scholarly journals Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction

2015 ◽  
Vol 112 (15) ◽  
pp. 4618-4623 ◽  
Author(s):  
Zhiyuan Chen ◽  
Darren E. Hagen ◽  
Christine G. Elsik ◽  
Tieming Ji ◽  
Collin James Morris ◽  
...  
Keyword(s):  
Bos Taurus ◽  
Reproductive Technologies ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
F1 Hybrid ◽  
Biallelic Expression ◽  
Loss Of Imprinting ◽  
Overgrowth Syndrome ◽  
Allele Specific

Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth syndrome Beckwith–Wiedemann (BWS). We have recently shown LOI at the KCNQ1 locus in LOS, the most common epimutation in BWS. Although the first case of ART-induced LOS was reported in 1995, studies have not yet determined the extent of LOI in this condition. Here, we determined allele-specific expression of imprinted genes previously identified in human and/or mouse in day ∼105 Bos taurus indicus × Bos taurus taurus F1 hybrid control and LOS fetuses using RNAseq. Our analysis allowed us to determine the monoallelic expression of 20 genes in tissues of control fetuses. LOS fetuses displayed variable LOI compared with controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. In addition, a positive correlation was observed between body weight and the number of biallelically expressed imprinted genes in LOS fetuses. Furthermore, not only was there loss of allele-specific expression of imprinted genes in LOS, but also differential transcript amounts of these genes between control and overgrown fetuses. In summary, we characterized previously unidentified imprinted genes in bovines and identified misregulation of imprinting at multiple loci in LOS. We concluded that LOS is a multilocus LOI syndrome, as is BWS.

209 Large Offspring Syndrome: Effects of in vitro Production on Embryo Epigenetics and Development

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 114-115
Author(s):  
Rocio Melissa Rivera
Keyword(s):  
Bos Taurus ◽  
Reproductive Technologies ◽  
Preimplantation Embryos ◽  
F1 Hybrids ◽  
Imprinted Genes ◽  
Abdominal Wall Defects ◽  
Biallelic Expression ◽  
Loss Of Imprinting ◽  
Micro Rnas ◽  
Skeletal Defects

Abstract In cattle, the use of assisted reproductive technologies (ART) can result in a congenital overgrowth condition known as large/abnormal offspring syndrome (LOS/AOS). The phenotypic characteristics of LOS include; somatic overgrowth, abdominal wall defects, large organs, breathing difficulties, skeletal defects, hypoglycemia, abnormal placentas, difficulty suckling, and perinatal death. LOS can have detrimental effects on the offspring and dam and also pose managerial and financial challenges to the producer. Research from the Rivera laboratory has demonstrated that LOS is an epigenetic syndrome. As in cattle, ART can promote the development of congenital overgrowth in humans, a condition known as Beckwith Wiedemann Syndrome (BWS). For the past 13 years, the Rivera laboratory has been characterizing LOS and we have shown that LOS and BWS are phenotypically and epigenotypically similar. In our studies, using gestation day ~105 Bos taurus taurus x Bos taurus indicus F1 hybrids, we showed global misregulation of imprinted and non-imprinted transcripts, micro RNAs and global misregulation of DNA methylation. In brief, LOS fetuses displayed variable loss-of-imprinting in kidney, liver, muscle and brain, when compared to controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. Not only was there loss of allele-specific expression of imprinted genes in LOS, but we also observed differential transcript amounts of these genes between control and overgrown fetuses. In addition, a positive correlation was observed between bodyweight and the number of biallelically expressed imprinted genes in LOS fetuses. From this work, we concluded that LOS is a multi-locus loss-of-imprinting condition. Current work, aims to determine if LOS is identifiable during pregnancy using day 55 fetal ultrasonography and day 55 and 105 maternal blood. In addition, we aim to determine how serum supplementation of culture medium can program preimplantation embryos to develop LOS. Findings will be discussed.

scholarly journals Bumblebee worker castes show differences in allele-specific DNA methylation and allele-specific expression

