4078 results for "*geneti*"

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• Recurrent somatic JAK-STAT mutations within a novel RUNX1-mutated pedigree

  The acquisition of somatic mutations is an emerging field of investigation in familial leukemia. Currently, genetic profiles in familial MDS/AML are considered analogous to sporadic disease, although the patterns of clonal evolution within families are poorly defined. We performed whole exome profiling of tumour samples from a novel RUNX1 mutated family, to determine the stepwise evolution of MDS/AML across 4 young siblings. Three siblings developed monocytic AML/RAEB2 at 5 years of age, with hepatosplenomegaly and somatic mutations upregulating JAK-STAT signalling, the latter are typically detected in <5% of sporadic MDS/AML. Two siblings acquired the canonical JAK2 V617F mutation, while another acquired a unique missense mutation of SH2B3, a negative regulator of JAK2. Notably, 2/3 siblings demonstrated dosage amplification of these mutations due to acquired uniparental disomy of chromosomes 9p and 12q (encompassing JAK2 and SH2B3, respectively). All 4 siblings were heterozygous for the 46/1 JAK2 haplotype associated with predisposition to sporadic V617F myeloproliferative disorders, which likely influenced the acquisition of JAK2 mutations. Our findings provide further evidence that relatives with shared germline mutations may acquire somatic mutations in a non-random manner leading to convergent patterns of disease evolution.

  Study EGAS00001001862

• Adenoma to Carcinoma transition in Colorectal Cancer

  Although colorectal carcinoma development is well accepted as a step-wise and sequential process, it is commonly investigated using non-sequential adenoma and carcinoma samples. Here we compared molecular pathologies of the earliest carcinoma stages with those in their adenomatous precursors to unravel common and divergent genetic traits between matched neoplasms with a shared evolutionary history but different contemporary biology.

  Study EGAS00001003468

• Illumina Human OmniExpress genotyping data from the Cretan Greek isolate collection HELIC MANOLIS

  Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina Human OmniExpress BeadChip array. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages. Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org **The data may not be used for population genetics analyses**

  Study EGAS00001000687

• A genome scan for genes underlying adult body size differences between Central African hunter-gatherers and farmers.

  The evolutionary and biological bases of the Central African pygmy phenotype, a characteristic of rainforest huntergatherers defined by reduced body size compared with neighboring farmers, remain largely unknown. Here, we perform a joint investigation in Central African hunter-gatherers and farmers of adult standing height, sitting height, leg length, and body mass index (BMI), considering 358 hunter-gatherers and 169 farmers with genotypes for 153,798 SNPs. In addition to reduced standing heights, hunter-gatherers have shorter sitting heights and leg lengths and higher sitting/standing height ratios than farmers and lower BMI for males. Standing height, sitting height, and leg length are strongly correlated with inferred levels of farmer genetic ancestry, whereas BMI is only weakly correlated, perhaps reflecting greater contributions of non-genetic factors to body weight than to height. Single- and multi-marker association tests identify one region and eight genes associated with hunter-gatherer/farmer status, and 24 genes associated with the height-related traits. Many of these genes have putative functions consistent with roles in determining their associated traits and the pygmy phenotype, and they include three associated with standing height in non-Africans (PRKG1, DSCAM, MAGI2). We find evidence that European height-associated SNPs or variants in linkage disequilibrium with them contribute to standing- and sitting-height determination in Central Africans, but not to the differential status of hunter-gatherers and farmers. These findings provide new insights into the biological basis of the pygmy phenotype, and they highlight the potential of cross-population studies for exploring the genetic basis of phenotypes that vary naturally across populations. Pemberton et al. Human Genetics 2018 https://doi.org/10.1007/s00439-018-1902-3

  Study EGAS00001002975

• Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population

  We recently showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at investigating the genetic determinants for glycated hemoglobin (HbA1C). We found no novel associations but saw that for 10 out of 15 known HbA1C loci that the effects in Greenlandic Inuit were similar to previously reported. One locus, ANK1, showed a significant ancestral population specific effect. Our results shed light on the genetics effects across ethnicites.

  Study EGAS00001002641

• Autozygosity_pilot___QMUL

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.

  Study EGAS00001000717

• ESGI_Exome_sequencing_in_Circulating_Tumor_Cells_to_determine_therapy_related_markers_____

  The objectives of this project are the identification of markers related to cancer therapy resistance in the blood of breast cancer patients and to study the genetic changes in cancer cells during this development of resistance. Whole genome amplified DNA from Circulating Tumor Cells (CTCs), selected during the course of systemic treatment from blood of metastatic breast cancer patients, will be exome sequenced . The patients selected for this study did not respond to therapy.

  Study EGAS00001000747

• HipSci HumanExome BeadChip analysis - Bleeding and Platelet disorders

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.

  Study EGAS00001002013

• Molecular_diagnosis_of_albinism

  Albinism is genetically heterogeneous rare genetic condition affecting 1:17000 in the Western world (but more frequent in Africa) whose main feature is a profound visual impairment, characterised by foveal hypoplasia, abnormal chiasmatic connections, nystagmus and photofobia. All these features result in severly altered visual acuity (<0,1), absent depth perception and poor night vision. People with albinism are primarily visually handicapped. In addition, for some types of albinism, the visual phenotype can be presented with partial or total hypopigmentation, hence resulting in a secondary phenotype which can lead to skin cancer if skin is not adequately protected. Recently a new syndrome has been described, FHONDA, with the same visual abnormalities of albinism but without pigment alteration. The traditional classification differentiates Oculoculatenous albinism (OCA), where hypopigmentation involves hair, skin and eyes versus Ocular Albinism (OA), where hypopigmentation only affects the eyes. These are non-sydrimic types of albinism. Some syndromic forms (Hermansky-Pudlak=HPS, Chediak-Higashi=CHS) affect cells beyond pigment cells, present in the lungs, immune system, platelets and intestines, resulting in more severe phenotypes that can be fatal. Mutations in at least 19 genes are assocaited with the corresponding types of albinism. Most hospitals will only diagnose the most frequent cases using traditional Sanger, MLPA approaches. Some will use CGH arrays. We aim to diagnose all cases of albinism through the Albinochip proposal, which combines a Sequenom first step of known mutations combined with subsequent NGS approaches. In some cases we fail to find a second mutation, these are good candidates for further full exome analyses. 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/

  Study EGAS00001002068

• Integrated genetic and epigenetic analysis defines novel molecular clusters in rhabdomyosarcoma

  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. To unravel the genetic/epigenetic basis of RMS, we studied 60 RMS cases using whole exome/transcriptome sequencing, copy number (CN) profiling, and DNA methylome analysis. Based on DNA methylation patterns, RMS was clustered into 4 distinct subtypes, which exhibited remarkable correlation with mutation/CN profiles, histological phenotypes, and clinical behaviors. A1 and A2 subtypes, especially A1, largely corresponded to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes were characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite generally poor prognosis in RMS, patients in E1 cluster exceptionally showed excellent prognosis. Our results highlight the close relationship between DNA methylation status and gene mutations and biological behavior in RMS.

  Study EGAS00001000884