Autosomal monoallelic expression: genetics of epigenetic diversity?

Ecological adaptation plays an important role in the process of plant expansion, and genetics and epigenetics are important in the process of plant adaptation. In this study, genetic and epigenetic analyses and soil properties were performed on D. angustifolia of 17 populations, which were selected in the tundra zone on the western slope of the Changbai Mountains. Our results showed that the levels of genetic and epigenetic diversity of D. angustifolia were relatively low, and the main variation occurred among different populations (amplified fragment length polymorphism (AFLP): 95%, methylation sensitive amplification polymorphism (MSAP): 87%). In addition, DNA methylation levels varied from 23.36% to 35.70%. Principal component analysis (PCA) results showed that soil properties of different populations were heterogeneous. Correlation analyses showed that soil moisture, pH and total nitrogen were significantly correlated with genetic diversity of D. angustifolia, and soil temperature and pH were closely related to epigenetic diversity. Simple Mantel tests and partial Mantel tests showed that genetic variation significantly correlated with habitat or geographical distance. However, the correlation between epigenetic variation and habitat or geographical distance was not significant. Our results showed that, in the case of low genetic variation and genetic diversity, epigenetic variation and DNA methylation may provide a basis for the adaptation of D. angustifolia.

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Somatotroph Tumors and the Epigenetic Status of the GNAS Locus

International Journal of Molecular Sciences ◽

10.3390/ijms22147570 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7570

Author(s):

Pauline Romanet ◽

Justine Galluso ◽

Peter Kamenicky ◽

Mirella Hage ◽

Marily Theodoropoulou ◽

...

Keyword(s):

Genomic Analysis ◽

Somatostatin Analogues ◽

Differentially Methylated Region ◽

Monoallelic Expression ◽

Lower Sensitivity ◽

Biallelic Expression ◽

Expression Levels ◽

Methylation Index ◽

Significant Difference ◽

Gsp Oncogene

Background: Forty percent of somatotroph tumors harbor recurrent activating GNAS mutations, historically called the gsp oncogene. In gsp-negative somatotroph tumors, GNAS expression itself is highly variable; those with GNAS overexpression most resemble phenotypically those carrying the gsp oncogene. GNAS is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in GNAS imprinting of gsp-negative tumors affect GNAS expression levels and tumorigenesis. Methods: We characterized the GNAS locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Results: Multi-omics analysis of the first cohort identified a significant difference between gsp-negative and gsp-positive tumors in the methylation index at the known differentially methylated region (DMR) of the GNAS A/B transcript promoter, which was confirmed in the larger series of 82 tumors. GNAS allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous gsp-negative tumors. GNAS expression was significantly reduced in the 14 tumors with relaxed GNAS imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed GNAS imprinting showed significantly lower SSTR2 and AIP expression levels. Conclusion: Altered A/B DMR methylation was found exclusively in gsp-negative somatotroph tumors. 43% of gsp-negative tumors showed GNAS imprinting relaxation, which correlated with lower GNAS, SSTR2 and AIP expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior.

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Monoallelic Expression of Pax5: A Paradigm for the Haploinsufficiency of Mammalian Pax Genes?

Biological Chemistry ◽

10.1515/bc.1999.077 ◽

1999 ◽

Vol 380 (6) ◽

Cited By ~ 31

Author(s):

S.L. Nutt ◽

M. Busslinger

Keyword(s):

Human Disease ◽

Mouse Genome ◽

Monoallelic Expression ◽

Wild Type Allele ◽

Loss Of Function ◽

Wild Type ◽

Type Allele ◽

Pax Genes ◽

Default State ◽

Mammalian Genes

AbstractIt is generally assumed that most mammalian genes are transcribed from both alleles. Hence, the diploid state of the genome offers the advantage that a loss-of-function mutation in one allele can be compensated for by the remaining wild-type allele of the same gene. Indeed, the vast majority of human disease syndromes and engineered mutations in the mouse genome are recessive, indicating that recessiveness is the ‘default’ state. However, a minority of genes are semi-dominant, as heterozygous loss-of-function mutation in these genes leads to phenotypic abnormalities. This condition, known as haploinsufficiency, has been described for five of the nine mammalian

