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Table of Content

Open Access Review

Oncogenes Orchestrate Immunosuppressive Stroma in Gastric Adenocarcinoma

Received: 30 June 2020;  Published: 16 September 2020;  doi: 10.21926/obm.genet.2003116

Abstract

Gastric adenocarcinoma (GAC) is among the three most common cancers in the world. The majority of GAC patients are diagnosed in an advanced stage and have a median survival of ~9 months. There are limited effective therapeutic strategies available in the clinic and currently U.S. Food and Drug Administration (FDA) approved immune therapy is programmed death-1 (PD-1) antibodies (e.g. pembrolizumab) but only a few patients seem to benefit. Transformation to cancer occurs when multiple genes and cellular pathways are [...]

2071 9621

Open Access Opinion

Breeding “CRISPR” Crops1

Received: 21 April 2020;  Published: 13 August 2020;  doi: 10.21926/obm.genet.2003115

Abstract

The challenges which face the world today can be summed up in a few words: An increasingly congested world with dwindling areas of viable cultivated land and accelerating climate instability. The combined effect of these realities, together with the trend of striving to extend the average human life, puts the world on the path toward future catastrophe. This situation makes it imperative to seek realistic and practical solutions, which must be able to address food shortages and climate problems in a timely manner. [...]

2058 9664

Open Access Review

Detection of Circulating Tumor DNA in Solid Tumors

Received: 27 May 2020;  Published: 06 August 2020;  doi: 10.21926/obm.genet.2003114

Abstract

Cancer is characterized by sequential and progressive genetic and epigenetic alterations in key proto-oncogenes and tumor suppressor genes, which ultimately lead to tumor development. Advances in the technology of analysis of molecular mechanisms have increased the efficiency of clinical management of cancer patients. Recent years have witnessed a progressive development in technologies that enable the detection of specific molecular abnormalities associated with various types of solid tumors in body fluids, a proc [...]

2062 11109

Open Access Review

“Evolution” of Embryogenesis: Complexity of the Early Developmental Stages in the Animal Kingdom

Received: 16 March 2020;  Published: 02 July 2020;  doi: 10.21926/obm.genet.2003113

Abstract

Multicellularity has gained the advantage over the unicellular world by expanding the number of increasingly more complex tissues that achieve advanced and specific functions. This same event gave rise to the most evolved group of organisms, namely mammals. Even though the complexity of multicellular organisms does not necessarily provide them with excellent adaptation modes performed by unicellular and prokaryotic organisms, this complexity per se stands as one of the greatest phenomena in biology. However, there [...]

2852 18862

Open Access Original Research

Genetic Variants of Targetable Cancer-related Genes in Vestibular Schwannomas

Received: 02 May 2020;  Published: 28 June 2020;  doi: 10.21926/obm.genet.2002112

Abstract

Background: Vestibular schwannoma is an intracranial tumor which can lead to devastating neurological deficit and is prone to recurrence after surgery. Patients with inherited neurofibromatosis type 2 (NF2) syndrome are particularly susceptible to bilateral and aggressive schwannomas. However, the genome of vestibular schwannomas is not well known. There is an imminent need of developing effective chemotherapeutic agents either as a primary treatment modality or as adjuvant therapy for these patients. Methods: Here [...]

2098 10782

Open Access Review

Genetic Explanations for Fertility Disorders

Received: 02 May 2020;  Published: 23 June 2020;  doi: 10.21926/obm.genet.2002111

Abstract

This article reviews the genetic testing of infertility disorders. Genetic abnormalities can lead to disturbances of sexual development and hamper reproduction by influencing gamete production and maturation, fertilization, and embryonic development. Until now, the vast majority of detectable genetic abnormalities causing infertility were chromosomal abnormalities in both males and females. However, the number of monogenetic disorders, which play a role in disturbing fertility, such as single gene defects or comple [...]

2107 11825

Open Access Review

Splicing HAC1/XBP1 mRNAs in Cytoplasm: The Non-Conventional mRNA Splicing Reaction in the Unfolded Protein Response

Received: 23 March 2020;  Published: 22 May 2020;  doi: 10.21926/obm.genet.2002110

Abstract

The majority of the secretory and transmembrane proteins are folded in the endoplasmic reticulum (ER). When unfolded proteins accumulate in the ER, a collective of signalling pathways, termed the unfolded protein response (UPR), are activated to restore the ER protein folding homeostasis. The most evolutionarily conserved branch of UPR is mediated by the kinase/endoribonuclease Ire1. Ire1 mediates a cytosolic non-conventional mRNA splicing reaction of HAC1 mRNA in yeast and XBP1 mRNA in mammalian cells. The spliced [...]

2615 13350

Open Access Technical Note

HER2 FISH for Breast Cancer: Advances in Quantitative Image Analysis and Automation

Received: 02 March 2020;  Published: 13 May 2020;  doi: 10.21926/obm.genet.2002109

Abstract

Quantitative image analysis of the status of human epidermal growth factor receptor 2 (HER2) by both immunohistochemistry staining and fluorescent in situ hybridization (FISH) is important for the treatment of breast cancer. Guidelines of the American Society for Clinical Oncology and College of American Pathologists, for HER2 FISH, have evolved over time to improve test accuracy, and efforts have been made to better address the problems with the interpretation that are encountered with borderline-positive cases. S [...]

2467 22216

Open Access Research Article

Professionals’ Views on Offering Pre-Natal Testing for Adult Onset Cancer Susceptibility. Reconciling Personal and Professional Ethical Conflicts, Coping Strategies and Need for Policy Transparency

Received: 30 December 2019;  Published: 26 April 2020;  doi: 10.21926/obm.genet.2002108

Abstract

This paper explores views of healthcare professionals (HCPs) in genetics and foetal medicine settings on offering pre-natal diagnosis (PND) for adult onset cancer susceptibility (AOCS) genes. Study participants came from different disciplinary backgrounds and all had considered implications of offering PND for AOCS, directly or indirectly, from professional and personal perspectives. Foetal medicine and genetics teams are accustomed to offering PND with the possibility of terminating an affected foetus on the basis [...]

2045 10658

Open Access Original Research

MSIGNET: A Bayesian Approach for Disease-associated Gene Network Identification

Received: 19 October 2019;  Published: 07 April 2020;  doi: 10.21926/obm.genet.2002107

Abstract

The analysis of gene networks and signalling pathways plays a key role in understanding gene functions, i.e., their effects on the development of a particular disease. Yet, for many heterogeneous diseases, the number of known disease-associated genes is limited. Identifying disease-associated genes is still an open challenge. To understand the functions of genes associated with a disease, we develop a Metropolis-Hastings sampling based SIGnificant NETwork (MSIGNET) identification approach. MSIGNET integrates diseas [...]

2030 11119

Open Access Case Report

Knight in Splicing Armor: Alternative Splicing as a Neuroprotective Mechanism

Received: 13 January 2020;  Published: 20 March 2020;  doi: 10.21926/obm.genet.2001106

Abstract

By adjusting gene expression in response to environmental changes, cells can optimize fitness as needed. Alternative splicing is one of the most important post-transcriptional regulation steps, broadly involved in diverse physiological and pathological conditions. Here, we present 5 cases of alternative splicing conferring increased neuroprotection through diverse mechanisms. These examples highlight the enormous power of alternative splicing in maintaining viability of neurons. From pre-mRNA secondary structure al [...]

1925 12157

Open Access Editorial

Epigenetics of Obesity and Diabetes: Emerging Roles and Mechanisms of Non-coding RNAs

Received: 16 March 2020;  Published: 17 March 2020;  doi: 10.21926/obm.genet.2001105

1836 9507

Open Access Editorial

Plant Genetics and Gene Study

Received: 03 March 2020;  Published: 04 March 2020;  doi: 10.21926/obm.genet.2001104

1893 10445

Open Access Communication

Effective Delivery of Cancer Vaccines with Oxidatively Photo-Inactivated Transgenic Leishmania for Tumor Immunotherapy in Mouse Models

Received: 29 December 2019;  Published: 24 February 2020;  doi: 10.21926/obm.genet.2001103

Abstract

The parasitic protozoa in the genus of Leishmania have exceptionally favorable attributes for exploitation as a vehicle for safe and effective delivery of transgenically incorporated vaccines against infectious and malignant diseases. A dual suicidal mechanism was installed in Leishmania via genetic and chemical engineering in vitro for accumulation of photosensitizers, rendering them sensitive to dim light for inactivation. Leishmania so inactivated are non-viable, but immunologically competent to deliver vaccines [...]

