by Parisa Gazerani

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

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 [...]

by Stefania Policicchio  , Emma L Dempster  and Therese M Murphy

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

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 [...]

by Zhenya Tang  , Jun Gu  , Guilin Tang  and L. Jeffrey Medeiros

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

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 [...]

by Hans Rhode  , Thomas Liehr  , Nadezda Kosyakova  , Martina Rinčić  and Shaymaa S. Hussein Azawi

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

(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 [...]

by Mitsuko Hirosawa  , Koji Hayakawa  , Kunio Shiota  and Satoshi Tanaka

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

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 [...]

by Maria Kontodiou  , Vassilis Paspaliaris  , Themistoklis Dagklis  , Elisavet Siomou  , Ahmed Hamid Al-Rikabi  , Kalliopi Tsita  , Theano Stavroulaki  , Andreas Pampanos  , Apostolos Zavlanos  , Georgios Papaioannou  , Ioannis Papoulidis  , Loretta Thomaidis  and Emmanouil Manolakos

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

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 [...]

by Ute Moog  and Domenico Coviello

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

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 [...]

by Frenny Sheth  , Thomas Liehr  , Kristin Mrasek  , Joris Andrieux  , Stuti Tewari  , Naznin Lubna  and Jayesh Sheth

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

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 [...]

by Stamatia Stai

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

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 [...]

by Thomas Eggermann  , Deborah J.G. Mackay  and Zeynep Tümer

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

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 [...]

by Michelle A. Camarata  , Uyen To  and Michael L. Schilsky

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

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 [...]

by Melita Vidakovic  , Jessica Marinello  , Maija Lahtela-Kakkonen  , Daumantas Matulis  , Vaida Linkuvienė  , Benoît Y. Michel  , Ruta Navakauskiene  , Michael S. Christodoulou  , Danielle Passarella  , Saulius Klimasauskas  , Christophe Blanquart  , Muriel Cuendet  , Judit Ovadi  , Stéphane Poulain  , Fabien Fontaine-Vive  , Alain Burger  and Nadine Martinet

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

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 [...]

by Ivan Y. Iourov  , Svetlana G. Vorsanova  and Yuri B. Yurov

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

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 [...]

by Karine Sénécal  , Brigid Unim  and Bartha Maria Knoppers

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

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 [...]

by Ana Monteagudo-Sánchez  , Marta Sánchez-Delgado  , Sonia Guara Ciurana  , Jose Medrano  , Maria Eugenia Poo-Llanillo  , Miho Ishida  , Gudrun E. Moore  , Isabel Iglesias-Platas  , Carlos Simón  and David Monk

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

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 [...]

by Inês Lopes Cardoso

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

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 [...]

by Joep Geraedts

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

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 [...]

by Irina Bakloushinskaya  and Sergey Matveevsky

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

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 [...]

by Diane B. Paul  and Ilana Löwy

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

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 [...]

by Thomas Liehr  , Monika Ziegler  , Nadezda Kosyakova  and Ahmed B.H. Al-Rikabi

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

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, [...]

by Virginie Vignard  and Delphine Fradin

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

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 [...]

by Peter Bauer  , Gabriele Wildhardt  , Dieter Gläser  , Clemens Müller-Reible  , Hanno J. Bolz  , Hanns-Georg Klein  , Ulrich Finckh  and Ute Hehr

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

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 [...]

by Stanislav Birko  , Marie-Eve Lemoine  , Minh Thu Nguyen  and Vardit Ravitsky

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

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 [...]

by Nagarajan Paramasivam  , Martin Granzow  , Christina Evers  , Katrin Hinderhofer  , Stefan Wiemann  , Claus R. Bartram  , Roland Eils  and Matthias Schlesner

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

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 [...]

by Eunise M. Aquino  , Miles C. Benton  , Larisa M. Haupt  , Heidi G. Sutherland  , Lyn R. Griffiths  and Rodney A. Lea

Received: 12 February 2018;  Published: 11 April 2018;  doi: 10.21926/obm.genet.1802016

DNA methylation involves the covalent transfer of a methyl group to the C-5 position of the cytosine ring on a DNA strand. DNA methylation is both heritable and modifiable and can affect gene expression. In recent years, epigenome-wide association studies using high-throughput technologies have associated variation in DNA methylation levels with normal and pathological aging processes in human populations. DNA methylation patterns have been used to construct epigenetic clocks which can serve as potential biomarkers [...]