Parent of origin DNA methylation as a potential mechanism for genomic imprinting in bees.

Genomic imprinting is defined as parent-of-origin allele-specific expression. In order for genes to be expressed in this manner an `imprinting' mark must be present to distinguish the parental alleles within the genome. In mammals imprinted genes are primarily associated with DNA methylation. Genes exhibiting parent-of-origin expression have recently been identified in two species of Hymenoptera with functional DNA methylation systems; Apis mellifera and Bombus terrestris. We carried out whole genome bisulfite sequencing of parents and offspring from reciprocal crosses of two B. terrestris subspecies in order to identify parent-of-origin DNA methylation. We were unable to survey a large enough proportion of the genome to draw a conclusion on the presence of parent-of-origin DNA methylation however we were able to characterise the sex- and caste-specific methylomes of B. terrestris for the first time. We find males differ significantly to the two female castes, with differentially methylated genes involved in many histone modification related processes. We also analysed previously generated honeybee whole genome bisulfite data to see if genes previously identified as showing parent-of-origin DNA methylation in the honeybee show consistent allele-specific methylation in independent data sets. We have identified a core set of 12 genes in female castes which may be used for future experimental manipulation to explore the functional role of parent-of-origin DNA methylation in the honeybee. Finally, we have also identified allele-specific DNA methylation in honeybee male thorax tissue which suggests a role for DNA methylation in ploidy compensation in this species.

The lose-to-win strategy of the weak: intraspecific parasitism via egg abduction in a termite

Predation by larger conspecifics poses a major threat to small juveniles in many animal species. However, in social insects, raids perpetrated by large colonies may provide smaller colonies with opportunities for parasitization. Herein, in the termite Reticulitermes speratus , we demonstrate that small incipient colonies parasitize large mature colonies through egg abduction when attacked by raiding conspecifics. We observed that the eggs of incipient colonies were brought into raiding colonies while their parents were killed during the attack. In this species, unmated females found new colonies with female–female (FF) cooperation, in addition to the typical monogamous colony foundation. Interestingly, the abducted eggs of FF pairs developed into nymphs (reproductive caste) in the raiding colonies, whereas the eggs of male–female (MF) pairs developed into workers (non-reproductive caste). Parthenogenetic eggs are known to be developmentally predisposed to becoming female reproductives owing to genomic imprinting in termites. This study demonstrates that the plundering of small colonies by larger conspecific colonies not only results in the extinction of the weaker colonies, but also serves as a strategy that incipient colonies use to obtain the reproductive position in large colonies by stealth. The results elucidate the diversity and complexity of inter-colonial interactions in social insects.

Epigenetic modifications potentially controlling the allelic expression of imprinted genes in sunflower endosperm

Background Genomic imprinting is an epigenetic phenomenon mainly occurs in endosperm of flowering plants. Genome-wide identification of imprinted genes have been completed in several dicot Cruciferous plant and monocot crops. Results Here, we analyzed global patterns of allelic gene expression in developing endosperm of sunflower which belongs to the composite family. Totally, 691 imprinted loci candidates were identified in 12 day-after-pollination sunflower endosperm including 79 maternally expressed genes (MEG) and 596 paternally expressed genes (PEG), 6 maternally expressed noncoding RNAs (MNC) and 10 paternally expressed noncoding RNAs (PNC). And a clear clustering of imprinted genes throughout the rapeseed genome was identified. Generally, imprinting in sunflower is conserved within a species, but intraspecific variation also was detected. Limited loci in sunflower are imprinted in other several different species. The DNA methylation pattern around imprinted genes were investigated in embryo and endosperm tissues. In CG context, the imprinted genes were significantly associated with differential methylated regions exhibiting hypomethylation in endosperm and hypermethylation in embryo, which indicated that the maternal demethylation in CG context potentially induce the genomic imprinting in endosperm. Conclusion Our study would be helpful for understanding of genomic imprinting in plants and provide potential basis for further research in imprinting in sunflower.

Case Studies of Two Classical Imprinting Growth Disorders: Silver–Russell and Beckwith–Wiedemann Syndromes

The genetic influences on human growth are being increasingly deciphered. Silver–Russell and Beckwith–Wiedemann syndromes (SRS; BWS) are two relatively common genetic syndromes with under- and overgrowth-related issues being the reason for referral. Aberration in genomic imprinting is the underlying genetic pathomechanism behind these syndromes. Herein, we described a series of children with these two growth disorders and give an orientation to the reader of the concept of imprinting as well as the genetic testing strategy and counseling to be offered in these syndromes.