2020 ◽  
Author(s):  
H. Marshall ◽  
A.R.C. Jones ◽  
Z.N. Lonsdale ◽  
E.B. Mallon
Keyword(s):  
Dna Methylation ◽  
Bombus Terrestris ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Genome Wide ◽  
Expression Bias ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Worker Castes

AbstractAllele-specific expression is when one allele of a gene shows higher levels of expression compared to the other allele, in a diploid organism. Genomic imprinting is an extreme example of this, where some genes exhibit allele-specific expression in a parent-of-origin manner. Recent work has identified potentially imprinted genes in species of Hymenoptera. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals DNA methylation is often associated with imprinted genes. DNA methylation systems have been described in species of Hymenoptera, providing a candidate imprinting mechanism. Using previously generated RNA-Seq and whole genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive castes and the proportion of allele-specific expression bias generally varies between colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both castes. There is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that DNA methylation does not directly drive genome-wide allele-specific expression in this species. Only a small number of the genes identified may be ‘imprinted’ and it may be these genes which are associated with allele-specific DNA methylation. Future work utilising reciprocal crosses to identify parent-of-origin DNA methylation will further clarify the role of DNA methylation in parent-of-origin allele-specific expression.

scholarly journals Allele specific expression in worker reproduction genes in the bumblebee Bombus terrestris

2015 ◽  
Author(s):  
Harindra E Amarasinghe ◽  
Bradley J Toghill ◽  
Despina Nathanael ◽  
Eamonn B Mallon
Keyword(s):  
Bombus Terrestris ◽  
Expression Patterns ◽  
Worker Reproduction ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

Methylation has previously been associated with allele specific expression in ants. Recently, we found methylation is important in worker reproduction in the bumblebee Bombus terrestris. Here we searched for allele specific expression in twelve genes associated with worker reproduction in bees. We found allele specific expression in Ecdysone 20 monooxygenase and IMP-L2-like. Although we were unable to confirm a genetic or epigenetic cause for this allele specific expression, the expression patterns of the two genes match those predicted for imprinted genes.

scholarly journals Allele specific expression in worker reproduction genes in the bumblebee Bombus terrestris

2015 ◽  
Author(s):  
Harindra E Amarasinghe ◽  
Bradley J Toghill ◽  
Despina Nathanael ◽  
Eamonn B Mallon
Keyword(s):  
Bombus Terrestris ◽  
Expression Patterns ◽  
Worker Reproduction ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

Methylation has previously been associated with allele specific expression in ants. Recently, we found methylation is important in worker reproduction in the bumblebee Bombus terrestris. Here we searched for allele specific expression in twelve genes associated with worker reproduction in bees. We found allele specific expression in Ecdysone 20 monooxygenase and IMP-L2-like. Although we were unable to confirm a genetic or epigenetic cause for this allele specific expression, the expression patterns of the two genes match those predicted for imprinted genes.

239 ALLELE-SPECIFIC EXPRESSION OF X CHROMOSOME-LINKED GENE MAO-A DURING PRE-IMPLANTATION DEVELOPMENT IN BOVINE EMBRYO

2010 ◽  
Vol 22 (1) ◽  
pp. 277
Author(s):  
A. R. Ferreira ◽  
G. M. Machado ◽  
T. O. Diesel ◽  
J. O. Carvalho ◽  
R. Rumpf ◽  
...  
Keyword(s):  
X Chromosome ◽  
Bos Taurus ◽  
Paternal Allele ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
X Chromosomes ◽  
Linked Gene ◽  
Mao A ◽  
Allele Specific

