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; but its most prominent fea [...]

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 replacement of ATP7B in hepatocytes by liver transplantation, however, lifelong monitoring and immunosuppressive medications are still needed. The possibility of introducing functional ATP7B gene through gene therapy provides an exciting potential option for [...]

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 belong to our diet and have conflictual documented epigenetic activities which need clarification. Methods: Seventy-one different natural products plus 17 controls were assembled for screening. First localized DNA methylation (DNAm) was studied on a stretch of the Retinoic Acid Receptor geneRAR followed then by a wider measure of all genomic 5 methylat [...]

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 continuous regions within the genome exhibiting allelic homozygosity (identical alleles are inherited from each parent). Genome-wide analyses consistently evidence that megabase-scale ROH are ubiquitous in humans reflecting individual demographic history. The number and length of ROH increasingly correlate with degree of consanguinity and are likely to be associated with genetic diseases both in inbred and outbred individuals. It is noteworthy that there are two other ph [...]

by Karine Sénécal  , Brigid Unim  and Bartha Maria Knoppers

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

Although newborn screening programs are among the ten most important public health achievements, a number of ethical, legal and social issues have emerged. Notably, the number of diseases screened; consent and notification processes; sample, retention; and potentially secondary use of residual blood spots are now contested. In addition, newborn screening programs are also facing one of the biggest challenges, the arrival of next-generation sequencing technologies, such as whole genome sequencing. The key ethical, l [...]

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 Symmetric DNA methylation profiles of autosomal genes is associated with equal expression from 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 a unique mechanism for modulating allelic dosage. - Methods We comb [...]

by Inês Lopes Cardoso

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

Dynamic mutations involve expansion of the number of repeat units consisting of three or more nucleotides in tandem (i.e., adjacent to one another), present in a gene or in its neighborhood. Depending on expansion size, unaffected individuals can be carriers of a pre-mutation. Instability of triplet repeats can lead to gradual expansion through generations and accumulation of a certain number of repeats can lead to the consequent development of disease. The increase in the number of triplet repeats from one generat [...]

by Joep Geraedts

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

Both preimplantation genetic testing and prenatal testing are powerful tools to tackle the transmission of inherited disorders in families carrying the diseases from generation to generation. This article presents an overview of the current landscape of both methods and identifies the pros and cons of each of these reproductive options.

by Irina Bakloushinskaya  and Sergey Matveevsky

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

When does reproduction start? An old question of the chicken and the egg is even more complicated in relation to mole voles Ellobius. First, ‘chicken’ should be a female, and males are obviously involved in reproduction too because zygote is a result of sperm and oocyte fusion. But nobody knows how males appear in Ellobius lacking the Y chromosome and key testis-determining Sry gene (X0♂/X0♀ or XX♂/XX♀). Second, it is unclear, how balanced gametes form in complex heterozygous hybrids, whose parents carry Robertsoni [...]

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). In the view of critics, including many parent, disability-rights, and anti-abortion activists, the messages that health-care professionals transmit to pregnant women and their partners are distorted. OB-GYNs, primary-care providers, clinical geneticists, midwives and other medical professionals generally believe that the quality of life for individuals with DS and their families is poor. The critics [...]