopoietic progenitors. 3 samples were analyzed in duplicate, Sample 1 was human HSC transduced with GFP only lentivirus which served as controls, Sample 2 was human HSC transduced with lentivirus expressing FLAG-tagged WT BCL11B and GFP, Sample 3 was human HSC transduced with lentivirus expressing FLAG-tagged mutant BCL11B and GFP
2016-07-29 | E-GEOD-84941 | biostudies-arrayexpress
Project description:Younger age and VTE recurrence are more likely to be caused by genetic risk factors than secondary VTE in older patients who more likely have comorbidities. When the exome rare variant genotyping database of the Scripps VTE Registry for adults < 55 yrs old was generated and analyzed for single nucleotide polymorphisms (SNPs). Two F5 related SNPs (rs6025, factor V Leiden and rs6687813) exceeded significance (FDR (false discovery rate) p < 0.05). No other variants met genome-wide significance. When the data for the subgroup of cases with recurrent VTE that are more likely to have genetic risk factors than cases with a single VTE episode were compared to controls (N=211 controls and N=32 recurrent VTE cases), 28 SNPs, including the F5 rs6025 SNP, achieved significance (FDR p < 0.05).
2021-12-04 | GSE76016 | GEO