Parental Origin Research Articles

Genetic parameters of feeding behaviour traits in ducks bred for foie gras production

The mule duck accounts for over 90% of French foie gras production, a sector where feed represents two-thirds of production costs. This study focuses on analysing the feeding behaviours of the mule duck and its parental populations (Pekin and Muscovy) using automated feeders. To assess feed efficiency, feed conversion ratio and residual feed intake were analysed, along with six traits derived at the daily and meal levels. Genetic parameters were estimated separately in purebred populations, as well as with a joint crossbred model that estimated the parental contributions to the hybrid crossbred performances. In relation to higher feed intakes and much−reduced feeding times (P < 0.001), the feeding rate in the Pekin population was twice as high as in the Muscovy population (19 g/min vs 9 g/min), while the mule duck exhibited a large heterosis for this trait (29 g/min). Feeding traits exhibited moderate (0.38 ± 0.11) to high (0.65 ± 0.11) heritabilities. Similar correlation patterns were observed between feeding traits in the two parental populations. In the Pekin line, the feed conversion ratio did not significantly correlate with feeding traits except for daily feed intake. However, in the Muscovy population, it was negatively correlated with the number of meals (−0.51 ± 0.21) and positively with meal feed intake and meal duration (+0.79 ± 0.17 and + 0.71 ± 0.26, respectively). The contributions of the two parental species to the hybrid’s performance differed, with the Pekin contributing more to feeding and meat traits compared to the Muscovy. They were similar only for liver weight. Additionally, unfavourable correlations between meat traits and liver traits were estimated in both pathways. Genetic relationships between feeding traits and slaughter traits varied by parental origin, suggesting different strategies for improving hybrid performance in the two parental species. However, in both pathways, genetic correlations between feed conversion ratio and meat traits (breast muscle and thigh weights) were favourable (<−0.42 ± 0.18), whereas they were unfavourable (>0.41 ± 0.20) for fatty liver weight. Altogether, improving liver traits and feed efficiency in the hybrid through selection in the parental populations could be enhanced by considering feeding traits recorded with electronic feeders, provided that adverse correlations are properly accounted for in a multitrait index.

Negative parental and offspring environmental effects of macroalgae on coral recruitment are linked with alterations in the coral larval microbiome.

The persistence of reef-building corals is threatened by macroalgal competitors leading to a major demographic bottleneck in coral recruitment. Whether parental effects exist under coral-algal competition and whether they influence offspring performance via microbiome alterations represent major gaps in our understanding of the mechanisms by which macroalgae may hinder coral recovery. We investigated the diversity, variability and composition of the microbiome of adults and larvae of the coral Pocillopora acuta and surrounding benthic substrate on algal-removed and algal-dominated bommies. We then assessed the relative influence of parental and offspring environmental effects on coral recruitment processes by reciprocally exposing coral larvae from two parental origins (algal-removed and algal-dominated bommies) to algal-removed and algal-dominated environmental conditions. Dense macroalgal assemblages impacted the microbiome composition of coral larvae. Larvae produced by parents from algal-dominated bommies were depleted in putative beneficial bacteria and enriched in opportunistic taxa. These larvae had a significantly lower survival compared to larvae from algal-removed bommies regardless of environmental conditions. In contrast, algal-induced parental and offspring environmental effects interacted to reduce the survival of coral recruits. Together our results demonstrate negative algal-induced parental and offspring environmental effects on coral recruitment that could be mediated by alterations in the offspring microbiome.

Confirmation and pathogenicity of small copy number variations incidentally detected via a targeted next-generation sequencing–based preimplantation genetic testing for aneuploidy platform

