Sequencing probands and families with severe insulin resistance syndromes
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ABSTRACT:
PROVIDER: EGAS00001000488 | EGA |
REPOSITORIES: EGA
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Project description:This is an ongoing project and continuation to all the sequencing we have been doing over the last few years. We have some additional families and probands with syndromes of insulin resistance not previously sequenced within uk10k or other core funded projects. We would like to complete the sequencing in all of the good quality families and probands we have, this would require another ~50 samples to be WES sequenced. This cohort has already proven to be a rich source of interesting findings with papers in Science and Nature genetics.
| EGAD00001000694 | EGA
Project description:Objectives:
1. To examine the variations in clinical features, survival outcomes, family history, and health behavior among proband patients who are known or suspected to have a hereditary colorectal cancer syndrome
2. To compare the clinical features, survival outcomes, and health behavior of the proband vs. his/her family members who may or may not be affected by the hereditary colorectal cancer syndrome
3. To explore for correlations between germline genetic variations in both the probands and family members with observed variations in the overall disease phenotype across probands and kindreds, within a given syndrome. Disease phenotype is defined to include: (1) clinicopathologic features including patient demographics and oncologic outcomes; (2) clinical manifestations of disease including the timing, spectrum and severity of CRC and extracolonic cancers. Genetic variations may include the specific codon mutated, the type of mutation and sequence alteration (e.g. nonsense, missense etc), chromosomal/gene copy number changes, and gene polymorphisms.
4. To explore for correlations between germline genetic variations in both the probands and family members with observed variations in somatic CRC tumor biology, including tumor pathology and other tumor molecular markers
| 2222117 | ecrin-mdr-crc
Project description:Introduction Aminoacyl tRNA-synthetases are ubiquitously expressed enzymes that attach amino acids to their cognate tRNA molecule. Mutations in several of the aminoacyl tRNA-syntheases are described to cause peripheral neuropathy, i.e. AARS1, GARS1, HARS1, YARS1 and WARS1. The Alanyl-tRNA Synthetase (AARS) is encoded by the AARS1. Bi-allelic mutations have been described responsible for epileptic encephalopathy with persistent myelination defect, while mutation in a single allele cause Charcot-Marie-Tooth disease type 2 (CMT2). Do date it is uncertain how a single AARS1 mutation cause tissue specific neuropathy. Methods The AARS1 was sequenced by next-generation sequencing in probands. Family members were examined by Sanger sequencing. Blood samples from affected and healthy controls were used for quantitative RNA analysis, biochemical analysis of alanine, and proteomics. Results Three Norwegian CMT2 families carried the same novel heterozygous AARS1 variant (NM_001605.2:c.976C>T p.(Arg326Trp)). The three families consisted of in total 17 genetically examined family members, of which 11 individuals carried the AARS1 variant and six unaffected individuals did not carry the variant. All individuals carrying the AARS1 variant presented with a mild to moderately severe CMT2 phenotype with adult onset, except a man age 91 years (reported by his son). Label-free quantitative proteomic analysis of four affected individuals pointed towards an effect on the immune system, comprising proteins known to represent components of systemic response to chronic injury and inflammation. Interestingly, a wide-spread impact on mitochondrial dysfunction was identified. Specifically, the oxidative phosphorylation complexes I, IV and V were highly downregulated. Conclusion Three Norwegian CMT2 families with an AARS1 variant, suggests mitochondrial dysfunction in AARS1 neuropathy.
2022-10-14 | PXD023842 | Pride
Project description:Barrett?s oesophagus is common in the UK affecting 2 % of the population. Family history has been
recorded among the 4000 Barrett's cases collected so far and have 241 families. Among them we
have assessed 6 multiplex families with proven Barrett?s and defined as having 1 pro band and at
least 3 affected first degree members. We propose to exome sequence the probands of these six
families to assess the presence of pathogenic rare coding variants.
| EGAD00001002181 | EGA
Project description:Barrett?s oesophagus is common in the UK affecting 2 % of the population. Family history has been
recorded among the 4000 Barrett's cases collected so far and have 241 families. Among them we
have assessed 6 multiplex families with proven Barrett?s and defined as having 1 pro band and at
least 3 affected first degree members. We propose to exome sequence the probands of these six
families to assess the presence of pathogenic rare coding variants.
| EGAS00001000531 | EGA
Project description:Mental retardation (MR) is a non-progressive cognitive impairment affecting 2 to 3% of the Western population. So far, point mutations and subtle deletions and insertions have been shown to represent only a proportion (<40%) of genetic causes underlying X-linked mental retardation (XLMR). We have screened a subset of 300 presumable X-linked families by X chromosome-specific array-CGH and identified 6 families with overlapping microduplications at Xp11.22 containing two candidate genes; both of which showed overexpression in the affected individuals. Array-CGH data revealed aberrant Cy5/Cy3 log2 ratios for different but overlapping sets of clones indicating varying sizes of these duplications in the different families. X chromosome-specific array-CGH performed for probands of families A, FAM3, B, MRX17, C, MRX31, and D, A057, revealing the duplications at Xp11.22. DNA from two unrelated MR patients were differentially labeled and co-hybridized onto the X-array. The patients with duplications were hybridized in Cy5 against unrelated MR patients, named Pat XY1-6, in the Cy3 channel.
