Paternal Inheritance Research Articles

Survey of Echinochloa weed species in rice fields using a chloroplast DNA marker and spikelet characteristics identifies accessions with possible paternal inheritance and heteroplasmy

Survey of Echinochloa weed species in rice fields using a chloroplast DNA marker and spikelet characteristics identifies accessions with possible paternal inheritance and heteroplasmy

Genetic characteristics of the diploid offsprings in potato Cooperation 88 induced by diploid donor IVP101

Diploid lines (2n = 2x = 24) derived from tetraploid potato cultivars have been utilized to hybridize with wild diploid potato species, yielding fertile offsprings. Utilizing the pollen of Solanum tuberosum Group Phureja, such as IVP101, IVP35 and IVP48, as an inducer for wide hybridization with tetraploid cultivars represents a common method for producing diploids. In this study, we created a distant hybridization induced population of tetraploid potato cultivar Cooperation 88 (C88) and IVP101, and screened all diploids using flow cytometry and ploidyNGS. We investigated the genetic composition of chloroplast and nuclear genomes in 43 diploid offsprings. We found that all diploid offsprings share the same chloroplast genomic sequence as C88 and no evidence of paternal chloroplast inheritance was found. Used SNP data to calculate the theoretical introgression index of IVP101 with diploid offsprings. The results showed that the inducer’s nuclear genome was involved in the nuclear genome of the diploid offsprings with purple stem trait, indicating that the inducer nuclear genome was not completely eliminated in the nuclear genome during distant hybridization. Furthermore, we conducted a comparative analysis of the chloroplast genomes of the Solanum genus. The results indicated that (1) the chloroplast genome sizes of the 14 Solanum species ranged from 154,289 bp to 155,614 bp, with a total number of genes ranging 128-141, and with ycf1 and rps19 pseudogenes appearing at the IRB/SSC and IRA/LSC boundaries, respectively; (2) eight divergent hotspots distributed in the LSC and SSC regions of the Solanum chloroplast genomes were identified; (3) positive selection was detected in the clpP, rbcL, rps15, and rps4 genes, likely contributing to the adaptation of Solanum species to different habitats. These results reveal the variation and evolutionary characteristics of chloroplast genomes in Solanum plants.

Support for Y-compensation of mother's curse affecting lifespan in Drosophila melanogaster.

Mother's curse refers to male-biased deleterious mutations that may accumulate on mitochondria due to its strict maternal inheritance. If these mutations persist, males should ideally compensate through mutations on Y-chromosomes given its strict paternal inheritance. Previous work addressed this hypothesis by comparing coevolved and non-coevolved Y-mitochondria pairs placed alongside completely foreign autosomal backgrounds, expecting males with coevolved pairs to exhibit greater fitness due to Y-compensation. To date, no evidence for Y-compensation has been found. That experimental design assumes Y-chromosomes compensate via direct interaction with mitochondria and/or coevolved autosomes are unimportant in its function or elucidation. If Y-chromosomes instead compensate by modifying autosomal targets (or its elucidation requires coevolved autosomes), then this design could fail to detect Y-compensation. Here we address if Y-chromosomes ameliorate mitochondrial mutations affecting male lifespan in Drosophila melanogaster. Using three disparate populations we compared lifespan among males with coevolved and non-coevolved Y-mitochondria pairs placed alongside autosomal backgrounds coevolved with mitochondria. We found coevolved pairs exhibited lower mortality risk relative to non-coevolved pairs. In contrast, no such pattern was observed when coevolved and non-coevolved pairs were placed alongside non-coevolved autosomes, as with previous studies. These data are consistent with Y-compensation and highlight the importance of autosomes in this capacity. However, we cannot fully exclude the possibility that Y-autosomal coevolution independent of mitochondrial mutations contributed to our results. Regardless, modern practices in medicine, conservation, and agriculture that introduce foreign Y-chromosomes into non-coevolved backgrounds should be used with caution, as they may disrupt Y-autosome coadaptation and/or inadvertently unbridle mother's curse.