ObjectiveTo evaluate the technical accuracy, inheritance, and pathogenicity of small copy number variants (CNVs) detected by a targeted next-generation sequencing (NGS)-based PGT-A platform. DesignRetrospective observational study performed between 2020-2022. Subjects12,157 patients who underwent clinical PGT-A performed by targeted NGS for whole chromosome and large segmental aneuploidies. ExposureAn incidental finding was reported when a CNV gain/loss of at least three consecutive amplicons appeared in at least two embryos from the same IVF cycle. Main Outcome MeasuresThe primary outcome measures were the specificity, incidence, inheritance, and pathogenicity of small CNVs detected by the PGT-A platform. Accuracy of the PGT-A platform CNV calls was assessed via concordance with the CNV calls (size and genomic location) on chromosomal microarray of the gamete provider(s). Parental origin of the CNV and pathogenicity classifications were also reported. ResultsIn 75 of 12,157 unique PGT-A patients (0.62%;95%CI:0.5-0.8%), an incidental finding that met reporting criteria was identified. Chromosomal microarray follow-up was requested for all cases and results were received for one or both members of 65 reproductive couples. In all cases, one of the gamete providers was confirmed to have the CNV identified in the embryos (100.0%: N=65/65 95%CI:94.5-100). The identified CNV was of maternal origin in 34 cases (52.3%) and of paternal origin in 31 cases (47.7%). A significant correlation was identified between PGT-A-predicted CNV sizes and chromosomal microarray detected sizes (r=0.81) and genomic coordinates on parental DNA. Twenty-six (40%) of the CNVs were classified as benign/likely benign, 30 (46.2%) as a variant of uncertain significance (VUS), and 9 (13.8%) as pathogenic/likely pathogenic. ConclusionCertain PGT-A platforms may enable the detection of inherited, small CNVs with extremely high specificity without prior knowledge of parental status. The majority of CNVs in this data set were confirmed to be benign/likely benign or a VUS; however, pathogenic/likely pathogenic CNVs associated with a broad range of phenotypic features may also be detected, although a reliable negative predictive value for small CNVs with current PGT-A technologies is unknown due to the many technical challenges.

Mapping of long interspersed element-1 (L1) insertions by TIPseq provides information about sub chromosomal genetic variation in human embryos.

Retrotransposons play important roles during early development when they are transiently de-repressed during epigenetic reprogramming. Long interspersed element-1 (L1), the only autonomous retrotransposon in humans, comprises 17% of the human genome. We applied the Single Cell Transposon Insertion Profiling by Sequencing (scTIPseq) to characterize and map L1 insertions in human embryos. Sixteen cryopreserved, genetically tested, human blastocysts, were accessed from consenting couples undergoing IVF at NYU Langone Fertility Center. Additionally, four trios (father, mother, and embryos) were also evaluated. scTIPseq was applied to map L1 insertions in all samples, using L1 locations reported in the 1000 Genomes as controls. Twenty-nine unknown and unique insertions were observed in the sixteen embryos. Most were intergenic; no insertions were located in exons or immediately upstream of genes. The location or number of unknown insertions did not differ between euploid and aneuploid embryos, suggesting they are not merely markers of aneuploidy. Rather, scTIPseq provides novel information about sub-chromosomal structural variation in human embryos. Trio analyses showed a parental origin of all L1 insertions in embryos. Several studies have measured L1 expression at different stages of development in mice, but this study for the first time reports unknown insertions in human embryos that were inherited from one parent, confirming no de novo L1 insertions occurred in parental germline or during embryogenesis. Since one-third of euploid embryo transfers fail, future studies would be useful for understanding whether these sub-chromosomal genetic variants or de novo L1 insertions affect embryo developmental potential.

Genetic analysis of two families with abnormal findings upon prenatal diagnosis

To carry out genetic analysis on two families with carriers of small terminal translocations using karyotyping analysis and genomic copy number variation sequencing (CNV-seq). Two couples undergoing prenatal diagnosis at the Tianjin Central Hospital of Obstetrics and Gynecology respectively on April 12, 2020 and December 17, 2021 were selected as the study subjects. With informed consent, amniotic fluid and peripheral blood samples were collected and subjected to conventional karyotyping and CNV-seq analysis for the detection of chromosomal microdeletion/duplications. Both couples had given births to children with chromosomal aberrations previously, and both fetuses were found to have abnormal karyotypes. CNV-seq showed that they had harbored microdeletion/duplications, and their mothers had both carried balanced translocations involving terminal fragments of chromosomes. For fetuses with small chromosomal segmental abnormalities, their parental origin should be traced, and the diagnosis should be confirmed with combined genetic techniques.