1984 10439

Open Access Editorial

Another Productive Year

Received: 13 January 2020;  Published: 14 January 2020;  doi: 10.21926/obm.genet.2001102

Abstract

At the beginning of a new year it is always good to look both backwards and forwards and to highlight a few items that are relevant with respect to the long-term development of our journal. As everybody knows, the principle of open access publishing is that the authors pay fees (the article‐processing charges or APCs) to publish in the journal rather than that the readers pay subscription costs for the journal. Three years ago, OBM Genetics started as an open access journal publishing its first papers totally free [...]

1184 9071

Open Access Review

The Role of Genetic Counseling in Gynecological Oncology

Received: 15 July 2019;  Published: 12 December 2019;  doi: 10.21926/obm.genet.1904101

Abstract

Background: Clinical or medical genetics deals with the study and diagnosis of genetic diseases. It is oriented to the formulation of the clinical diagnosis of genetic diseases and genetic counseling to evaluate the possible reproductive risk for the patient and his/her family. The geneticists here play a role in the diagnosis and prevention of some of the diseases occurring most frequently, such as cancer and cardiovascular diseases. Methods: State-of-the-art through literature review. Results: Genetic counseling [...]

2031 16524

Open Access Hypothesis

Combination of the Hansemann-Boveri, Warburg, and Knudson Theories of Cancer, Based on Failure of Missegregation Damage Mitigation

Received: 17 July 2019;  Published: 03 December 2019;  doi: 10.21926/obm.genet.1904100

Abstract

Hansemann-Boveri’s aneuploidy theory, the Warburg effect, and the Knudson hypothesis can be viewed as different aspects of a single theory of cancer. In this, the extremely common chromosome missegregation may be the underlying cause. Chromosome missegregation is mitigated via several mechanisms. Cancer can occur only when all of these mechanisms have been inactivated in a single cell line, typically by mutation. There are at least five different repair mechanisms, implying a hit-factor of at least five. These miti [...]

2140 12210

Open Access Review

Nutrition, Cancer Genetics and Epigenetics

Received: 01 October 2019;  Published: 28 November 2019;  doi: 10.21926/obm.genet.1904099

Abstract

Epidemiological data and meta-analysis have confirmed that there exists a strong association between nutrition and disease risk. In the context of cancer, it has been demonstrated that unhealthy diets increase the risk of disease. On the other hand, major dietary interventions and lifestyle changes have been demonstrated to provide therapeutic efficacy in cancer patients. Genetic mechanisms have been reported to be associated with cancer development induced by environmental and nutritional factors. Genetics plays a [...]

2372 13933

Open Access Original Research

Diversity in the Bacterial Genus Dickeya Grouping Plant Pathogens and Waterways Isolates

Received: 25 July 2019;  Published: 26 November 2019;  doi: 10.21926/obm.genet.1904098

Abstract

Background: Genus Dickeya comprises aggressive soft rot plant pathogens with wide geographic distribution and host ranges. Ten Dickeya species were characterized. Seven of them (Dickeya chrysanthemi, D. dadantii, D. dianthicola, D. fangzhongdai, D. solani, D. paradisiaca, and D. zeae) group causative agents of maceration-associated diseases that impact a wide variety of crops or ornamentals as well as isolates from fresh water. The other three species (D. aquatica, D. lacustris, D. undicola) were recently isolated [...]

2551 16987

Open Access Review

Optimizing Phage Translation Initiation

Received: 09 June 2019;  Published: 17 October 2019;  doi: 10.21926/obm.genet.1904097

Abstract

Phage as an anti-bacterial agent must be efficient in killing bacteria, and consequently needs to replicate efficiently. Protein production is a limiting step in replication in almost all forms of life, including phages. Efficient protein production depends on the efficiency of translation initiation, elongation and termination, with translation initiation often being rate limiting. Initiation signals such as Shine-Dalgarno (SD) sequences and start codon are decoded by anti-SD sequences and initiation tRNA, respect [...]

1917 15251

Open Access Review

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Received: 14 May 2019;  Published: 14 October 2019;  doi: 10.21926/obm.genet.1904096

Abstract

Insulin-like growth factor 2 (IGF2) is a strong mitogenic peptide with an imprinted gene that is primarily involved in fetal development. It is highly expressed in the fetus where it is involved in fetal growth and tissue differentiation. However, postnatally, the expression of IGF2 decreases despite higher expression levels in the blood as compared with that of IGF1. In adults, the physiological function of IGF2 is poorly understood; however, the possibility of a metabolic function exists. Although the expression [...]

2442 16485

Open Access Short Report

Thalassemia Intermedia Caused by a Combination of a Globin Gene Triplication with Heterozygosity for β0 Thalassemia: A Case Report

Received: 19 May 2019;  Published: 17 September 2019;  doi: 10.21926/obm.genet.1903095

Abstract

Thalassemia syndromes are a group of hemoglobinopathies characterized by gene defects that disrupt normal hemoglobin production. Thalassemia intermedia (TI) is referred to as a group of disorders with a less severe form of the disease compared to thalassemia major. We present a case of a 60-year-old woman who was referred to a hematologist for chronic anemia and splenomegaly.

1855 10911

Open Access Editorial

Introduction to Genetic Screening

Received: 06 September 2019;  Published: 11 September 2019;  doi: 10.21926/obm.genet.1903094

Abstract

We present here the content and articles of this special issue on genetic screening, putting them in perspective with the field and between themselves.

1914 9058

Open Access Review

Newborn Screening for Genetic Diseases: An Overview of Current and Future Applications

Received: 01 July 2019;  Published: 06 September 2019;  doi: 10.21926/obm.genet.1903093

Abstract

Newborn screening (NBS) for inborn errors of metabolism (IEM) was introduced more than 50 years ago with the testing of phenylketonuria (PKU) using blood spots deposited on a filter paper after heel prick. NBS aims to identify early after birth inherited disorders for which clinical management and pre-symptomatic treatment will significantly decrease morbidity and mortality. While NBS for a few other disorders was implemented in some specific jurisdictions over the following decades, it is with the introduction of [...]

2356 13632

Open Access Communication

Upregulation of COX-2 in MCF7 Breast Cancer Cells When Exposed to Shear Stress

Received: 17 June 2019;  Published: 06 September 2019;  doi: 10.21926/obm.genet.1903092

Abstract

Background: Invasive breast cancer affects 1 in 8 women in the United States and causes one of the highest cancer mortality rates for women. Cyclooxygenase-2 (COX-2), a central enzyme in prostaglandin biosynthesis, is implicated in breast cancer initiation, progression, invasion, and metastasis, and has been linked to the mechanotransduction of breast cancers. However, it is not currently known if shear stress mediated mechanotransduction is affected by COX-2. Therefore, in this report, we hypothesized that COX-2 m [...]

2144 19266

Open Access Original Research

Deletion of Subtelomeric Regions in the Linear Chromosome of Variants Isolated from Streptomyces avermitilis NBRC 14893T

Received: 19 April 2019;  Published: 23 August 2019;  doi: 10.21926/obm.genet.1903091

Abstract

Background: Streptomyces avermitilis is an actinomycete that produces avermectins. The complete genome sequence of S. avermitilis K139 was determined in 2003. In our previous study, we revealed that S. avermitilis NBRC 14893T harbors two extra secondary metabolite-biosynthetic gene clusters (smBGCs), com and ptx, which are not present in strain K139. Methods: Whole-genome sequencing for S. avermitilis NBRC 14893T and ATCC 31267T was carried out by the SMRT DNA sequencing technology to determine the genomic loci enc [...]

3495 10181

Open Access Research Article

BSA-Embedded Carbonate Apatite Enhances Chemotherapeutic Effect of Paclitaxel in vitro and in vivo

Received: 29 March 2019;  Published: 15 August 2019;  doi: 10.21926/obm.genet.1903090

Abstract

Introduction of biocompatible ingredients into nano-material formulations has been studied as a strategy for the enhancement of the pharmacokinetics as well as pharmacodynamics of the final product. With the aim of enhancing drug loading and the ultimate efficacy, incorporation of Bovine Serum Albumin (BSA) into carbonate apatite (CA) nanoparticles structure was employed in the present study. As a result of BSA embedding in the CA formulation, approximately three-times higher loading efficiency was achieved for pac [...]