Spinocerebellar Ataxia in Brazil: A Comprehensive Genotype - Phenotype Analysis.

Spinocerebellar ataxias (SCAs) are a diverse group of hereditary neurodegenerative disorders characterized by progressive degeneration of the cerebellum and other parts of the nervous system. In this study, we examined the genotype‒phenotype correlations in SCAs within the Brazilian population by leveraging a comprehensive dataset of 763 individuals from SARAH Network of Rehabilitation Hospitals. Using a retrospective, cross-sectional, observational, multicentric approach, we analysed medical records and conducted standardized molecular testing to explore epidemiological characteristics, clinical manifestations, and genetic profiles of SCAs in Brazil. Our findings revealed the predominance of SCA3, followed by SCA7 and SCA2, which aligns with global trends and reflects the specific genetic landscape of Brazil. A significant inverse relationship between the age of symptom onset and CAG repeat length in the mutated allele was observed across SCAs 2, 3, and 7. This study also highlights a trend towards paternal inheritance in SCA2 and details the distribution of CAG repeat expansions, which correlates larger expansions with earlier onset and specific symptomatology. This extensive analysis underscores the critical importance of genetic testing in the diagnosis and management of SCAs and enlightens the intricate genotype‒phenotype interplay within a genetically diverse population. Despite certain limitations, such as potential selection bias and the retrospective nature of the study, our research provides invaluable insights into the prevalence, genetic underpinnings, and clinical variability of SCAs in Brazil. We suggest a broader demographic scope and investigations into nonmotor symptoms in future studies to obtain a more comprehensive understanding of SCAs.

Liberties of the genome: insertions of mitochondrial DNA fragments into nuclear genome.

The transition of detached fragments of mitochondrial DNA into the nucleus and their integration into chromosomal DNA is a special kind of genetic variability that highlights the relation between the two genomes and their interaction in a eukaryotic cell. The human genome contains several hundreds of insertions of mtDNA fragments (NUMTS). This paper presents an overview of the current state of research in this area. To date, evidence has been obtained that the occurrence of new mtDNA insertions in the nuclear genome is a seldom but not exceptionally rare event. The integration of new mtDNA fragments into the nuclear genome occurs during double-strand DNA break repair through the non-homologous end joining mechanism. Along with evolutionarily stable "genetic fossils" that were integrated into the nuclear genome millions of years ago and are shared by many species, there are NUMTS that could be species-specific, polymorphic in a species, or "private". Partial copies of mitochondrial DNA in the human nuclear genome can interfere with mtDNA during experimental studies of the mitochondrial genome, such as genotyping, heteroplasmy assessment, mtDNA methylation analysis, and mtDNA copy number estimation. In some cases, the insertion of multiple copies of the complete mitochondrial genome sequence may mimic paternal inheritance of mtDNA. The functional significance of NUMTS is poorly understood. For instance, they may be a source of variability for expression and splicing modulation. The role of NUMTS as a cause of hereditary diseases is negligible, since only a few cases of diseases caused by NUMTS have been described so far. In addition, NUMTS can serve as markers for evolutionary genetic studies. Of particular interest is the meaning of NUMTS in eukaryotic genome evolution. The constant flow of functionally inactive DNA sequences from mitochondria into the nucleus and its significance could be studied in view of the modern concepts of evolutionary theory suggesting non-adaptive complexity and the key role of stochastic processes in the formation of genomic structure.

Ribonuclease Inhibitor 1 (RNH1) Regulates Sperm tsRNA Generation for Paternal Inheritance through Interacting with Angiogenin in the Caput Epididymis.