Ideal phenotypic characteristics and parental lines for hybrid rice breeding to cope with global dimming

The global food crisis has intensified with climate change, and hybrid rice (Oryza sativa L.) is expected to play a crucial role in ensuring world food security. This study analyzed the parental origins and variety characteristics of 930 hybrid rice varieties bred in Sichuan Province, a typical low-light region and one of the main production areas for hybrid rice, from 2002 to 2022. The results indicate that these varieties were hybridized using 329 direct female and 539 direct male parents. Notably, the female parent Peiai 64 and the male parents Yuehesimiao and Fenghuazhan demonstrated a higher probability of breeding rice varieties with high yield and good quality. An ideal panicle type should possess more grains, a lower 1000-grain weight, a higher seed setting percentage, and greater grain density. It is recommended to increase the utilization of excellent parents in Sichuan Province, such as parents with ideal panicle type to improve resistance to climate change, particularly global dimming.

Uniparental silencing of 5S rRNA genes in plant allopolyploids - insights from Cardamine (Brassicaceae).

While the phenomenon of uniparental silencing of 35S rDNA in interspecific hybrids and allopolyploids is well documented, there is a notable absence of information regarding whether such silencing extends to the 5S RNA component of ribosomes. To address this gap in knowledge, we analyzed the 5S and 35S rDNA expression in Cardamine (Brassicaceae) allopolyploids, namely C. × insueta (2n = 3x = 24, genome composition RRA), C. flexuosa (2n = 4x = 32, AAHH), and C. scutata (2n = 4x = 32, PPAA) which share a common diploid ancestor (AA). We employed high-throughput sequencing of transcriptomes and genomes and phylogenetic analyses of 5S rRNA variants. The genomic organization of rDNA was further scrutinized through clustering and fluorescence in situ hybridization. In the C. × insueta allotriploid, we observed uniparental dominant expression of 5S and 35S rDNA loci. In the C. flexuosa and C. scutata allotetraploids, the expression pattern differed, with the 35S rDNA being expressed from the A subgenome, whereas the 5S rDNA was expressed from the partner subgenome. Both C. flexuosa and C. scutata but not C. × insueta showed copy and locus number changes. We conclude that in stabilized allopolyploids, transcription of ribosomal RNA components occurs from different subgenomes. This phenomenon appears to result in the formation of chimeric ribosomes comprising rRNA molecules derived from distinct parental origins. We speculate that the interplay of epigenetic silencing and rDNA rearrangements introduces an additional layer of variation in multimolecule ribosomal complexes, potentially contributing to the evolutionary success of allopolyploids.

GENETIC INSIGHTS AND BREEDING IMPLICATIONS: ENHANCING COTTON YIELD AND QUALITY THROUGH BIPARENTAL SELECTION

This study was performed in Egypt's Sakha Agriculture Research Station during the seasons 2015–2018 to study the efficiency of biparental progenies derived from inter-population random mating in F2 generation in a cotton cross. Intercrossing is allowed in cotton breeding populations. Although the best lines may include harmful alleles, thus early segregating generation recombination and hybridization are required. The F2 generation of the cotton cross (Giza70 TNB1), which obtained from Agriculture Research Center, Egypt, consisted of five male and eight female plants, was used to test biparental progeny from random interpopulation mating. About 28 and 24 families in BIPS1 and BIPS2 had their original parents were examined. All genotypes were assessed for agricultural and fiber qualities. The mean of families (BIPs2) was higher than BIPs1 for all measured metrics except lint yield, percentage, and uniformity ratio. BIPS2 families had more genotypic coefficients of variation (GCV) for features than BIPS1. Intercrossing affected correlation coefficients of BIPS1 and BIPS2 genotypes. Seed cotton yield and lint index genotypic correlations became considerable. Seed cotton yield estimated by seed index and first fruiting node location were altered from negative to positive. Among them, No.5, No.7, No.8, No.18, and No.19 had large yields and early ripening, as shown by their components. The top five families chosen for fiber length had gain values of 3.373% to 8.961% and 5.919 to 7.781% for fiber strength. The No.18 family exhibited good seed cotton production and fiber length. Intermating and self-pollination (BIPS2) may utilize non-additive gene effects and accumulate trait-influencing alleles. Continuing to select and evaluate families based on their large-scale reproductive performance will enhance the likelihood of producing genotypes with desired features. In conclusion, this study underscores the utility of continued selection based on discerned genetic parameters, genotypic correlations, and observed gains in facilitating the ongoing improvement of cotton breeding programs. By providing valuable insights into the intricacies of genetic variability and trait associations, this research holds implications not only for the advancement of cotton breeding practices but also for the broader agricultural landscape on both national and global scales. Keywords: Biparental, selection efficiency, correlated response, hybridization, self-pollination