1827 9333

Open Access Review

Diagnosis and Treatment of Mitochondrial Abnormalities in Reproductive Medicine

Received: 08 April 2019;  Published: 14 August 2019;  doi: 10.21926/obm.genet.1903089

Abstract

Mitochondrial diseases are among the most prevalent inborn errors of metabolism. The overwhelming majority of mitochondrial diseases (about 85%) result from mutations in nuclear genes involved in oxidative phosphorylation, while some (15%) are caused by mutations in mitochondrial DNA (MtDNA). The familial mtDNA mutations are exclusively inherited from the mother. There are four main methods available to prevent the transmission of mtDNA mutations: preimplantation genetic diagnosis (PGD) or prenatal diagnosis (PND) [...]

1803 10925

Open Access Review

Next-Generation Sequencing-Based Testing in Diagnostic Oncohematology: Untangling the Knots

Received: 01 April 2019;  Published: 09 August 2019;  doi: 10.21926/obm.genet.1903088

Abstract

With the advent of next-generation sequencing (NGS), genomic profiling of tumors has been gradually introduced into the clinical setting and has become a standard in cancer care. NGS allows convenient, rapid, and inexpensive sequencing and the commercially available NGS panels enable the detection of single or global genomic alterations of germline and somatic origin. Today, genomic mutation profiling using NGS is indispensable for disease evaluation and prediction of prognosis or responsiveness to cancer therapy. [...]

1960 13109

Open Access Research Article

Family History, Genetic, and Other Cause-Related Beliefs among Breast Cancer Survivors

Received: 27 February 2019;  Published: 26 July 2019;  doi: 10.21926/obm.genet.1903087

Abstract

Patients’ lay theories about the cause of their cancer may influence patient behavior and adjustment, they have also been found to differ substantially from scientific evidence of cancer risk factors. This report describes beliefs about genetic causes of breast cancer, among 522 recently diagnosed breast cancer survivors participating in an observational study. Patients were asked to respond to an open-ended question about the cause of their cancer. Causes mentioned included family history, genetics, lifestyl [...]

1810 9853

Open Access Original Research

The Evolution of DNA Typing in Agri-Food Chain

Received: 11 June 2019;  Published: 23 July 2019;  doi: 10.21926/obm.genet.1903086

Abstract

Background: DNA typing has revolutionized not only diagnostics and forensics but also how we can analyze food. A number of techniques have been successfully applied for DNA analysis of plant-derived food. However, unlike forensics, a universally employed method has not yet emerged. Methods: A keyword-based search was performed using the ISI-Web of Science database to look for research articles on DNA testing in agri-food chain. After screening and eligibility check, a Systematic Review was compiled focusing on the [...]

1775 10315

Open Access Case Report

Constitutional Partial Proximal Trisomy 14q11.2 to 14q21: Two New Moroccan Cases and Review of the Literature

Received: 25 July 2018;  Published: 22 July 2019;  doi: 10.21926/obm.genet.1903085

Abstract

Background: A report of two new Moroccan cases with polymalformative syndrome, in which we identified similar but not identical sSMCs derived from chromosome 14. Methods: Conventional karyotype and MULTI-FISH. Results: +del(14)(q21.1) in the first case and +del(14)(q21.2) in the second. Conclusions: Constitutional partial trisomy 14 has an expanded clinical spectrum as one case from the literature was associated with gonadal tumor development. Similar cases, including the ones reported here, need to be carefully fo [...]

2166 11364

Open Access Review

Preimplantation Genetic Testing for HLA-matching: An Overview of Clinical Application and Utility

Received: 03 June 2019;  Published: 22 July 2019;  doi: 10.21926/obm.genet.1903084

Abstract

Preimplantation Genetic Testing for HLA-matching (PGT-HLA) has been one of the most controversial PGT applications, first reported in 2001. The procedure aims to identify an embryo that is not only healthy but also HLA-matched with a sibling in the family in need of haematopoietic stem cell transplantation (HSCT), considering that sibling HSCT stands the highest chance of success in comparison to alternative approaches. HLA-typing can be performed with or without PGT-M for the exclusion of a single-gene disorder. T [...]

2140 20199

Open Access Original Research

Genes Coding for GPI Biosynthesis in Pneumocystis Experienced Relaxed Selection: A Follow-up Study

Received: 05 May 2019;  Published: 11 July 2019;  doi: 10.21926/obm.genet.1903083

Abstract

Background: Phylogenetic analysis shows that Pneumocystis have coevolved with their mammalian hosts for millions of years. As a result, infection by Pneumocystis is species specific (i.e. a given Pneumocystis species can infect only a single species of host). This specificity suggests the existence of a Red-Queen dynamic between Pneumocystis and its host. Evidence of this dynamic is provided by the molecular diversity and the elevated rate of non-synonymous versus synonymous (dN/dS) codon substitutions among Pneumo [...]

2019 11513

Open Access Original Research

Individual Radiosensitivity in Lung Cancer Patients Assessed by G0 and Three Color Fluorescence in Situ Hybridization

Received: 27 July 2018;  Published: 26 June 2019;  doi: 10.21926/obm.genet.1902082

Abstract

Background: It is well known that radiosensitivity varies substantially from individual to individual. This may influence the tumor response and also cause side effects in normal tissues following the radiotherapy treatment for cancers. Therefore, we aimed to analyze the sensitivity of a lung cancer cohort to see whether patients display similar radiosensitivity distribution as compared to healthy individuals. Methods: Blood samples of healthy individuals (n = 244) and a small group of lung cancer patients (n= 38) [...]

2114 11381

Open Access Case Report

A De Novo Childhood Case of T-cell Lymphoblastic Leukemia with High Hyperdiploid Karyotype Carrying an Unreported Balanced Translocation t(X;5)(q26;q31.3~32) in A Male Patient

Received: 14 August 2018;  Published: 20 June 2019;  doi: 10.21926/obm.genet.1902081

Abstract

Background: The aggressive T-cell acute lymphoblastic leukemia (T-ALL) is one of the frequently occurring malignancies of the thymocytes. T-ALL is observed in 15% and 25% of all new diagnosed ALL cases in children and adults, respectively. Notably, T-ALL has a 3-fold higher incidence in males than in females. In nearly half of T-ALL cases, structural and/or numerical chromosomal abnormalities are detected, which have an important prognostic significance. A well-known genetic subtype of B-ALL, high hyperdiploidy (He [...]

2040 10625

Open Access Review

Airborne Interindividual Transmission of Pneumocystis jirovecii

Received: 17 December 2018;  Published: 22 May 2019;  doi: 10.21926/obm.genet.1902080

Abstract

Pneumocystis pneumonia (PCP) is the most frequent AIDS-defining disease among HIV-infected individuals in developed countries, and also affects immunocompromised non-HIV patients. Experimental studies on rodent models carried out in the early eighties have shown that Pneumocystis spp. can be transmitted via the airborne route. Unfortunately, this mode of acquisition and transmission has long been overlooked by physicians because PCP in immunosuppressed patients was considered to result from reactivation of a latent [...]

1975 10804

Open Access Review

The Changed Transcriptome of Muscular Dystrophy and Inflammatory Myopathy: Contributions of Non-Coding RNAs to Muscle Damage and Recovery

Received: 28 February 2019;  Published: 16 May 2019;  doi: 10.21926/obm.genet.1902079

Abstract

In order to successfully recover from damage, skeletal muscle tissue requires proper activation of a tightly orchestrated repair program. Non-coding RNAs actively participate in this complex process of demolition and rebuilding. In this review, the contribution of dysregulated non-coding RNA expression to disease-associated pathological changes is explored in hereditary muscular dystrophies and idiopathic inflammatory myopathies. Disturbances in spatiotemporal expression of non-coding RNAs appear to be key factors [...]