Environmental stressors can induce paternal epigenetic modifications that are a key determinant of the intergenerational inheritance of acquired phenotypes in mammals. Some of them can affect phenotypic expression through inducing changes in tRNA-derived small RNAs (tsRNAs), which modify paternal epigenetic regulation in sperm. However, it is unclear how these stressors can affect changes in the expression levels of tsRNAs and their related endonucleases in the male reproductive organs. We found that Ribonuclease inhibitor 1 (RNH1), an oxidation responder, interacts with ANG to regulate sperm tsRNA generation in the mouse caput epididymis. On the other hand, inflammation and oxidative stress induced by either lipopolysaccharide (LPS) or palmitate (PA) treatments weakened the RNH1-ANG interaction in the epididymal epithelial cells (EEC). Accordingly, ANG translocation increased from the nucleus to the cytoplasm, which led to ANG upregulation and increases in cytoplasmic tsRNA expression levels. In conclusion, as an antioxidant, RNH1 regulates tsRNA generation through targeting ANG in the mouse caput epididymis. Moreover, the tsRNA is an epigenetic factor in sperm that modulates paternal inheritance in offspring via the fertilization process.

Paternal Mitochondrial DNA Leakage in Natural Populations of Large-Scale Loach, Paramisgurnus dabryanus.

Animal mitochondrial DNA is usually considered to comply with strict maternal inheritance, and only one mitochondrial DNA haplotype exists in an individual. However, mitochondrial heteroplasmy, the occurrence of more than one mitochondrial haplotype, has recently been reported in some animals, such as mice, mussels, and birds. This study conducted extensive field surveys to obtain representative samples to investigate the existence of paternal inheritance of mitochondrial DNA (mtDNA) in natural fish populations. Evidence of paternal mitochondrial DNA leakage of P. dabryanus was discovered using high-throughput sequencing and bioinformatics methods. Two distinct mitochondrial haplotypes (16,569 bp for haplotype I and 16,646 bp for haplotype II) were observed, differing by 18.83% in nucleotide sequence. Phylogenetic analysis suggests divergence between these haplotypes and potential interspecific hybridization with M. anguillicaudatus, leading to paternal leakage. In natural populations of P. dabryanus along the Yangtze River, both haplotypes are present, with Type I being dominant (75% copy number). Expression analysis shows that Type I has higher expression levels of ND3 and ND6 genes compared to Type II, suggesting Type I's primary role. This discovery of a species with two mitochondrial types provides a model for studying paternal leakage heterogeneity and insights into mitochondrial genome evolution and inheritance.

Parental Influence on Intracerebral Hemorrhage Onset in Hereditary Dutch-Type Cerebral Amyloid Angiopathy.

Dutch-type cerebral amyloid angiopathy (D-CAA) is an autosomal dominant hereditary form of CAA causing intracerebral hemorrhage (ICH) and cognitive decline. The age of onset of ICH in D-CAA mutation carriers is strikingly variable and ranges from late thirties up to 70 years. We investigated the presence of genetic anticipation and assessed the influence of parental age at onset and sex on age of ICH onset in offspring. We included (potential) D-CAA mutation carriers from our prospective D-CAA family database. Participants were sent a questionnaire by mail and asked for the onset age of symptomatic ICH and the onset age of symptomatic ICH of their affected first-degree relative(s), their siblings and affected parent. We used a Cox regression model with the age of onset of the parent as the covariate and the sex of the offspring as the factor. Next, we replaced the sex of the offspring with a factor with four levels: mother/daughter, mother/son, father/daughter, and father/son. We used a random effect per household. A total of 66 respondents completed the questionnaire. Reported mean age of first symptomatic ICH was similar (both 52 years, p = 0.87) for D-CAA parents (n = 60) and their offspring (n = 100). Offspring with a mother with D-CAA seemed to have an earlier ICH onset (50 years, standard deviation [SD] ± 7) than offspring with a paternal inheritance (54 years, SD ± 6, p = 0.03). There was no association between onset of first ICH of the parent and offspring after adding sex of the offspring to the Cox regression model: hazard ratio 0.99, 95% CI: 0.94-1.03, p = 0.51. The interaction between parent's sex and child's sex was not significant (p = 0.70). The results with and without random effect were essentially identical. We found no indication for genetic anticipation in D-CAA in general, although maternal inheritance seemed to be associated with an earlier ICH onset.

Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome

BackgroundSleep disturbances are a prevalent and complex comorbidity in neurodevelopmental disorders (NDDs). Dup15q syndrome (duplications of 15q11.2-13.1) is a genetic disorder highly penetrant for NDDs such as autism and intellectual disability and it is frequently accompanied by significant disruptions in sleep patterns. The 15q critical region harbors genes crucial for brain development, notably UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We previously described an electrophysiological biomarker of the syndrome, marked by heightened beta oscillations (12-30 Hz) in individuals with Dup15q syndrome, akin to electroencephalogram (EEG) alterations induced by allosteric modulation of GABAARs. Those with Dup15q syndrome exhibited increased beta oscillations during the awake resting state and during sleep, and they showed profoundly abnormal NREM sleep. This study aims to assess the translational validity of these EEG signatures and to delve into their neurobiological underpinnings by quantifying sleep physiology in chromosome-engineered mice with maternal (matDp/ + mice) or paternal (patDp/ + mice) inheritance of the full 15q11.2-13.1-equivalent duplication, and mice with duplication of just the UBE3A gene (Ube3a overexpression mice; Ube3a OE mice) and comparing the sleep metrics with their respective wildtype (WT) littermate controls.MethodsWe collected 48-h EEG/EMG recordings from 35 (23 male, 12 female) 12–24-week-old matDp/ + , patDp/ + , Ube3a OE mice, and their WT littermate controls. We quantified baseline sleep, sleep fragmentation, spectral power dynamics during sleep states, and recovery following sleep deprivation. Within each group, distinctions between Dup15q mutant mice and WT littermate controls were evaluated using analysis of variance (ANOVA) and student’s t-test. The impact of genotype and time was discerned through repeated measures ANOVA, and significance was established at p < 0.05.ResultsOur study revealed that across brain states, matDp/ + mice mirrored the elevated beta oscillation phenotype observed in clinical EEGs from individuals with Dup15q syndrome. Time to sleep onset after light onset was significantly reduced in matDp/ + and Ube3a OE mice. However, NREM sleep between Dup15q mutant and WT littermate mice remained unaltered, suggesting a divergence from the clinical presentation in humans. Additionally, while increased beta oscillations persisted in matDp/ + mice after 6-h of sleep deprivation, recovery NREM sleep remained unaltered in all groups, thus suggesting that these mice exhibit resilience in the fundamental processes governing sleep-wake regulation.ConclusionsQuantification of mechanistic and translatable EEG biomarkers is essential for advancing our understanding of NDDs and their underlying pathophysiology. Our study of sleep physiology in the Dup15q mice underscores that the beta EEG biomarker has strong translational validity, thus opening the door for pre-clinical studies of putative drug targets, using the biomarker as a translational measure of drug-target engagement. The unaltered NREM sleep may be due to inherent differences in neurobiology between mice and humans. These nuanced distinctions highlight the complexity of sleep disruptions in Dup15q syndrome and emphasize the need for a comprehensive understanding that encompasses both shared and distinct features between murine models and clinical populations.

Paternal obesity induces changes in sperm chromatin accessibility and has a mild effect on offspring metabolic health

The increasing global burden of metabolic disorders including obesity and diabetes necessitates a comprehensive understanding of their etiology, which not only encompasses genetic and environmental factors but also parental influence. Recent evidence has unveiled paternal obesity as a contributing factor to offspring's metabolic health via sperm epigenetic modifications. In this study, we investigated the impact of a Western diet-induced obesity in C57BL/6 male mice on sperm chromatin accessibility and the subsequent metabolic health of their progeny. Utilizing Assay for Transposase-Accessible Chromatin with sequencing, we discovered 450 regions with differential accessibility in sperm from obese fathers, implicating key developmental and metabolic pathways. Contrary to expectations, these epigenetic alterations in sperm were not predictive of long-term metabolic disorders in offspring, who exhibited only mild transient metabolic changes early in life. Both male and female F1 progeny showed no enduring predisposition to obesity or diabetes. These results underscore the biological resilience of offspring to paternal epigenetic inheritance, suggesting a complex interplay between inherited epigenetic modifications and the offspring's own developmental compensatory mechanisms. This study calls for further research into the biological processes that confer this resilience, which could inform interventional strategies to combat the heritability of metabolic diseases.