The structure of the TH/INS locus and the parental allele expressed are not conserved between mammals

Parent-of-origin-specific expression of imprinted genes is critical for successful mammalian growth and development. Insulin, coded by the INS gene, is an important growth factor expressed from the paternal allele in the yolk sac placenta of therian mammals. The tyrosine hydroxylase gene TH encodes an enzyme involved in dopamine synthesis. TH and INS are closely associated in most vertebrates, but the mouse orthologues, Th and Ins2, are separated by repeated DNA. In mice, Th is expressed from the maternal allele, but the parental origin of expression is not known for any other mammal so it is unclear whether the maternal expression observed in the mouse represents an evolutionary divergence or an ancestral condition. We compared the length of the DNA segment between TH and INS across species and show that separation of these genes occurred in the rodent lineage with an accumulation of repeated DNA. We found that the region containing TH and INS in the tammar wallaby produces at least five distinct RNA transcripts: TH, TH-INS1, TH-INS2, lncINS and INS. Using allele-specific expression analysis, we show that the TH/INS locus is expressed from the paternal allele in pre- and postnatal tammar wallaby tissues. Determining the imprinting pattern of TH/INS in other mammals might clarify if paternal expression is the ancestral condition which has been flipped to maternal expression in rodents by the accumulation of repeat sequences.

Twisting the theory on the origin of human umbilical cord coiling featuring monozygotic twins.

The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell-cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development.

Accurate parent-of-origin variant assignment for multiple hereditary cancer syndromes using proband-only blood sample analysis.

10516 Background: Predicting which side of the family a germline variant comes from is a critical gap in current clinical practice, vital for risk management, variant curation, and cascade genetic testing. Assignment of any autosomal variant to either parent with 99% accuracy is now possible with only a blood sample from the proband. Parent-of-Origin-Aware genomic analysis (POAga) is achieved by combining methylation and sequence data from Oxford Nanopore long-read sequencing with chromosome-length haplotypes generated from Strand-seq to infer parent of origin of any variant along the length of a chromosome, due to accurate phasing of imprinted differentially methylated regions that occur on each autosome. We sought to validate POAga in common, high penetrant hereditary cancer conditions such as hereditary breast and ovarian cancer (HBOC) and Lynch syndrome, rarer syndromes with parent-of-origin-effects and other genes predisposing to breast cancer and gastrointestinal malignancies that are associated with genes across multiple chromosomes. Methods: Blood samples from carriers of pathogenic variants in ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, PMS2, EPCAM, PALB2, SDHD and SDHAF2, with known parental segregation, are currently being ascertained to determine the analytic validity of POAga in real world samples of differing age, sex, ethnicity, and cancer status. Samples are undergoing whole genome analysis by long and short read sequencing. Parent-of-origin of the pathogenic or likely pathogenic variant or variant of uncertain significance is predicted according to previously described methods (Akbari V, Hanlon VCT, et al. Cell Genom. 2022 Dec 21;3(1):100233.) under an REB approved protocol. Results: To date, analysis is complete for 100 individuals with a total of 107 rare or pathogenic germline variants with known or presumed parental segregation. Germline variants are in SDHD (n = 18), BRCA2 (n = 17), BRCA1 (n = 14), MLH1 (n = 10), PALB2 (n = 9), PMS2 (n = 8), MSH2 (n = 9), MSH6 (n = 7), ATM (n = 5), CDH1 (n = 5), SDHAF2 (n = 1), DICER1 (n = 1), MUTYH (n = 1), RET (n = 1), and EPCAM (n = 1). Of variants able to be assigned a parent-of-origin (n = 104 of 107, 97%), there was complete concordance between the predicted parent-of-origin and known clinical segregation (n = 104, 100%). Conclusions: Results to date support the ability of POAga to accurately infer parent-of-origin of rare or pathogenic variants with known parental segregation using only a blood sample from carriers of diverse hereditary cancer syndromes. Ongoing validation of POAga will continue to test its feasibility in real-world samples and inform its path towards clinically translation. Parent-of-Origin-Aware genomic analysis is a powerful technology that could improve our understanding of hereditary cancer syndromes and transform our ability to conduct genetic cancer risk assessments for patients and families.