2114 9821

Open Access Review

Pneumocystis Species Co-evolution: State-of-the-Art Review

Received: 22 February 2019;  Published: 15 May 2019;  doi: 10.21926/obm.genet.1902078

Abstract

Pneumocystis spp. are a group of fungi that are known for causing opportunistic infections in immunocompromised individuals. It was only at the end of the 20th century that the scientific community challenged the notion of a unique species in the genus Pneumocystis (i.e., Pneumocystis carinii) that drastically changed the understanding of the natural history of pneumocystosis. It is now accepted that the Pneumocystis genus comprises a group of heterogenous fungi having multiple stenoxenic biological entities. These [...]

2077 11103

Open Access Case Report

Diagnosis of Fetal Kabuki Syndrome By Exome Sequencing Following Non-Specific Ultrasound Findings

Received: 11 March 2019;  Published: 15 May 2019;  doi: 10.21926/obm.genet.1902077

Abstract

Background: Fetal exome sequencing is becoming a crucial modality for genetic investigation whenever fetal malformations are documented in the context of normal chromosomal microarray analysis (CMA). When ultrasound findings are non-specific, the robustness of exome sequencing may be the only way to achieve a molecular diagnosis during pregnancy. Case: We describe a case of multiple non-specific fetal findings with the eventual diagnosis of fetal Kabuki Syndrome by exome sequencing. Conclusions: This case stresses [...]

2027 13628

Open Access Review

FISHing for Unstable Cellular Genomes in the Human Brain

Received: 06 February 2019;  Published: 30 April 2019;  doi: 10.21926/obm.genet.1902076

Abstract

The human brain has been repeatedly shown to exhibit intercellular/somatic genomic variations at the chromosomal level, which are involved in the neuronal diversity in health and disease. Brain-specific chromosomal mosaicism (aneuploidy) and chromosome instability play a role in the normal and pathological neurodevelopment, neurodegeneration and aging of the central nervous system. Regardless of achievements in somatic cell (single-cell) genomics, there is still no consensus on the amounts of chromosomally abnormal [...]

1760 9169

Open Access Editorial

Epigenetics is Here to Stay

Received: 24 April 2019;  Published: 30 April 2019;  doi: 10.21926/obm.genet.1902075

Abstract

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1466 7989

Open Access Review

Disturbed Ovarian Differentiation in XX;SRY-Negative Dogs

Received: 30 December 2018;  Published: 29 April 2019;  doi: 10.21926/obm.genet.1902074

Abstract

In a mammal, at the beginning of its development, the gonad is bipotential. The shift into a male or female pathway is coordinated by the sex chromosomal complement, which triggers a series of genetic pathways signaling the developmental pattern of the gonadal anlage. Being mutually exclusive, the differentiated gonad should be either a testis or an ovary. In females, the absence of SRY, a testis-determining gene, drives the signaling cascades controlling the ovarian differentiation. Albeit rare, disorders of the g [...]

2011 13996

Open Access Case Report

Fluorescence in Situ Hybridisation (FISH) is the First Tool to Identify Hypodiploidy in Paediatric Acute Lymphoblastic Leukaemia

Received: 24 December 2018;  Published: 17 April 2019;  doi: 10.21926/obm.genet.1902073

Abstract

Hypodiploidy has a low incidence in childhood acute lymphoblastic leukaemia (ALL). Patients are usually stratified into three subgroups, to allocate the correct treatment according to their ploidy level: high hypodiploidy (40-45 chromosomes), low hypodiploidy (33-39 chromosomes) and near haploidy (23-29 chromosomes). In this paper, a case is presented of near-haploid childhood ALL where fluorescence in situ hybridisation (FISH) provided an insight into the near-haploidy chromosomal aberration initially missed on ro [...]

1809 12728

Open Access Review

RNA Editors and DNA Mutators: Cancer Heterogeneity Through Sequence Diversification

Received: 03 December 2018;  Published: 08 April 2019;  doi: 10.21926/obm.genet.1902072

Abstract

Cancer development and progression is strongly associated with somatic mutations. From oncogenic hits that initiate the primary tumor formation to metastasis, the tumor mutational burden (TMB) plays a prominent role in the disease progression for the vast majority of cancer types. Not only are heterogeneous mutational loads or genetic heterogeneity causal to transcriptomic and proteomic discrepancies and to phenotypic diversity between individuals, they are also between tumor cells. But in addition to mutations, a [...]

1723 11456

Open Access Review

Molecular Mechanisms of Canine Cancers

Received: 30 January 2019;  Published: 01 April 2019;  doi: 10.21926/obm.genet.1902071

Abstract

Cancer is the leading cause of death in dogs, and 50 percent of dogs over the age of 10 develop cancer at some point. The most common cancers in dogs include lymphoma, mast cell tumors, osteosarcoma, mammary gland tumors, and melanoma, and many of them share marked similarities with their human counterparts. Although canines are afflicted with many of the same types of cancers as humans, the genetic basis behind these cancers are not as well understood. Thus, the aim of this study is to elucidate some of the molecu [...]

2234 16802

Open Access Review

The Role of Mitochondria in Oocyte and Early Embryo Health

Received: 01 January 2019;  Published: 29 March 2019;  doi: 10.21926/obm.genet.1901070

Abstract

The mitochondria of the oocyte are a prominent source of energy metabolism as well as mitochondrial DNA that will later populate the cells of the offspring. Recent discoveries provided new insight into the physiology of the mitochondria and its unique genetics. The concept of heteroplasmy defined as the presence of more than one type of mitochondrial genome, is gaining increasing recognition as an important contributor to several complex morbidities, age-related reproductive dysfunction and aging. Understanding the [...]

2755 28197

Open Access Opinion

Clonal Heterogeneity in Non-Small Cell Lung Cancer and the Possible Role in Predicting Response to Treatment with Immune Checkpoint Inhibitors

Received: 15 November 2018;  Published: 22 March 2019;  doi: 10.21926/obm.genet.1901069

Abstract

Immune oncology treatment with immune checkpoint inhibitors (ICIs) is revolutionizing therapeutic approach for advanced non-small cell lung cancer (NSCLC) patients, in terms of longer survival and improved quality of life. To date, the widely used and approved biomarker is programmed death ligand 1 (PD-L1) expression on tumour cells, but it is considered not accurate and it is more likely that many factors, related to both cancer and host, may better predict response to ICI. Among those factors, great attention is [...]

1808 9108

Open Access Review

FISH-Based Analysis of Mosaic Aneuploidy and Chromosome Instability for Investigating Molecular and Cellular Mechanisms of Disease

Received: 08 February 2019;  Published: 20 March 2019;  doi: 10.21926/obm.genet.1901068

Abstract

Recently, numerous studies have reported convincing data suggesting that chromosome instability may be not only a trigger of cancers but a possible mechanism for a wide spectrum of brain diseases. According to our original experience, chromosome instability is commonly observed during karyotyping of children with neuropsychiatric diseases and congenital malformations. To understand mechanisms of non-cancerous diseases potentially mediated by chromosome instability, which may represent an important target for molecu [...]

1876 10762

Open Access Technical Note

Interphase Quantitative Fluorescence in Situ Hybridization (IQ-FISH)

Received: 02 February 2019;  Published: 20 March 2019;  doi: 10.21926/obm.genet.1901067

Abstract

Fluorescence in situ hybridization (FISH) seems to be the most applicable and versatile molecular cytogenetic platform for visual interphase chromosome analysis offering a variety of opportunities for studying chromosomal structure and behaviour at the highest microscopic resolution and at all stages of the cell cycle. Quantitative assessment of FISH results has been repeatedly shown to increase the efficiency of FISH-based approaches. Here, we explore the potential of interphase quantitative FISH (IQ-FISH), which [...]

1896 11292

Open Access Research Article

New DNA Extraction Method for the Detection of Pneumocystis in Lung Tissue Samples of Colonized Individuals

Received: 30 January 2019;  Published: 18 March 2019;  doi: 10.21926/obm.genet.1901066

Abstract

Background: Pneumocystis jirovecii colonization in patients is associated with a low organism burden, which supports the need to use highly sensitive molecular techniques, such as nested-PCR to determine the presence of the organism. However, few studies have considered the effect of nucleic acid extraction methods on the detection of P. jirovecii. Here, we evaluate how pre-treatment affects microbial detection. Methods: Lung tissue samples from fifteen autopsied infants were processed using two different DNA extra [...]