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry.

Although dose-response analyses are a fundamental tool in developmental toxicology, few studies have examined the impacts of toxicant dose on the non-genetic paternal inheritance of offspring disease and dysgenesis. In this study, we used geometric morphometric analyses to examine the impacts of different levels of preconception paternal alcohol exposure on offspring craniofacial shape and symmetry in a mouse model. Procrustes ANOVA followed by canonical variant analysis of geometric facial relationships revealed that Low-, Medium-, and High-dose treatments each induced distinct changes in craniofacial shape and symmetry. Our analyses identified a dose threshold between 1.543 and 2.321g/kg/day. Below this threshold, preconception paternal alcohol exposure induced changes in facial shape, including a right shift in facial features. In contrast, above this threshold, paternal exposures caused shifts in both shape and center, disrupting facial symmetry. Consistent with previous clinical studies, changes in craniofacial shape predominantly mapped to regions in the lower portion of the face, including the mandible (lower jaw) and maxilla (upper jaw). Notably, high-dose exposures also impacted the positioning of the right eye. Our studies reveal that paternal alcohol use may be an unrecognized factor contributing to the incidence and severity of alcohol-related craniofacial defects, complicating diagnostics of fetal alcohol spectrum disorders.

Inheritance of Mitochondria in Pelargonium Section Ciconium (Sweet) Interspecific Crosses

We have studied the inheritance of mitochondria in Pelargonium section Ciconium using 36 interspecific crosses generated. We designed KASP markers targeting four mitochondrial loci, belonging to the mitomes of four main crossing parents, enabling tracking the transmission of each mitome in the crosses. These markers discriminate between an individual species versus the other section Ciconium species. We found that maternal inheritance of mitochondria is most frequent, with occasional occurrences of paternal inheritance, while biparental inheritance is rare. For a P. multibracteatum crossing series, we found ambiguous results. Our results confirm those of previous studies, namely, that paternal inheritance of mitochondria can occur in P. sect Ciconium but that the instance is rare and much less common than is the case for chloroplasts.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Whole Exome Sequencing Revealed Paternal Inheritance of Obesity-related Genetic Variants in a Family with an Exclusively Breastfed Infant.

Obesity is a serious health problem, that progressively affects individuals' lives with comorbidities involving heart disease, stroke, and diabetes mellitus. Since its prevalence increases particularly in children under age-of-five years, its genetic and environmental causes should be determined for prevention and control of the disease. This study aimed to detect underlying genetic risk factors in a family with an exclusively breastfed obese infant. A three-generation family was recruited to be evaluated for obesity. Detailed examinations along with body mass indexcalculations were performed on available family members. Whole exome sequencing was performed on 7-month-oldobese infant utilizing Illumina-NextSeq550. Bioinformatic analyses were performed on the Genomize SEQ platform with variant filtering at minor allele frequencies (MAF)<1% for all normal populations. Sanger sequencing was applied in variant confirmation and family segregation. Neuro-motor developmental features were normal and genetic syndromes were excluded from the index. Early-onset severe obesity (4.25SDS weight-for-height) was obvious in index case, where his father and grandmother were also obese (BMIs: 38.1kg/m2 and 31.3kg/m2, respectively). WES analysis revealed deleterious variants in SH2B1, PDE11A, ADCY3, and CAPN10 genes previously associated with obesity. All variants were evaluated as novel candidates for obesity except PDE11A and family segregation confirmed paternal inheritance. This study confirmed the paternal inheritance of all potentially deleterious obesity-related variants. The cumulative effect of individual variants might explain the obesity phenotype in this family. The infant is recommended to be under periodic follow-up due to increased risk for later childhood obesity.