The in vitro embryo culture might affect epigenetic mechanisms, which are involved in controlling the expression of genes related to embryonic development and inactivation of X chromosome. Female mammals have 2 X chromosomes, and males have only 1. This has led to a particular mechanism of evolution of dosage compensation, called X-chromosome inactivation, an important epigenetic event that must occur in all mammalian female embryos. During embryogenesis, at the late blastocyst development (Xue F et al. 2002 Nature Genet. 31, 216–220), 1 of the 2 X chromosomes is randomly inactivated in each cell of the inner cell mass and preferentially X paternal in trophoblast. The aim of this study was to characterize the allele-specific expression of the X chromosome-linked gene monoamine oxidase type A (MAO-A) during in vitro pre-implantation embryo development in bovine. For phenotyping of the MAO-A gene, the RT-PCR restriction fragment length polymorphism technique was used. Primers were designed flanking a single nucleotide polymorphism and the sequence of forward inner primer creating a site of restriction to the RsaI enzyme, thus allowing the detection of allele-specific expression (Bos taurus Taurus × Bos taurus indicus). Oocytes were aspirated from 9 Nelore heifers homozygous for theA allele previously genotyped. The oocytes were selected, matured in vitro, and inseminated with X-sorted sperm from a Holstein bull homozygous for the G allele. Two pools of 10 heterozygous in vitro embryos of each developmental stage, 4-cell [44 h post-insemination (p.i.)], 8- to 16-cell (72 h p.i.), morula (144 h p.i.), blastocyst (156 p.i.), and expanded blastocyst (168 h p.i.), were produced and frozen until RNA extraction. Total RNA was extracted using Invisorb® Spin Cell RNA Mini Kit (Invitek, Berlin, Germany) according to the manufacturer’s protocol, and residual genomic DNA was removed with DNase I treatment. cDNA was done using Oligo dT primers (Invitrogen) and superscript III reverse transcriptase (Invitrogen). Nested PCR for each pool was performed and then the amplicons were digested with 10 U of RsaI enzyme (Promega, Madison, WI, USA). The products were separated by electrophoresis on a 3% agarose gel stained with ethidium bromide. The results showed that both alleles were expressionally represented in the 4-cell, 8- to 16-cell, and expanded blastocyst stages, with the X paternal allele disappearing in morula and blastocyst. We can conclude that both, maternal and paternal X chromosomes, are activated in the 2 earliest stages, inactivated in the morula and blastocyst stages, and reactivated in the expanded blastocyst stage. This research was supported by Embrapa Genetic Resources and Biotechnology and the Brazilian National Council for Scientific and Technological Development (CNPq).

scholarly journals Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antoine Hoguin ◽  
Achal Rastogi ◽  
Chris Bowler ◽  
Leila Tirichine
Keyword(s):  
Phaeodactylum Tricornutum ◽  
Protein Transport ◽  
Natural Hybridization ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Biallelic Expression ◽  
Allele Specific

AbstractRecent advances in next generation sequencing technologies have allowed the discovery of widespread autosomal allele-specific expression (aASE) in mammals and plants with potential phenotypic effects. Extensive numbers of genes with allele-specific expression have been described in the diatom Fragilariopsis cylindrus in association with adaptation to external cues, as well as in Fistulifera solaris in the context of natural hybridization. However, the role of aASE and its extent in diatoms remain elusive. In this study, we investigate allele-specific expression in the model diatom Phaeodactylum tricornutum by the re-analysis of previously published whole genome RNA sequencing data and polymorphism calling. We found that 22% of P. tricornutum genes show moderate bias in allelic expression while 1% show nearly complete monoallelic expression. Biallelic expression associates with genes encoding components of protein metabolism while moderately biased genes associate with functions in catabolism and protein transport. We validated candidate genes by pyrosequencing and found that moderate biases in allelic expression were less stable than monoallelically expressed genes that showed consistent bias upon experimental validations at the population level and in subcloning experiments. Our approach provides the basis for the analysis of aASE in P. tricornutum and could be routinely implemented to test for variations in allele expression under different environmental conditions.

scholarly journals Allele-specific expression of imprinted genes in mouse migratory primordial germ cells

2002 ◽  
Vol 115 (1-2) ◽  
pp. 157-160 ◽  
Author(s):  
Piroska E. Szabó ◽  
Karin Hübner ◽  
Hans Schöler ◽  
Jeffrey R. Mann
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific
Sign in / Sign up

Export Citation Format

Share Document