1842 10745

Open Access Research Article

New Tools in Cognitive Neurobiology: Biotin-Digoxigenin Detection of Overlapping Active Neuronal Populations by Two-Color c-fos Compartment Analysis of Temporal Activity by Fluorescent in situ Hybridization (catFISH) and c-Fos Immunohistochemistry

Received: 12 October 2018;  Published: 04 March 2019;  doi: 10.21926/obm.genet.1901065

Abstract

Background: The method of cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH) is widely used in cellular and behavioral neurobiology. This technique exploits stimulus-induced expression of immediate early genes (IEGs) and allows identification of two neuronal populations activated in the brain of the same animal in response to neural or behavioral events separated by 25–30 min. The differential labeling is based on the visualization of nuclear RNA and cytoplasmic [...]

2562 17973

Open Access Research Article

COMBO-FISH: A Versatile Tool Beyond Standard FISH to Study Chromatin Organization by Fluorescence Light Microscopy

Received: 14 September 2018;  Published: 19 February 2019;  doi: 10.21926/obm.genet.1901064

Abstract

Background: Fluorescence In Situ Hybridization (FISH) has become routine for bio-medical research and medical diagnosis, thereby offering a variety of probes and ready-to-use kits that fulfil requirements for many applications. However, conventional FISH relies on chemical and/or thermal denaturation to improve target accessibility and uses huge amounts of DNA that needs to be bonded to the target site. COMBinatorial Oligo-nucleotide FISH (COMBO-FISH) offers possibilities to circumvent these shortcomings. Methods: [...]

2241 14808

Open Access Opinion

Interphase FISH: A Helpful Assay in Prenatal Cytogenetics Diagnosis

Received: 01 October 2018;  Published: 28 January 2019;  doi: 10.21926/obm.genet.1901063

Abstract

Since its introduction around the end of the 1970s, interphase fluorescence in situ hybridization (FISH) supports both classical and recent techniques for determining fetal karyotypes during prenatal diagnosis, quickly providing relevant information for the management of pregnancy. Interphase FISH plays an important role in the study of pregnancies with malformations, in mosaicism conditions, in confirming or excluding aneuploidy detected by non-invasive prenatal testing, and in the diagnosis of contiguous gene syn [...]

2441 24119

Open Access Technical Note

Repli-FISH (Fluorescence in Situ Hybridization): Application of 3D-(Immuno)-FISH for the Study of DNA Replication Timing of Genetic Repeat Elements

Received: 22 July 2018;  Published: 25 January 2019;  doi: 10.21926/obm.genet.1901062

Abstract

Background: Genetic repeat elements (interspersed or tandem repeats) have diverse functions within cells and at different phases of the cell cycle. However, their investigation at a genome-wide scale is challenging due to their repetitive nature. Here, we describe a method to study the DNA replication kinetics of different repeat elements in single cells throughout the S-phase of the cell cycle. Methods: Mouse major satellite, minor satellite and telomere repeat elements as well as human LINE-1 and Alu repeats were [...]

2276 766180

Open Access Short Report

The Usefulness of Preimplantation Genetic Testing for Chromosome Aneuploidy Informed by A Randomised Controlled Trial

Received: 29 October 2018;  Published: 22 January 2019;  doi: 10.21926/obm.genet.1901061

Abstract

United Kingdom guidelines recommend single embryo transfer (fresh or cryopreserved) in the first full assisted conception cycle for women under 40 years most at risk of having twins. Based on a recent randomized clinical trial for women aged 36 to 40 years, the hypothetical effect of preimplantation genetic testing for chromosome aneuploidy was extrapolated to single transfer of every morphologically transferable embryo available from a full cycle. Offering testing to every woman seems likely to result in fewer cli [...]

1706 9287

Open Access Review

Genotyping Pneumocystis jirovecii: Impacting Our Understanding of Interhuman Transmission

Received: 04 December 2018;  Published: 17 January 2019;  doi: 10.21926/obm.genet.1901060

Abstract

Pneumocystis jirovecii is an atypical fungus transmitted via the airborne route between humans. This fungus is exclusively associated with humans and almost each individual has encountered it at least once before reaching the age of two. P. jirovecii can be cleared and spontaneously resolutive in immunocompetent, whereas it can be responsible for severe Pneumocystis pneumonia (PCP) in immunocompromised patients. In the next decades, the putative increase of the population of immunocompromised patients is likely to [...]

1803 10930

Open Access Editorial

A Healthy and Happy 2019

Received: 15 January 2019;  Published: 15 January 2019;  doi: 10.21926/obm.genet.1901059

Abstract

A healthy and happy 2019

1025 6612

Open Access Review

Redirecting Fetal Programming: Evidence of Interventions that May Be A Tool for Health

Received: 01 June 2018;  Published: 28 December 2018;  doi: 10.21926/obm.genet.1804058

Abstract

Understanding the pathophysiology of disease can be an essential step to determining where and how to intervene for preventive or corrective health. Intrauterine growth restriction (IUGR) has been defined in livestock species as impaired gestational development of a fetus or its parts [1]. This broad category of ailments described by low fetal weight is accompanied by susceptibility to adult onset of chronic disease through fetal programming of numerous organ systems and their functions. This concern affects humans [...]

1844 10942

Open Access Review

Pneumocystis as a Co-Factor in Pulmonary Diseases

Received: 02 November 2018;  Published: 27 December 2018;  doi: 10.21926/obm.genet.1804057

Abstract

Pneumocystis causes life-threatening pneumonia in immunocompromised populations. More recently it has been implicated as a co-factor in a number of chronic lung diseases including chronic obstructive pulmonary disease (COPD), severe asthma, and cystic fibrosis (CF). In this review, we will examine the current literature regarding Pneumocystis and lung diseases in the HIV-infected patients and non-HIV immunocompromised populations, and the barriers to prophylaxis and treatment in these patients. Trimethoprim sulfame [...]

1860 9235

Open Access Review

Therapies for Childhood Polycystic Kidney Disease

Received: 07 August 2018;  Published: 23 December 2018;  doi: 10.21926/obm.genet.1804056

Abstract

Renal cysts are present in a wide variety of hereditary renal diseases in children. The term polycystic kidney disease (PKD) refers to two specific hereditary diseases, distinguished by the usual age of onset and genetic cause: autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF, MIM *606702) and autosomal dominant polycystic disease (ADPKD-OMIM *601313 and OMIM *173910). ARPKD/CHF is characterized by cystic dilations of the renal collecting ducts and developmental defects of biliar [...]

1973 12488

Open Access Review

Genetic and Epigenetic Regulation of Telomere Length: Current Findings, Methodological Limitations and Possibilities for Future Studies

Received: 29 October 2018;  Published: 19 December 2018;  doi: 10.21926/obm.genet.1804055

Abstract

Telomeres are TTAGGG repeats located at the end of chromosomes that maintain DNA stability. Telomere length (TL) has been widely implicated as a marker of biological age, and is associated with several human diseases, including depression, cardiovascular disease and cancer. Twin studies and cohort studies estimate heritability of TL between 78-82%. Moreover, several genomic loci which influence TL have been identified. Despite the success of genetic studies in furthering our understanding of telomere biology, ident [...]

2090 16862

Open Access Review

Distinct Mechanisms of Alterations in DNA Methylation/Demethylation Leading to Myelodysplastic Syndromes/Acute Myeloid Leukemia and Chronic Lymphocytic Leukemia

Received: 05 June 2018;  Published: 14 December 2018;  doi: 10.21926/obm.genet.1804054

Abstract

Epigenetic dysregulation is present in both myeloid and lymphoid disorders, with important differences reported between myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), on one hand, and chronic lymphocytic leukemia (CLL), on the other. Qualitative differences are reported in MDS/AML with gene fusions (e.g. TET1/LCX) and somatic mutations in epigenetic regulators (e.g. DNMT3A, TET2, IDH1/2), while differences in CLL are predominantly quantitative (e.g. DNMT3A, TET2). Indeed, and as supported by studies [...]