Asynchronous Replication Timing: A Mechanism for Monoallelic Choice During Development

Developmental programming is carried out by a sequence of molecular choices that epigenetically mark the genome to generate the stable cell types which make up the total organism. A number of important processes, such as genomic imprinting, selection of immune or olfactory receptors, and X-chromosome inactivation in females are dependent on the ability to stably choose one single allele in each cell. In this perspective, we propose that asynchronous replication timing (ASRT) serves as the basis for a sophisticated universal mechanism for mediating and maintaining these decisions.

DNA Methylation Dynamics in the Female Germline and Maternal-Effect Mutations That Disrupt Genomic Imprinting

Genomic imprinting is an epigenetic marking process that results in the monoallelic expression of a subset of genes. Many of these ‘imprinted’ genes in mice and humans are involved in embryonic and extraembryonic growth and development, and some have life-long impacts on metabolism. During mammalian development, the genome undergoes waves of (re)programming of DNA methylation and other epigenetic marks. Disturbances in these events can cause imprinting disorders and compromise development. Multi-locus imprinting disturbance (MLID) is a condition by which imprinting defects touch more than one locus. Although most cases with MLID present with clinical features characteristic of one imprinting disorder. Imprinting defects also occur in ‘molar’ pregnancies-which are characterized by highly compromised embryonic development-and in other forms of reproductive compromise presenting clinically as infertility or early pregnancy loss. Pathogenic variants in some of the genes encoding proteins of the subcortical maternal complex (SCMC), a multi-protein complex in the mammalian oocyte, are responsible for a rare subgroup of moles, biparental complete hydatidiform mole (BiCHM), and other adverse reproductive outcomes which have been associated with altered imprinting status of the oocyte, embryo and/or placenta. The finding that defects in a cytoplasmic protein complex could have severe impacts on genomic methylation at critical times in gamete or early embryo development has wider implications beyond these relatively rare disorders. It signifies a potential for adverse maternal physiology, nutrition, or assisted reproduction to cause epigenetic defects at imprinted or other genes. Here, we review key milestones in DNA methylation patterning in the female germline and the embryo focusing on humans. We provide an overview of recent findings regarding DNA methylation deficits causing BiCHM, MLID, and early embryonic arrest. We also summarize identified SCMC mutations with regard to early embryonic arrest, BiCHM, and MLID.

Canonical and Non-canonical Genomic Imprinting in Rodents

Genomic imprinting is an epigenetic phenomenon that results in unequal expression of homologous maternal and paternal alleles. This process is initiated in the germline, and the parental epigenetic memories can be maintained following fertilization and induce further allele-specific transcription and chromatin modifications of single or multiple neighboring genes, known as imprinted genes. To date, more than 260 imprinted genes have been identified in the mouse genome, most of which are controlled by imprinted germline differentially methylated regions (gDMRs) that exhibit parent-of-origin specific DNA methylation, which is considered primary imprint. Recent studies provide evidence that a subset of gDMR-less, placenta-specific imprinted genes is controlled by maternal-derived histone modifications. To further understand DNA methylation-dependent (canonical) and -independent (non-canonical) imprints, this review summarizes the loci under the control of each type of imprinting in the mouse and compares them with the respective homologs in other rodents. Understanding epigenetic systems that differ among loci or species may provide new models for exploring genetic regulation and evolutionary divergence.

Genetic forms of developmental delay and intellectual disability in the practice of the medical genetic consultation of Research Centre for Medical Genetics