Pre-conceptional paternal diet impacts on offspring testosterone homoeostasis via epigenetic modulation of cyp19a1/aromatase activity

Paternal eating habits, before and at conception, have a strong impact on offspring future metabolism. By sending specific epigenetic signals through spermatozoa, paternal nutrition influences developing embryos and increases offspring risk of developing dysmetabolism and cardiovascular diseases. Among the intergenerational consequences, paternal epigenetic messages affect embryo DNA methylation altering programmed gene expression. The identification of offspring genetic loci that are epigenetically altered by paternal stimuli is of pivotal interest for timely post-natal treatment of offspring metabolic defects. We here use a murine model to show that, cyp19a1/aromatase, a gene coding for the cytochrome converting testosterone into 17-β estradiol (both potent hormonal mediators of embryo development and metabolism), is an epigenetic transducer of paternal intergenerational inheritance. By affecting cyp19a1 methylation status and alternative splicing, paternal diet coordinates androgens’ metabolism in the progeny affecting it in a sexually dimorphic way and promoting hypoandrogenism, growth retardation and diabetes in male pups.

Paternal Inheritance of Mitochondrial DNA May Lead to Dioecy in Conifers

In angiosperms cytoplasmic DNA is typically passed on maternally through ovules. Genes in the mtDNA may cause male sterility. When male-sterile (female) cytotypes produce more seeds than cosexuals, they pass on more copies of their mtDNA and will co-occur with cosexuals with a neutral cytotype. Cytoplasmic gynodioecy is a well-known phenomenon in angiosperms, both in wild and crop plants. In some conifer families (e.g. Pinaceae) mitochondria are also maternally inherited. However in some other families (e.g. Taxaceae and Cupressaceae) mtDNA is paternally inherited through the pollen. With paternal mtDNA inheritance, male cytotypes that produce more pollen than cosexuals are expected to co-occur with cosexuals. This is uncharted territory. An ESS model shows that the presence of male cytotypes selects for more female allocation in the cosexual, i.e. for sexual specialisation. An allele that switches sex from male to female can then invade. This leads to rapid loss of the neutral cytotype of the cosexual, fixation of the male cytotype and dioecy with 50% males and 50% females. The models suggest that paternal inheritance of mtDNA facilitates the evolution dioecy. Consistent with this hypothesis the Pinaceae are 100% monoecious, while dioecy is common in the Taxaceae family and in the genus Juniperus (Cupressaceae). However, no reliable data are yet available on both mode of inheritance of mtDNA and gender variation of the same species. When cosexuals benefit from reproductive assurance (high selfing rate, low inbreeding depression, low fertilisation) they maintain themselves next to males and females. This predicted pattern with three sex types present in the same population is observed in conifers in nature.

Maternal androgen exposure induces intergenerational effects via paternal inheritance.

Polycystic ovary syndrome (PCOS) is a condition resulting from the interaction between environmental factors and hereditary components, profoundly affecting offspring development. Although the etiology of this disease remains unclear, aberrant in utero androgen exposure is considered one of the pivotal pathogenic factors. Herein, we demonstrate the intergenerational inheritance of PCOS-like phenotypes in F2 female offspring through F1 males caused by maternal testosterone exposure in F0 mice. We found impaired serum hormone expression and reproductive system development in prenatal testosterone-treated F1 male and F2 female mice (PTF1 and PTF2). In addition, downregulated N6-methyladenosine (m6A) methyltransferase and binding proteins induced mRNA hypomethylation in the PTF1 testis, including frizzled-6 (Fzd6). In the PTF2 ovary, decreased FZD6 protein expression inhibited the mammalian target of rapamycin (mTOR) signaling pathway and activated Forkhead box O3 (FoxO3) phosphorylation, which led to impaired follicular development. These data indicate that epigenetic modification of the mTOR signaling pathway could be involved in the intergenerational inheritance of maternal testosterone exposure-induced impairments in the PTF2 ovary through male PTF1 mice.

CNS involvement in myotonic dystrophy type 1: does sex play a role?

