Mitochondrial DNA sequences of familial (maternal vs. non-maternal) ALS cases in whole blood, platelets and white blood cells
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ABSTRACT:
PROVIDER: PRJNA869683 | ENA |
REPOSITORIES: ENA
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Project description:To address the question of whether mtDNA mutations might play a role in familiar ALS (fALS), mtDNA was isolated from whole blood (WB), white blood cells (WBC) and platelets (PLT) from fALS patients and the mitochondrial genome was analyzed using a mtDNA resequencing array (Affymetrix MitoChip v2.0) that allows detection of low-level heteroplasmy in addition to the conventional homoplasmic or heteroplasmic mutations. We distinguished between fALS cases with a prominent maternal (mat) inheritance pattern and fALS cases that do not point to a maternal inheritance pattern (non-mat). As additional controls we compared our results to healthy age and sex matched individuals without any known neurodegenerative background. With this we are aiming to get a deeper insight into a possible role of mtDNA alterations acting as a disease modifier in a subgroup of ALS patients presenting with a maternal transmission of the disease.
2023-07-28 | GSE211250 | GEO
Project description:The objective is to quantify the contribution of genetic and common environmental effects in the familial resemblances of whole blood genome-wide gene expression levels. We also make comparisons with familial resemblances in blood leukocytes genome-wide DNA methylation levels in the same cohort in order to further investigate biological mechanims.
2018-05-18 | GSE114620 | GEO
Project description:Familial Blood and Lymph Node Cancers
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Project description:Familial resemblances in human whole blood transcriptome
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Project description:Familial Blood and Lymph Node Cancers - Waldenstrom macroglobulinemia
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Project description:Rationale: Idiopathic interstitial pneumonia (IIP) and its’ familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in understanding the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown. Objectives: To evaluate gene expression in the lung tissue from patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) that were either familial or non-familial in origin and compare them to gene expression from normal lung parenchyma. Methods: We profiled RNA from lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal controls on a whole human genome oligonucleotide microarray. Results: Significant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. Keywords: disease state analysis
2006-10-01 | GSE5774 | GEO
Project description:Early diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement. A large proportion of platelets exhibited changes in the overall shape and depletion of organelles in AML. Notably, 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae, accompanied by a significant drop in ATP levels and altered expression of metabolism-related gene signatures. Our study demonstrates that detectable structural changes in pre-leukemic platelets may serve as a biomarker for the early diagnosis of AML.
2022-02-08 | GSE189844 | GEO
Project description:The shortage of platelets is becoming increasingly prominent owing to their short shelf life, limited supply, and increasing demand in response to public health incidents. It is an attractive idea to obtain large numbers of transfusible megakaryocytes (MKs) and platelets from somatic cells via cell lineage reprogramming. However, generating human MKs from somatic cells using a pharmacological reprogramming approach has not been widely explored. Here, we report the successful generation of human induced MKs (iMKs) from cord blood erythroblasts (EBs) using a chemical reprogramming strategy with a combination of four small molecules (4M): Bix01294, RG108, VPA, and PD0325901. The iMKs exhibited the ability to produce proplatelets and release vital functional platelets in vitro, demonstrating their similarity to natural MKs. Importantly, after injection into mice, iMKs were able to mature and give rise to functional platelets that were incorporated into newly formed thrombi. The reprogramming process was carefully examined using single-cell RNA sequencing, which revealed an efficient, rapid, and successful cell fate conversion of EBs to iMKs by 4M via the intermediate state of bipotent precursors. Assay for transposase-accessible chromatin sequencing results indicated that 4M induced genome-wide chromatin remodeling during MK reprogramming from EBs. 4M drove the transition of the transcription factor gene network by downregulating the key erythroid transcription factor genes KLF1 and MYB and subsequently upregulating MK development-associated transcription factor genes, including FLI1 and MEIS1. This process eventually led human cord blood EBs to acquire the MK fate. Thus, our chemical reprogramming of cord blood EBs to iMKs provides a simple and efficient approach to generating clinically transfusible MKs and platelets.
2022-08-28 | GSE207654 | GEO
Project description:Familial cases of MPN are usually transmitted by autosomal inheritance with incomplete penetrance, appear in adulthood, and demonstrate acquired genetic abnormalities that are similar to those identified in sporadic cases such as JAK2V617F and TET2 mutations. Linkage and segregation analyses indicate that genetic predisposition to MPN cannot be related to a common alteration and rather involves a number of susceptibility loci responsible for independent familial aggregations. Identification of these susceptibility loci may improve our understanding of the mechanisms of predisposition, which may result either in the induction of a genetic instability, favoring the acquisition of oncogenic mutations or corresponds to a fertile ground for selection of somatic mutations. Here, we describe a newly identified germline copy number variation (CNV) that predisposes to essential thrombocythemia (ET) which rapidly progress to myelofibrosis (MF) and MDS/AML. Using induced pluripotent stem and primary cells to explore hematopoietic differentiation, we demonstrate that overexpressed ATG2B and GSKIP enhance hematopoietic progenitor differentiation, including megakaryocytic through increasing their sensitivity to TPO. To evaluate the overexpression of ATG2B and GSKIP in patients and their role in hematopoiesis, we generated EBV cell lines from peripheral blood of patients or relatives. These cell lines were cultured in RPMI with 20% FBS. The present study concerns gene expression of EBV cell lines from patients and controls after RNA extraction (qiagen kit). Gene expression was performed in single color on Agilent8x60K v2 Human whole genome (design 039494) in replicates 15 cell lines from affected patients and 9 non affected controls).
2015-08-17 | E-MTAB-3570 | biostudies-arrayexpress
Project description:Both the fetus and the mother who are involved in maternal anti-fetal rejection during pregnancy show distinct alterations in the peripheral blood transcriptome Total RNA isolated from umbilical cord blood and maternal blood was compared between cases without (Normal) and with maternal anti-fetal rejection (FIRS2) using whole genome DASL assay.
2012-03-31 | E-GEOD-28387 | biostudies-arrayexpress