Задержка психического развития (ЗПР) и умственная отсталость (УО) являются частыми причинами направления пациентов на медико-генетическое консультирование. Наблюдаемый в последние годы значительный рост числа нозологических форм моногенных и хромосомных болезней среди пациентов с ЗПР или УО медико-генетической консультации Медико-генетического научного центра отражает повышение эффективности диагностики наследственных форм данной патологии. Цели исследования: оценка долей клинически и/или лабораторно подтвержденных хромосомных, моногенных заболеваний и болезней геномного импринтинга, диагностированных у пациентов с ЗПР или УО; определение эффективности разных методов диагностики генетических форм ЗПР и УО; расчет сегрегационной частоты для оценки вклада моногенных форм с аутосомно-рецессивным и X-сцепленным рецессивным типами наследования в недифференцированные ЗПР и УО. Выборка включала 2350 пациентов с ЗПР или УО различных степеней тяжести и пациентов с диагнозом, предполагающим развитие ЗПР или УО по мере взросления, проконсультированных врачами-генетиками консультативного и научно-консультативного отделов Медико-генетического научного центра им. Бочкова в 2006, 2007, 2016 гг. и первой половине 2017 г. В исследуемый период (2006, 2007, 2016 и первая половина 2017 г.) отмечается тенденция к снижению доли хромосомной патологии среди всех пациентов выборки. В группе пациентов с ЗПР или УО с аномалиями хромосом с течением времени отмечается значительный рост доли структурной хромосомной патологии и снижение доли заболеваний, обусловленных изменением числа хромосом. Доля моногенных форм остается практически неизменной в исследуемый период. Внутри данной группы отмечается некоторый рост доли аутосомно-доминантной патологии. Доля пациентов с ЗПР или УО, обусловленных болезнями геномного импринтинга, достоверно различается в исследуемые годы, со временем отмечается тенденция к ее уменьшению. Доля только клинически установленных синдромов без лабораторного подтверждения значительно снижается в исследуемый период. Максимальная диагностическая эффективность среди лабораторных генетических методов показана для микросателлитного анализа, MLPA, хромосомного микроматричного анализа и секвенирования нового поколения. Developmental delay (DD) and intellectual disability (ID) are frequent reasons for referring patients for medical genetic counseling. A significant increase in the number of nosological forms of monogenic and chromosomal diseases among patients with DD or ID in medical genetic consultation of Bochkov Research Centre for Medical Genetics in recent years reflects an increase in its effectiveness in diagnosing this pathology. Purpose of the research: 1. To estimate the proportion of clinically and/or laboratory-confirmed chromosomal, monogenic, and genomic imprinting disorders diagnosed in patients with DD or ID consulted by geneticists from the consultation and scientific consulting departments of the Bochkov Research Centre for Medical Genetics in 2006, 2007, 2016, and the first half of 2017. 2. Determination of the effectiveness of different diagnostic methods of genetic forms DD and ID. 3. Calculation of segregation frequency to estimate the contribution of monogenic forms with autosomal recessive and X-linked recessive types of inheritance among undifferentiated cases of DD and ID. The sampling for the analysis included 2350 patients with DD or ID of varying severity, as well as patients with a diagnosis suggesting the development of DD or ID as they mature, consulted by geneticists from the consultation and scientific consulting departments of the Bochkov Research Centre for Medical Genetics in 2006, 2007, 2016, and the first half of 2017. During the research period (2006, 2007, 2016, and the first half of 2017), there was a decreasing trend in the proportion of chromosomal pathology among all patients of the sampling. Within the group of patients with DD or ID with chromosomal pathology, a significant increase in the proportion of structural chromosomal pathology and a decrease in the proportion of diseases caused by changes in the number of chromosomes is noted over time. The proportion of monogenic forms remains practically unchanged during the study period. Within this group, there is some increase in the share of AD pathology. The proportion of patients with DD or ID caused by genomic imprinting disorders varies significantly in the years studied, with a tendency to decrease over time. The proportion of only clinically identified syndromes without laboratory confirmation decreases significantly during the study period. The maximum diagnostic efficiency among laboratory genetic methods has been shown for microsatellite analysis, MLPA, chromosomal microarray analysis (CMA) and next generation sequencing (NGS).

Environmental Exposure to Endocrine Disrupting Chemicals Influences Genomic Imprinting, Growth, and Metabolism

Genomic imprinting is an epigenetic mechanism that results in monoallelic, parent-of-origin-specific expression of a small number of genes. Imprinted genes play a crucial role in mammalian development as their dysregulation result in an increased risk of human diseases. DNA methylation, which undergoes dynamic changes early in development, is one of the epigenetic marks regulating imprinted gene expression patterns during early development. Thus, environmental insults, including endocrine disrupting chemicals during critical periods of fetal development, can alter DNA methylation patterns, leading to inappropriate developmental gene expression and disease risk. Here, we summarize the current literature on the impacts of in utero exposure to endocrine disrupting chemicals on genomic imprinting and metabolism in humans and rodents. We evaluate how early-life environmental exposures are a potential risk factor for adult metabolic diseases. We also introduce our mouse model of phthalate exposure. Finally, we describe the potential of genomic imprinting to serve as an environmental sensor during early development and as a novel biomarker for postnatal health outcomes.