2010-06-25 | E-GEOD-9143 | biostudies-arrayexpress
Project description:Purpose: To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) in families mapped to the PPCD1 locus and in affected individuals without ZEB1 coding region mutations. Methods: The promoter and/or coding regions of OVOL2 were screened in the PPCD family in which linkage analysis established the PPCD1 locus and in 26 PPCD probands who did not harbor a ZEB1 mutation. Copy number variation (CNV) analysis in the PPCD1 and PPCD3 intervals was performed on DNA samples from eight probands using aCGH. Luciferase reporter assays were performed in human corneal endothelial cells to determine the impact of the identified potentially pathogenic variants on OVOL2 promoter activity. Results: OVOL2 screening in the first PPCD1-linked family demonstrated segregation of the c.-307T>C variant with the affected phenotype. In the other 26 probands screened, one heterozygous coding region variant and five promoter region heterozygous variants were identified, though none are likely pathogenic based on allele frequency. Array CGH in the PPCD1 and PPCD3 loci excluded the presence of CNV involving either OVOL2 or ZEB1, respectively. The c.-307T>C variant demonstrated increased promoter activity when compared to the wild-type sequence. Conclusions: The previously identified and presumed pathogenic OVOL2 promoter variant c.-307T>C was identified in the PPCD family that established the PPCD1 locus. However, the failure to identify presumed pathogenic coding or non-coding OVOL2 or ZEB1 variants, or CNV involving the PPCD1 and PPCD3 loci in 26 other PPCD probands suggests that other genetic loci may be involved in the pathogenesis of PPCD.
2017-03-08 | GSE84940 | GEO
Project description:Topping is an important cultivating measure for flue-cured tobacco, and many genes had been found to be differentially expressed in response to topping. But it is still unclear how these genes are regulated. MiRNAs play a critical role in post-transcriptional gene regulation, so we sequenced two sRNA libraries from tobacco roots before and after topping, with a view to exploring transcriptional differences in miRNAs.Two sRNA libraries were generated from tobacco roots before and after topping. Solexa high-throughput sequencing of tobacco small RNAs revealed a total of 12,104,207 and 11,292,018 reads representing 3,633,398 and 3,084,102 distinct sequences before and after topping. The expressions of 136 conserved miRNAs (belonging to 32 families) and 126 new miRNAs (belonging to 77 families) were determined. There were three major conserved miRNAs families (nta-miR156, nta-miR172 and nta-miR171) and two major new miRNAs families (nta-miRn2 and nta-miRn26). All of these identified miRNAs can be folded into characteristic miRNA stem-loop secondary hairpin structures, and qRT-PCR was adopted to validate and measure the expression of miRNAs. Putative targets were identified for 133 out of 136 conserved miRNAs and 126 new miRNAs. Of these miRNAs whose targets had been identified, the miRNAs which change markedly (>2 folds) belong to 53 families and their targets have different biological functions including development, response to stress, response to hormone, N metabolism, C metabolism, signal transduction, nucleic acid metabolism and other metabolism. Some interesting targets for miRNAs had been determined.
2014-11-01 | GSE33370 | GEO
Project description:Topping is an important cultivating measure for flue-cured tobacco, and many genes had been found to be differentially expressed in response to topping. But it is still unclear how these genes are regulated. MiRNAs play a critical role in post-transcriptional gene regulation, so we sequenced two sRNA libraries from tobacco roots before and after topping, with a view to exploring transcriptional differences in miRNAs.Two sRNA libraries were generated from tobacco roots before and after topping. Solexa high-throughput sequencing of tobacco small RNAs revealed a total of 12,104,207 and 11,292,018 reads representing 3,633,398 and 3,084,102 distinct sequences before and after topping. The expressions of 136 conserved miRNAs (belonging to 32 families) and 126 new miRNAs (belonging to 77 families) were determined. There were three major conserved miRNAs families (nta-miR156, nta-miR172 and nta-miR171) and two major new miRNAs families (nta-miRn2 and nta-miRn26). All of these identified miRNAs can be folded into characteristic miRNA stem-loop secondary hairpin structures, and qRT-PCR was adopted to validate and measure the expression of miRNAs. Putative targets were identified for 133 out of 136 conserved miRNAs and 126 new miRNAs. Of these miRNAs whose targets had been identified, the miRNAs which change markedly (>2 folds) belong to 53 families and their targets have different biological functions including development, response to stress, response to hormone, N metabolism, C metabolism, signal transduction, nucleic acid metabolism and other metabolism. Some interesting targets for miRNAs had been determined. 2 samples examined:roots before and after topping
2014-11-01 | E-GEOD-33370 | biostudies-arrayexpress