2357 13609

Open Access Original Research

Evaluation of Classical Statistical Methods for Analyzing BS-Seq Data

Received: 23 May 2018;  Published: 10 December 2018;  doi: 10.21926/obm.genet.1804053

Abstract

DNA methylation is an epigenetic change that is not only important in normal cell development, but also plays a significant role in human health and disease. Therefore, studies of DNA methylation have been actively pursued to clarify the precise role of this modification in disease etiology and its potential as a biomarker of disease. One key issue in analyzing DNA methylation data is the detection of significant differences in methylation levels between diseased individuals and healthy controls. In recent years, m [...]

2332 10163

Open Access Review

Reminiscence from Half a Century of Anti-Pneumocystis Drug Discovery and Development

Received: 12 September 2018;  Published: 06 December 2018;  doi: 10.21926/obm.genet.1804052

Abstract

My experiences with the identification and development of the anti-Pneumocystis drugs trimethoprim-sulfamethoxazole, dapsone and atovaquone are recounted. Attention is drawn to certain often-overlooked aspects of these drugs, including their concomitant effects against infections other than Pneumocystis, matters of dosing and adverse effects. During the past four decades several million people worldwide received chemoprophylaxis and treatment with these drugs for Pneumocystis jirovecii pneumonia. The population of [...]

1779 13904

Open Access Research Article

Assessment of Cytogenetic Abnormalities by FISH in Lymphocytes from a Victim Accidentally Exposed to Cobalt-60

Received: 14 August 2018;  Published: 25 November 2018;  doi: 10.21926/obm.genet.1804051

Abstract

Background: A radiation accident occurred on 14 June 2011 in an industrial facility in Bulgaria with a cobalt source (137 TBq) that was used to sterilize equipment. Five people received doses exceeding 1Gy, which led to the development of acute radiation syndrome. Biological dosimetry based on dicentric analysis was performed and the average acute whole-body doses estimated for the five patients ranged from 1.2 to 5.6 Gy. The purpose of this study was to evaluate induced chromosome aberrations in vivo four months af [...]

1620 8689

Open Access Case Report

Increased Recurrence Risk in Phelan-McDermid (22q13.3 Deletion) Syndrome: the Importance of FISH Demonstrated by a Case Series of Five Families

Received: 13 July 2018;  Published: 21 November 2018;  doi: 10.21926/obm.genet.1804050

Abstract

Background: Phelan-McDermid syndrome (PMS), or 22q13.3 deletion syndrome, is a neurodevelopmental disorder with an estimated prevalence of 1 in 10,000 to 1 in 20,000 newborns. Although it usually occurs de novo with a low recurrence risk, an increased recurrence risk is observed in some families. In this paper, we provide an overview of the underlying causes of increased recurrence risk in families with PMS and present a workflow aimed at identifying an increased recurrence risk. Methods: First, we report clinical [...]

2653 16046

Open Access Review

Pneumocystis jirovecii Pneumonia: Current Advances in Laboratory Diagnosis

Received: 21 August 2018;  Published: 13 November 2018;  doi: 10.21926/obm.genet.1804049

Abstract

Pneumocystis jirovecii pneumonia (PcP) remains a major cause of respiratory illness among immunocompromised patients. PcP is difficult to diagnose, in particular in non-HIV-infected patients, due to the lack of associated specific clinical data. Since P. jirovecii could not be cultivated for many years, microscopic visualization of cystic or trophic forms in respiratory specimens based on cytochemical or immunofluorescence staining are the standard procedure to identify this fungus. Polymerase chain reaction (PCR)- [...]

2143 22880

Open Access Review

Epigenetics and Infectious Disease: State-of-the-Art and Perspectives in New Generation Therapies

Received: 30 May 2018;  Published: 12 November 2018;  doi: 10.21926/obm.genet.1804048

Abstract

Infectious diseases are one of the most important causes of morbidity and mortality around the world and have a substantial impact on the health of communities. These diseases are caused by pathogenic microorganisms, such as bacteria, viruses, parasites and fungi. The antibiotics that are currently available are generally considered to be safe and well-tolerated. However antimicrobial resistance is an increasingly serious concern in the treatment of infectious diseases. An understanding of epigenetics now contribut [...]

1562 12647

Open Access Review

Epigenetic Regulation by Androgen Receptor in Prostate Cancer

Received: 26 May 2018;  Published: 02 November 2018;  doi: 10.21926/obm.genet.1804047

Abstract

Prostate cancer is the most common cancer among men in the world. Androgen receptor (AR), acting as a nuclear receptor, facilitates ligand-dependent transcriptional activation in the nucleus. Androgen deprivation therapy (ADT) is used for the treatment of advanced prostate cancer because androgen and AR signaling drive prostate tumor growth and anti-apoptotic function. Resistance to ADT in most tumors develops quickly; thus, AR continues to be active in relapsed tumors called castration-resistant prostate cancer (C [...]

2078 15737

Open Access Original Research

The Induction of Histone H3K4 Methylation on the SI Gene Correlates with SI mRNA Levels in Enterocyte-Like Caco-2 Cells

Received: 18 December 2017;  Published: 30 October 2018;  doi: 10.21926/obm.genet.1804046

Abstract

Background: Histone modifications, including acetylation and H3 lysine 4 (K4) methylation, are thought to be associated with transcriptional activation during differentiation. Methods: mRNA and histone modifications around the sucrase-isomaltase (SI) gene in Caco-2 cells (a small intestine cell line) during differentiation were determined by qRT-PCR and chromatin immunoprecipitation, respectively. Results: Mono-, di-, and tri-methylation of histone H3K4 on the SI gene correlated with the induction of SI gene expres [...]

1799 8484

Open Access Review

The Relationship between Pneumocystis Infection in Animal and Human Hosts, and Climatological and Environmental Air Pollution Factors: A Systematic Review

Received: 14 September 2018;  Published: 25 October 2018;  doi: 10.21926/obm.genet.1804045

Abstract

Background: Over the past decade, there has been rising interest in the interaction of Pneumocystis with the environment. This interest has arisen in part from the demonstration that environmental factors have important effects on the viability and transmission of microbes, including Pneumocystis. Environmental factors include climatological factors such as temperature, humidity, and precipitation, and air pollution factors including carbon monoxide, nitrogen dioxide, sulfur dioxide, and particulate matter. Methods [...]

2179 9538

Open Access Original Research

In Silico Detection and FISH Analysis to Determine Location of miRNAs in Solea senegalensis Chromosomes Using BACs

Received: 31 July 2018;  Published: 24 October 2018;  doi: 10.21926/obm.genet.1804044

Abstract

Background: MicroRNAs (miRNAs) are small, non-coding RNAs that play a very important role in gene expression by regulating mRNA cleavage and translation. The Senegalese sole, Solea senegalensis (Kaup 1858), is a flatfish species that shows great potential for marine aquaculture. Nevertheless, the existence of sexual dysfunction of males reared in captivity, high larval mortality, and diseases have hampered its production. The integration of sequence information with data on chromosomal physical location is useful f [...]

2197 10940

Open Access Research Article

Micronucleus-Centromere Assay to Measure Ionizing Radiation Damage of Low Dose Occupational Exposure

Received: 14 August 2018;  Published: 22 October 2018;  doi: 10.21926/obm.genet.1804043

Abstract

Background: The purpose of study was to assess the cytogenetic effect of chronic low dose radiation exposure of nuclear power plant workers using the micronucleus centromere assay. This method allows the differentiation between centromere-positive micronuclei containing whole chromosome and centromere-negative micronuclei containing acentric fragment pointing to clastogenic action of ionizing radiation. Methods: The effect of low dose occupational exposure was estimated in 32 nuclear power plant workers using in si [...]

1855 8903

Open Access Book Review

Applications of Fluorescence in Situ Hybridization in Radiation Cytogenetic Biodosimetry and Population Monitoring

Received: 26 August 2018;  Published: 19 October 2018;  doi: 10.21926/obm.genet.1804042

Abstract

The technique of in situ hybridization (ISH) using radioactively labeled DNA probes was first described in the late 1960s and early 1970s. The first use of fluorescence in situ hybridization (FISH) was reported in 1980s where RNA labeled with a fluorophore at the 3’ end was used to detect specific DNA sequences. Since then, the technique has undergone various modifications for detecting single genes, chromosomes and whole genomes on various targets such as interphase nucleus, prematurely condensed chromosomes [...]