Childhood adversity trajectories and weight status in young adult men: a register-based study including 359,783 Danish men

BackgroundChildhood adversity has previously been associated with overweight and obesity in adult life, but there is a need for larger population-based studies using prospectively obtained adversity trajectories across childhood to confirm these associations. Moreover, childhood adversity may also be associated with underweight, which is less often studied. The aim of the current study is to investigate the association between childhood adversity trajectories from 0–15 years with weight categories in young adult men.MethodsThe Danish Life Course Cohort (DANLIFE) was linked with the Danish Conscription Registry resulting in a study sample of 359,783 men, who have been assigned to one of five previously identified adversity trajectories from 0–15 years: “low adversity”, “early material deprivation”, “persistent material deprivation”, “loss or threat of loss”, and “high adversity”. Height and weight in young adulthood was assessed at a draft board examination at age 18–26 years. Associations of adversity trajectories and weight categories were investigated in multinomial regression models.ResultsCompared with the “low adversity” group, the four other adversity groups had higher risks of underweight, overweight, and obesity. The “high adversity” group showed the strongest associations with both underweight (1.44 (1.32, 1.58)) and obesity (1.50 (1.39, 1.61)) when adjusted for parental origin, birth year, age at draft board examination, and maternal age.ConclusionChildhood adversity, experienced between 0 and 15 years of life, was associated with a higher risk of underweight, overweight, and obesity in young adulthood among men.

Early life exposure to vitamin D deficiency impairs molecular mechanisms that regulate liver cholesterol biosynthesis, energy metabolism, inflammation, and detoxification.

Emerging data suggests liver disease may be initiated during development when there is high genome plasticity and the molecular pathways supporting liver function are being developed. Here, we leveraged our Collaborative Cross mouse model of developmental vitamin D deficiency (DVD) to investigate the role of DVD in dysregulating the molecular mechanisms underlying liver disease. We defined the effects on the adult liver transcriptome and metabolome and examined the role of epigenetic dysregulation. Given that the parental origin of the genome (POG) influences response to DVD, we used our established POG model [POG1-(CC011xCC001)F1 and POG2-(CC001xCC011)F1] to identify interindividual differences. We found that DVD altered the adult liver transcriptome, primarily downregulating genes controlling liver development, response to injury/infection (detoxification & inflammation), cholesterol biosynthesis, and energy production. In concordance with these transcriptional changes, we found that DVD decreased liver cell membrane-associated lipids (including cholesterol) and pentose phosphate pathway metabolites. Each POG also exhibited distinct responses. POG1 exhibited almost 2X more differentially expressed genes (DEGs) with effects indicative of increased energy utilization. This included upregulation of lipid and amino acid metabolism genes and increased intermediate lipid and amino acid metabolites, increased energy cofactors, and decreased energy substrates. POG2 exhibited broader downregulation of cholesterol biosynthesis genes with a metabolomics profile indicative of decreased energy utilization. Although DVD primarily caused loss of liver DNA methylation for both POGs, only one epimutation was shared, and POG2 had 6.5X more differentially methylated genes. Differential methylation was detected at DEGs regulating developmental processes such as amino acid transport (POG1) and cell growth & differentiation (e.g., Wnt & cadherin signaling, POG2). These findings implicate a novel role for maternal vitamin D in programming essential offspring liver functions that are dysregulated in liver disease. Importantly, impairment of these processes was not rescued by vitamin D treatment at weaning, suggesting these effects require preventative measures. Substantial differences in POG response to DVD demonstrate that the parental genomic context of exposure determines offspring susceptibility.

