Post-mortem cytogenomic investigations in patients with congenital malformations

Dias, Alexandre Torchio; Zanardo, Évelin Aline; Dutra, Roberta Lelis; Piazzon, Flávia Balbo; Novo-Filho, Gil Monteiro; Montenegro, Marília M.; Nascimento, A. M.; Rocha, Mariana Vilela; Madia, F. A. R.; Costa, Thaís Virgínia Moura Machado; Milani, Cíntia; Schultz, Regina; Gonçalves, Fernanda T.; Fridman, Cíntia; Yamamoto, Guilherme Lopes; Bertola, Débora Romeo; Kim, Chong; Kulikowski, Leslie Domenici

doi:10.1016/j.yexmp.2016.07.003

Cited by 5 publications

(2 citation statements)

References 30 publications

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“…Human postmortem tissue, representing a type of valuable biological material, is widely used in various fields of study including biology, pathology, and forensic medicine 1–3 . Research using postmortem tissues from autopsies has been fundamental for improving knowledge of many diseases, including neurological disorders in particular 4, 5 .…”

Section: Introductionmentioning

confidence: 99%

Systematic analysis of gene expression patterns associated with postmortem interval in human tissues

Zhu

Wang

Yin

et al. 2017

Sci Rep

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Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. A key factor in this process is the postmortem interval (PMI), which is defined as the interval between death and sample collection. However, global patterns of postmortem mRNA degradation at individual gene levels across diverse human tissues remain largely unknown. In this study, we performed a systematic analysis of alteration of gene expression associated with PMI in human tissues. From the Genotype-Tissue Expression (GTEx) database, we evaluated gene expression levels of 2,016 high-quality postmortem samples from 316 donors of European descent, with PMI ranging from 1 to 27 hours. We found that PMI-related mRNA degradation is tissue-specific, gene-specific, and even genotype-dependent, thus drawing a more comprehensive picture of PMI-associated gene expression across diverse human tissues. Additionally, we also identified 266 differentially variable (DV) genes, such as DEFB4B and IFNG, whose expression is significantly dispersed between short PMI (S-PMI) and long PMI (L-PMI) groups. In summary, our analyses provide a comprehensive profile of PMI-associated gene expression, which will help interpret gene expression patterns in the evaluation of postmortem tissues.

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Section: Introductionmentioning

confidence: 99%

Systematic analysis of gene expression patterns associated with postmortem interval in human tissues

Zhu

Wang

Yin

et al. 2017

Sci Rep

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“…Until recently, the study of human neurodevelopmental disorders has been limited by the fact that direct cellular and molecular investigation of human brain cells cannot be undertaken on living patients affected by these disorders. Post-mortem [97][98][99] and animal studies have provided substantial knowledge and important insights into human brain biology and pathology but both of these techniques have had inherent limitations. Although animal models have contributed greatly to our understanding of neurodevelopmental disorders, as they can be both genetically and pharmacologically manipulated, facilitating the examination of many aspects of neurogenesis and synaptogenesis under controlled conditions, they may not always be able to recapitulate the human phenotype, in particular when behavioral, affective and cognitive changes are the principal phenotypes of the disorder and the same limitation has also partially hindered the analysis of CNVs [100].…”

Section: Cnv Mouse Modelsmentioning

confidence: 99%

A Link between Genetic Disorders and Cellular Impairment, Using Human Induced Pluripotent Stem Cells to Reveal the Functional Consequences of Copy Number Variations in the Central Nervous System—A Close Look at Chromosome 15

Casamassa

Ferrari

Gelati

et al. 2020

IJMS

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Recent cutting-edge human genetics technology has allowed us to identify copy number variations (CNVs) and has provided new insights for understanding causative mechanisms of human diseases. A growing number of studies show that CNVs could be associated with physiological mechanisms linked to evolutionary trigger, as well as to the pathogenesis of various diseases, including cancer, autoimmune disease and mental disorders such as autism spectrum disorders, schizophrenia, intellectual disabilities or attention-deficit/hyperactivity disorder. Their incomplete penetrance and variable expressivity make diagnosis difficult and hinder comprehension of the mechanistic bases of these disorders. Additional elements such as co-presence of other CNVs, genomic background and environmental factors are involved in determining the final phenotype associated with a CNV. Genetically engineered animal models are helpful tools for understanding the behavioral consequences of CNVs. However, the genetic background and the biology of these animal model systems have sometimes led to confusing results. New cellular models obtained through somatic cellular reprogramming technology that produce induced pluripotent stem cells (iPSCs) from human subjects are being used to explore the mechanisms involved in the pathogenic consequences of CNVs. Considering the vast quantity of CNVs found in the human genome, we intend to focus on reviewing the current literature on the use of iPSCs carrying CNVs on chromosome 15, highlighting advantages and limits of this system with respect to mouse model systems.

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Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities

Chen

Ko²,

Wang

et al. 2018

Taiwanese Journal of Obstetrics and Gynecology

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Post-mortem cytogenomic investigations in patients with congenital malformations

Cited by 5 publications

References 30 publications

Systematic analysis of gene expression patterns associated with postmortem interval in human tissues

Systematic analysis of gene expression patterns associated with postmortem interval in human tissues

A Link between Genetic Disorders and Cellular Impairment, Using Human Induced Pluripotent Stem Cells to Reveal the Functional Consequences of Copy Number Variations in the Central Nervous System—A Close Look at Chromosome 15

Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities

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