2580 18123

Open Access Original Research

Evaluation of Recent Statistical Methods for Detecting Differential Methylation Using BS-seq Data

Received: 23 May 2018;  Published: 14 October 2018;  doi: 10.21926/obm.genet.1804041

Abstract

Whole genome profiling of differential DNA methylation between diseased and normal samples has significant implications in research to understand the role of epigenetic regulations of cells. In recent years, the development of bisulfite sequencing (BS-seq)-based molecular technology has enabled the measurement of DNA methylation at a nucleotide resolution throughout the genome. Given the availability of this new type of DNA methylation data, certain features challenge traditional analytical methods such as the Fish [...]

2361 12626

Open Access Review

Current Evidence on the Role of Epigenetic Mechanisms in Migraine: The Way Forward to Precision Medicine

Received: 09 May 2018;  Published: 10 October 2018;  doi: 10.21926/obm.genet.1804040

Abstract

Interactions between genetic and environmental factors in migraine are well known and can potentially determine an individual’s susceptibility to disease and responsiveness to treatment. Consequently, several epigenetic studies have been conducted to determine if and how genes are activated or inactivated in response to a diverse range of environmental migraine triggers. The results, in turn, have helped elucidate how these factors can promote or inhibit migraine progression or therapeutic response and can guide de [...]

2023 13985

Open Access Review

Deciphering the Epigenetic Landscape of Suicidal Behaviour: A Review of Current Findings, Caveats and Future Directions

Received: 20 June 2018;  Published: 06 October 2018;  doi: 10.21926/obm.genet.1804039

Abstract

Suicide is the second leading cause of death globally among young people and the tenth leading cause of death across all ages. Approximately 800,000 people die by suicide every year representing a significant global health burden. Despite this burden, the molecular pathology of suicide remains poorly understood. A number of recent studies have shown that epigenetic alterations are associated with suicidal behaviour. These epigenetic mechanisms, which act to regulate gene expression via modifications to DNA, histone [...]

2025 13364

Open Access Technical Note

Quality Assurance/Quality Control of Fluorescence in Situ Hybridization Tests in Hematologic Malignancies

Received: 22 July 2018;  Published: 03 October 2018;  doi: 10.21926/obm.genet.1804038

Abstract

Because of its’ simplicity, reliability and cost-effectiveness, fluorescence in situ hybridization (FISH) is a major technology that is widely applied in clinical diagnosis, especially for hematologic malignancies, even in the era of next-generation sequencing (NGS). In the Clinical Cytogenetics Laboratory at MD Anderson Cancer Center, over 15,000 FISH tests are performed each year, including approximately 1,000 BCR-ABL1 and 500 MYC FISH tests, respectively. In this chapter, we introduce the quality assurance/quali [...]

3137 20821

Open Access Original Research

Molecular Cytogenetic Characterization of Two Murine Colorectal Cancer Cell Lines

Received: 30 July 2018;  Published: 19 September 2018;  doi: 10.21926/obm.genet.1803037

Abstract

(1) Background: Colorectal cancer (CRC) is the third most common cancer in human and the fourth leading cause of adult man’s death. Murine tumor cell lines have been established as a model system for CRC, but their cytogenetic properties have so far been only poorly understood. (2) Methods: The two murine colon tumor cell lines CMT-93 and CT26 (also called CT26.WT, CT-26 or CT-26 WT) were investigated in this study by molecular cytogenetic methods, i.e. by multicolor-fluorescence in situ hybridization (mFISH), muri [...]

2818 16531

Open Access Review

Histone O-GlcNAcylation and Potential Biological Functions

Received: 05 July 2018;  Published: 17 September 2018;  doi: 10.21926/obm.genet.1803036

Abstract

Histone modifications play an important role in the control of DNA-based processes by altering the structure and function of chromatin. O-linked N-acetylglucosamine (O-GlcNAc) modification is a form of post-translational modification of proteins that affects the serine (Ser)/threonine (Thr) residues. This process is controlled by a single pair of enzymes, i.e. O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recent evidence indicates the existence of O-GlcNAc modification of histones, with 16 histone O-GlcNAc site [...]

2553 15639

Open Access Case Report

Identification of a Small Supernumerary Marker Chromosome Involving 11p14.1q12.1 in a Prenatal Case: Clinical and Molecular Characterization

Received: 30 May 2018;  Published: 16 September 2018;  doi: 10.21926/obm.genet.1803035

Abstract

Background: Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, and their characterization exclusively by banding cytogenetics is almost impossible. Multicolor fluorescence in situ hybridization approaches for their characterization are effective but expensive and time-consuming. Recently, the application of molecular karyotyping has resulted in improving the characterization of sSMC. Methods: Molecular karyotyping was used for the identification of a sSMC in this study. Results: In [...]

2244 11828

Open Access Editorial

Introduction to the Special Issue on Next Generation Sequencing: Short General Overview of NGS

Received: 14 August 2018;  Published: 13 September 2018;  doi: 10.21926/obm.genet.1803034

Abstract

he publication of the double helix DNA structure in 1953 [1] was the kick-off of numerous efforts to understand and unravel the complexity of the human genome. It took 50 years until the human genome project, based on Sanger sequencing, was completed in 2003 [2]. This was followed by what may be considered a revolution in the field of DNA analysis: the introduction of Next Generation Sequencing (NGS) in 2005 consisting of massively parallel sequencing of DNA fragments which allows the high throughput analysis of la [...]

1965 9017

Open Access Case Report

sSMC Characterization in a Male with Turner Syndrome Stigmata

Received: 23 March 2018;  Published: 07 September 2018;  doi: 10.21926/obm.genet.1803033

Abstract

Background: Small supernumerary marker chromosomes (sSMC) are rare cytogenetic findings in general, but especially in Turner syndrome so called sSMCT in a karyotype 46, X, +mar are even more scarce. According to the literature, sSMCT are derived from one of the Y-chromosomes in ~70% of the cases. Thus, to identify the presence of Y-chromosomal material is imperative, since these cases have an increased risk of gonadoblastoma deriving from the streak gonads. Methods: A 24-year-old short statured male presented with [...]

1831 9855

Open Access Review

Epigenetics of IgA Nephropathy: A Brief Review

Received: 27 May 2018;  Published: 06 September 2018;  doi: 10.21926/obm.genet.1803032

Abstract

Immunoglobin A Nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Its development is characterized by the deposition of immune complexes that consist of abnormally galactosylated IgA1 molecules and IgG or IgA autoantibodies in the mesangium and the subsequent induction of renal injury. Recent research has shed light to many aspects of the pathogenesis of the disease, including the contribution of epigenetic modifications in its onset and progression. This review aims to present some of the [...]

2049 10004

Open Access Review

Uniparental Disomy and Imprinting Disorders

Received: 28 June 2018;  Published: 30 August 2018;  doi: 10.21926/obm.genet.1803031

Abstract

Uniparental disomy (UPD), the inheritance of both homologues of a chromosome from only one parent, has been reported for nearly all human chromosomes. Depending on its mode of formation and time of occurrence, UPD can be present in all cells of an organism, or restricted to some cell lines as a mosaic UPD. Though its general frequency is unknown, it becomes clinically relevant when it produces homozygosity for recessive pathogenic variations or is associated with chromosomal imbalances. UPDs are well-known for thei [...]

3405 33575

Open Access Review

Prospects for Cure in Wilson Disease

Received: 18 July 2018;  Published: 22 August 2018;  doi: 10.21926/obm.genet.1803030

Abstract

Wilson Disease is a monogenetic disorder of copper metabolism affecting the ATP7B gene. Treatment is lifelong and focuses on removal of copper to arrest disease progression and improve the clinical manifestations of copper toxicity. Currently the only cure is liver transplantation, however, lifelong monitoring and immunosuppressive medications are still needed afterwards. The possibility of introducing functional ATP7B gene through gene therapy provides an exciting potential option for achieving a more permanent cu [...]

1864 11403

Open Access Original Research

New Insights into the Epigenetic Activities of Natural Compounds

Received: 30 May 2018;  Published: 16 August 2018;  doi: 10.21926/obm.genet.1803029

Abstract

Background: With their varied pharmacophores, natural products are interesting tools to open the drug discovery pipeline. Several plant secondary metabolites are components of the human diet and have reported epigenetic activities. In this study, we screened a small natural compound library for epigenetic activities. Methods: Seventy-one different natural products plus 17 controls collected from all collaborating laboratories were screened. Localized DNA methylation (DNAm) was studied on a stretch of the retinoic a [...]