Efficient inference of parent-of-origin effect using case-control mother–child genotype data

Parent-of-origin effect plays an important role in mammal development and disorder. Case-control mother–child pair genotype data can be used to detect parent-of-origin effect and is often convenient to collect in practice. Most existing methods for assessing parent-of-origin effect do not incorporate any covariates, which may be required to control for confounding factors. We propose to model the parent-of-origin effect through a logistic regression model, with predictors including maternal and child genotypes, parental origins, and covariates. The parental origins may not be fully inferred from genotypes of a target genetic marker, so we propose to use genotypes of markers tightly linked to the target marker to increase inference efficiency. A robust statistical inference procedure is developed based on a modified profile log-likelihood in a retrospective way. A computationally feasible expectation–maximization algorithm is devised to estimate all unknown parameters involved in the modified profile log-likelihood. This algorithm differs from the conventional expectation–maximization algorithm in the sense that it is based on a modified instead of the original profile log-likelihood function. The convergence of the algorithm is established under some mild regularity conditions. This expectation–maximization algorithm also allows convenient handling of missing child genotypes. Large sample properties, including weak consistency, asymptotic normality, and asymptotic efficiency, are established for the proposed estimator under some mild regularity conditions. Finite sample properties are evaluated through extensive simulation studies and the application to a real dataset.

Molecular genetic characterization analysis of a novel HIV-1 circulating recombinant form (CRF156_0755) in Guangdong, China.

The characteristic of human immunodeficiency virus type 1 (HIV-1) is its susceptibility to erroneous replication and recombination, which plays a crucial role in the diverse and dynamic variation of HIV-1. The spread of different subtypes in the same population often leads to the emergence of circulating recombination forms (CRFs). At present, the main recombinant subtypes of HIV-1 in China are CRF07_BC, CRF01_AE, CRF08_BC and B' subtypes, while CRF55_01B has become the fifth major epidemic strain in China after rapid growth in recent years since it was first reported in 2013. In this study, we obtained five nearly full-length genomes (NFLGs) and one half-length genome from five different cities in Guangdong. Here, we focused on analyzing their characteristics, parental origin and drug resistance. Plasma samples were collected from six HIV-1 infected patients in Guangdong Province who had no epidemiological association with each other. The NFLGs of HIV-1 were amplified in two overlapping segments by the near-terminal dilution method. The positive products were sequenced directly to obtain genomic sequences. The recombinant patterns and breakpoints of the NFLGs were determined using the Simplot software and confirmed by the maximum likelihood trees for segments using the IQ-TREE and BEAST software. The genotypic resistance profiles of the protease reverse transcriptase and integrase were resolved by the Stanford HIV drug resistance database. The six genomes shared highly similar recombinant pattern, with the CRF55_01B backbone substituted by CRF07_BC segments, therefore assigned as CRF156_0755. The evolutionary analysis of the segments showed that CRF07_BC segments were not clustered with the Chinese MSM variants in the CRF07_BC lineage. All the five NFLGs were identified with the non-nucleoside reverse-transcription inhibitors (NNRTIs) resistance mutation V179E. With the accumulation and evolution of recombination between CRF55_01B and CRF 07_BC, the prevalence of more recombinant strains of CRF55_01B and CRF 07_BC may occur. Therefore, it is necessary to strengthen the identification and monitoring of the recombination of CRF55_01B and CRF 07_BC.

22q11.2 Deletion Syndrome: Influence of Parental Origin on Clinical Heterogeneity.

22q11.2 deletion syndrome (22q11.2DS) shows significant clinical heterogeneity. This study aimed to explore the association between clinical heterogeneity in 22q11.2DS and the parental origin of the deletion. The parental origin of the deletion was determined for 61 individuals with 22q11.2DS by genotyping DNA microsatellite markers and single-nucleotide polymorphisms (SNPs). Among the 61 individuals, 29 (47.5%) had a maternal origin of the deletion, and 32 (52.5%) a paternal origin. Comparison of the frequency of the main clinical features between individuals with deletions of maternal or paternal origin showed no statistically significant difference. However, Truncus arteriosus, pulmonary atresia, seizures, and scoliosis were only found in patients with deletions of maternal origin. Also, a slight difference in the frequency of other clinical features between groups of maternal or paternal origin was noted, including congenital heart disease, endocrinological alterations, and genitourinary abnormalities, all of them more common in patients with deletions of maternal origin. Although parental origin of the deletion does not seem to contribute to the phenotypic variability of most clinical signs observed in 22q11.2DS, these findings suggest that patients with deletions of maternal origin could have a more severe phenotype. Further studies with larger samples focusing on these specific features could corroborate these findings.