Myotonic dystrophy type 1 (DM1) is a hereditary neuromuscular disorder affecting the central nervous system (CNS). Although sex differences have been explored in other neuromuscular disorders, research on this topic in DM1 remains limited. The present study aims to analyze sex differences (both the patient's and disease-transmitting parent's sex) with a focus on CNS outcomes. Retrospective data from 146 non-congenital DM1 patients were analyzed, including clinical, molecular, neuropsychological, and neuroradiological data. Sex and inheritance pattern differences were analyzed using t-tests, and ANOVA analyses were conducted to address the interactions. Overall, no significant sex differences were observed except in certain cognitive domains. However, individuals with maternal inheritance showed larger CTG expansion size, lower estimated IQs, and poorer performance on visual memory, executive functions, and language domains than those with paternal inheritance. Notably, IQ performance was independently influenced by inheritance pattern and CTG expansion. This study is the first to delve into sex differences in DM1 with a focus on CNS outcomes. While the results revealed the absence of a sex-specific clinic-molecular profile, more substantial CNS differences were observed between patients with maternal and paternal inheritance patterns. The hypothetical existence of genomic imprinting and its potential mechanism are discussed. These findings hold potential implications for aiding clinical management by improving genetic counseling and predicting disease severity and prognosis.

Investigating the role of mitochondrial membrane potential in paternal inheritance of mitochondria

Abstract The process of oxidative phosphorylation (OXPHOS) in mitochondria depends on an electrochemical gradient known as the mitochondrial membrane potential (Δψm). Reflecting high functionality, elevated Δψm usually depicts healthy mitochondria and contributes to organelle selection. This study investigates whether mitochondrial properties linked with bioenergetics, such as Δψm, play a role in paternal inheritance of mitochondria. More specifically, the study looks at how sperm Δψm responds to egg chemoattractants in bivalves characterized by distinct mitochondrial inheritance patterns: strict maternal inheritance (SMI) and doubly uniparental inheritance (DUI), the latter displaying sex-specific transmission of paternal mitochondrial DNA. Sperm Δψm was examined in four bivalve species: the blue mussel (Mytilus edulis) and the Manila clam (Ruditapes philippinarum) (DUI), plus the hard clam (Mercenaria mercenaria) and the soft-shell clam (Mya arenaria) (SMI). In the absence of egg chemoattractants, sperm Δψm did not vary between the two groups. However, there was a trend of increase in Δψm following egg detection only in sperm bearing paternally derived mitochondria (DUI). This suggests, along with bioenergetic changes, that Δψm modulation might be a specific property of at least some DUI species, possibly implicated in their unique ability to transmit their mitochondria in a sex-specific fashion.

Accession-specific parent-of-origin dependent and independent genome dosage effects on salt tolerance in Arabidopsis thaliana.

Improving the salt stress tolerance of crops is an important goal in plant breeding. Changes in the number of chromosome sets (i.e. ploidy level) cause genome dosage effects which can result in enhanced or novel traits. Maternal inheritance versus paternal inheritance of the same chromosome sets can have differential epigenetic effects on traits of F1 offspring. Hence, genome dosage effects can be parent-of-origin independent or dependent. The model plant Arabidopsis thaliana displays both genome dosage and parent-of-origin effects on plant growth under non-stress conditions. Using an isogenic ploidy series of diploid, triploid and tetraploid lines, we investigate the extent of genome dosage effects and their parent-of-origin dependency on in vitro salt stress tolerance of seedlings across 10 different A. thaliana accessions (genetic backgrounds). We detected genome dosage effects on salt stress tolerance for tetraploid lines in five accessions. In addition, through the generation of isogenic reciprocal F1 triploid lines, both parent-of-origin dependent and independent genome dosage effects on salt stress tolerance were detected. Thus, our results indicate not only that genome dosage balance effects can have significant impacts on abiotic stress tolerance in A. thaliana but also that parent-of-origin specific genome dosage effects can affect salt stress tolerance in plants.