2044 13415

Open Access Opinion

Runs of Homozygosity and Epigenetic Deregulation of Genomic Imprinting

Received: 29 May 2018;  Published: 15 August 2018;  doi: 10.21926/obm.genet.1803028

Abstract

Runs of homozygosity (ROH) are uninterrupted contiguous regions within the genome exhibiting allelic homozygosity (alleles are inherited from the same parent). Genome-wide analyses consistently demonstrate that megabase-scale ROH are ubiquitous in humans, reflecting individual demographic history. The number and length of ROH correlate increasingly with the degree of consanguinity and can be associated with genetic diseases in both inbred and outbred individuals. Genomic imprinting and uniparental disomy (UPD) are [...]

1914 9729

Open Access Original Research

Newborn Screening Programs: Next Generation Ethical and Social Issues

Received: 19 October 2017;  Published: 14 August 2018;  doi: 10.21926/obm.genet.1803027

Abstract

The benefits of neonatal screening programs are undeniable: children’s lives are saved, and disease burden and morbidity alleviated. Without a doubt, « classical » neonatal screening programs are in the best interests of newborns. Indeed, those screening programs are recognized among the ten most important public health achievements. However, newborn screening programs raise ethical, legal and social challenges. For example, which criteria should govern whether or not to include a disease in the list of screened co [...]

2180 16055

Open Access Original Research

Epigenetic Symmetry of DLGAP2: Pre-Implantation Maternal Methylation Switches to a Random Monoallelic Profile in Somatic Tissues

Received: 29 May 2018;  Published: 29 July 2018;  doi: 10.21926/obm.genet.1803026

Abstract

Background: Symmetrical DNA methylation profiles of autosomal genes are associated with equal expression by both alleles. Genes with an allelic imbalance or monoallelic expression are associated with discrete intervals of allele-specific methylation (ASM), as highlighted by genomic imprinting, X-chromosome inactivation and genotype-driven ASM. However, a more complex pattern has been described in which random monoallelic methylation provides cells with a unique mechanism for modulating allelic dosage. Methods: We c [...]

2225 16161

Open Access Review

Experimental DNA- or RNA-Directed Therapies for Trinucleotide Repeat Disease

Received: 17 April 2018;  Published: 27 July 2018;  doi: 10.21926/obm.genet.1803025

Abstract

Some repeats of three or more nucleotides in tandem, which are present in a gene or in its vicinity, tend to increase in number and for this reason are called dynamic mutations. These triplet repeats are unstable and can expand from one generation to the next. According to the expansion size, an unaffected individual can carry a pre-mutation that will expand through generations leading to the development of triplet repeat expansion diseases. The increase in the number of repeats over time leads to earlier developme [...]

2181 10044

Open Access Review

To Opt or Not to Opt for Preimplantation and/or Prenatal Genetic Testing?

Received: 05 June 2018;  Published: 23 July 2018;  doi: 10.21926/obm.genet.1803024

Abstract

Both preimplantation genetic testing (PGT) and prenatal diagnosis (PND) are powerful tools to tackle the transmission of inherited disorders carried by families from generation to generation. Here, we present an overview of the current landscape of both methods and identify the pros and cons of each of these reproductive options. In prenatal testing, non-invasive diagnostic methods have become available as an alternative for invasive diagnosis. Different genome sequencing strategies have now been introduced that en [...]

2026 10186

Open Access Review

Unusual Ways to Lose a Y Chromosome and Survive with Changed Autosomes: a Story of Mole Voles Ellobius (Mammalia, Rodentia)

Received: 16 May 2018;  Published: 22 July 2018;  doi: 10.21926/obm.genet.1803023

Abstract

Species of mole voles Ellobius demonstrate a broad variation in sex chromosomes and autosomes, which is unique among mammals. In four species, a Y chromosome was lost, and X0 or XX sex chromosomes in both sexes were obtained. The key testis-determining Sry (Sex-determining Region on Y) gene is absent in these species, and the regulation of its target, the Sox9 (SRY -box 9) gene, is questionable due to deletion in the key enhancer. In a single species, E. fuscocapillus, with routine XX-XY, the same deletion is prese [...]

2532 16910

Open Access Opinion

On Objectivity in Prenatal Genetic Care

Received: 16 April 2018;  Published: 12 June 2018;  doi: 10.21926/obm.genet.1802022

Abstract

We address an ongoing controversy over what health-care providers tell prospective parents about Down Syndrome (DS). Many parent, disability-rights, and anti-abortion activists believe that the messages that health-care professionals transmit to pregnant women and their partners are distorted. In their view, OB-GYNs, primary-care providers, clinical geneticists, midwives and other medical professionals generally assume that the quality of life for individuals with DS and their families is poor, whereas in fact, tho [...]

2099 11320

Open Access Technical Note

User-Friendly Approach to Gain Isolation of Interphase Cells for Fluorescence in Situ Hybridization

Received: 16 March 2018;  Published: 17 May 2018;  doi: 10.21926/obm.genet.1802021

Abstract

Background:Fluorescence in situ hybridization (FISH) can be performed on metaphase- and/or interphase cells. Metaphase cells can exclusively be obtained and studied after time-consuming cell culture. Therefore, this technique is suitable only for cells derived from peripheral blood, bone marrow or fibroblasts, the latter including skin, tumour or "prenatal tissues", such as the amnion or chorion. On the other hand, interphase cells can be gained from many different cells and even without cell culture. Methods:Here, [...]

1881 9998

Open Access Review

Non-Coding RNAs in Cutaneous Melanoma Development, Progression and Dissemination

Received: 13 March 2018;  Published: 15 May 2018;  doi: 10.21926/obm.genet.1802020

Abstract

Melanoma is a highly aggressive skin cancer with high incidence worldwide. There is growing evidence that aberrantly expressed non-coding RNAs (ncRNAs) play a role in the development, progression and dissemination of melanoma tumor cells. Among the many types of ncRNAs described in this review, the functions of micro- and long non-coding RNAs are described and related to the six hallmarks of cancer. Recently, ncRNAs discovered in body fluids have become known as one of the most promising groups of oncological bioma [...]

1986 9882

Open Access Concept Paper

German Guidelines for Molecular Genetic Diagnostic Testing Using High-throughput Technology, Such As Next-Generation Sequencing

Received: 24 September 2017;  Published: 28 April 2018;  doi: 10.21926/obm.genet.1802019

Abstract

On behalf of the German Society of Human Genetics, we present guidelines for molecular genetic diagnostic testing using high-throughput technology, such as next-generation sequencing (NGS). These guidelines have been formulated by an expert group and reviewed by members of the German Society of Human Genetics. Building on the existing EuroGentest guidelines for diagnostic NGS, these updated guidelines incorporate additional aspects and country-specific topics. New considerations include the introduction of a check [...]

2244 11543

Open Access Opinion

Moving Towards Routine Non-Invasive Prenatal Testing (NIPT): Challenges Related to Women’s Autonomy

Received: 10 February 2018;  Published: 19 April 2018;  doi: 10.21926/obm.genet.1802018

Abstract

Women’s reproductive autonomy, and its translation into informed free choice regarding prenatal screening, is a dominant concept in the bioethical discourse concerning prenatal screening. This discourse is based on the premise that access to information regarding the pregnancy promotes autonomous decision-making. However, studies show that the offer of prenatal screening as a routine part of pregnancy care is not supported, to a large degree, by appropriate informed consent mechanisms. This means that the implement [...]

2779 16552

Open Access Original Research

Identification and Prioritization of Causal Variants of Human Genetic Disorders from Exome or Whole Genome Sequencing Data

Received: 24 October 2017;  Published: 16 April 2018;  doi: 10.21926/obm.genet.1802017

Abstract

Background: With genome sequencing entering clinics as a diagnostic tool to detect genetic disorders, there is an increasing need for bioinformatics-based solutions that enable precise causal variant identification in a timely manner. Workflows for the identification of candidate disease-causing variants usually perform the following tasks: i) identification of variants; ii) filtering of variants to remove polymorphisms and technical artifacts; and iii) prioritization of remaining variants to provide a small set of [...]

2079 12349

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