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AFF3: a new player in maintaining XIST monoallelic expression

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjy082 ◽

2019 ◽

Vol 11 (9) ◽

pp. 723-724

Author(s):

Reiner A Veitia

Keyword(s):

Monoallelic Expression

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Assessing COVID-19 susceptibility through analysis of the genetic and epigenetic diversity of ACE2-mediated SARS-CoV-2 entry

Pharmacogenomics ◽

10.2217/pgs-2020-0092 ◽

2020 ◽

Vol 21 (18) ◽

pp. 1311-1329

Author(s):

Georgia Ragia ◽

Vangelis G Manolopoulos

Keyword(s):

At Risk ◽

Genetic Factors ◽

Genetic Data ◽

Disease Course ◽

Risk Population ◽

Epigenetic Diversity

There is considerable variation in disease course among individuals infected with SARS-CoV-2. Many of them do not exhibit any symptoms, while some others proceed to develop COVID-19; however, severity of COVID-19 symptoms greatly differs among individuals. Focusing on the early events related to SARS-CoV-2 entry to cells through the ACE2 pathway, we describe how variability in (epi)genetic factors can conceivably explain variability in disease course. We specifically focus on variations in ACE2, TMPRSS2 and FURIN genes, as central components for SARS-CoV-2 infection, and on other molecules that modulate their expression such as CALM, ADAM-17, AR and ESRs. We propose a genetic classifier for predicting SARS-CoV-2 infectivity potential as a preliminary tool for identifying the at-risk-population. This tool can serve as a dynamic scaffold being updated and adapted to validated (epi)genetic data. Overall, the proposed approach holds potential for better personalization of COVID-19 handling.

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An N-Ethyl-N-Nitrosourea Mutagenesis Screen for Epigenetic Mutations in the Mouse

Genetics ◽

10.1093/genetics/164.4.1481 ◽

2003 ◽

Vol 164 (4) ◽

pp. 1481-1494

Author(s):

Ivona Percec ◽

Joanne L Thorvaldsen ◽

Robert M Plenge ◽

Christopher J Krapp ◽

Joseph H Nadeau ◽

...

Keyword(s):

Genomic Imprinting ◽

X Chromosome ◽

X Inactivation ◽

Monoallelic Expression ◽

Chromosome 15 ◽

Chromosome 5 ◽

Chromosome 10 ◽

Mutagenesis Screen ◽

Distal Chromosome ◽

Males And Females

Abstract The mammalian epigenetic phenomena of X inactivation and genomic imprinting are incompletely understood. X inactivation equalizes X-linked expression between males and females by silencing genes on one X chromosome during female embryogenesis. Genomic imprinting functionally distinguishes the parental genomes, resulting in parent-specific monoallelic expression of particular genes. N-ethyl-N-nitrosourea (ENU) mutagenesis was used in the mouse to screen for mutations in novel factors involved in X inactivation. Previously, we reported mutant pedigrees identified through this screen that segregate aberrant X-inactivation phenotypes and we mapped the mutation in one pedigree to chromosome 15. We now have mapped two additional mutations to the distal chromosome 5 and the proximal chromosome 10 in a second pedigree and show that each of the mutations is sufficient to induce the mutant phenotype. We further show that the roles of these factors are specific to embryonic X inactivation as neither genomic imprinting of multiple genes nor imprinted X inactivation is perturbed. Finally, we used mice bearing selected X-linked alleles that regulate X chromosome choice to demonstrate that the phenotypes of all three mutations are consistent with models in which the mutations have affected molecules involved specifically in the choice or the initiation of X inactivation.

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