Youth Discharged from Residential Mental Health Treatment: A Case Study of Four Youth Who Identify as Indigenous

Youth with complex mental health disorders who identify as Indigenous may access residential mental health treatment (RT). There is a dearth of reports focussed on their community adaptation following RT. The purpose for this report was to explore the experiences of youth who identify as Indigenous from their perspective and that of their caregivers in a provincial region in Canada. In the original case study, 25 youth and parents participated in interviews; four of these youth identified as Indigenous. Their experiences in the year following discharge from RT indicated improved family relationships, continued problems in peer relationships, and improvements in school engagement. Implications for practice such as the need for culturally sensitive community services are discussed.

The landscape of allelic expression and DNA methylation at the bovine SGCE/PEG10 locus.

Genomic imprinting is an epigenetic regulation in mammals in which a small subset of genes is monoallelically expressed dependent on their parental origin. A large imprinted domain, SGCE/PEG10 locus, is located on human chromosome 7q21s and mouse proximal chromosome 6. However, genomic imprinting of bovine SGCE/PEG10 cluster has not been systematically studied. In this study, we investigated allele expression of 14 genes of the SGCE/PEG10 locus in bovine somatic tissues and term placenta using a single nucleotide polymorphism (SNP)-based sequencing method. In addition to SGCE and PEG10, two conserved paternally expressed genes in human and mice, five other genes (TFPI2, GNG11, ASB4, PON1, and PON3) were paternally expressed. Three genes, BET1, COL1A2, and CASD1, exhibited tissue-specific monoallelic expression. CALCR showed monoallelic expression in tissues but biallelic expression in the placenta. Three genes, GNGT1, PPP1R9A, and PON2, showed biallelic expression in cattle. Five differentially methylated regions (DMRs) were found to be associated with the allelic expression of TFPI2, COL1A2, SGCE/PEG10, PON3, and ASB4 genes, respectively. The SGCE/PEG10 DMR is a maternally hypermethylated germline DMR, but TFPI2, COL1A2, PON3, and ASB4 DMRs are secondary DMRs. In summary, we identified five novel bovine imprinted genes (GNG11, BET1, COL1A2, CASD1, and PON1) and four secondary DMRs at the SGCE/PEG10 locus.

Expanding deep phenotypic spectrum associated with atypical pathogenic structural variations overlapping 15q11-q13 imprinting region.

The 15q11-q13 region is a genetic locus with genes subject to genomic imprinting, significantly influencing neurodevelopment. Genomic imprinting is an epigenetic phenomenon that causes differential gene expression based on the parent of origin. In most diploid organisms, gene expression typically involves an equal contribution from both maternal and paternal alleles, shaping the phenotype. Nevertheless, in mammals, including humans, mice, and marsupials, the functional equivalence of parental alleles is not universally maintained. Notably, during male and female gametogenesis, parental alleles may undergo differential marking or imprinting, thereby modifying gene expression without altering the underlying DNA sequence. Neurodevelopmental disorders, such as Prader-Willi syndrome (PWS) (resulting from the absence of paternally expressed genes in this region), Angelman syndrome (AS) (associated with the absence of the maternally expressed UBE3A gene), and 15q11-q13 duplication syndrome (resulting from the two common forms of duplications-either an extra isodicentric 15 chromosome or an interstitial 15 duplication), are the outcomes of genetic variations in this imprinting region. Conducted a genomic study to identify the frequency of pathogenic variants impacting the 15q11-q13 region in an ethnically homogenous population from Bangladesh. Screened all known disorders from the DECIPHER database and identified variant enrichment within this cohort. Using the Horizon analysis platform, performed enrichment analysis, requiring at least >60% overlap between a copy number variation and a disorder breakpoint. Deep clinical phenotyping was carried out through multiple examination sessions to evaluate a range of clinical symptoms. This study included eight individuals with clinically suspected PWS/AS, all previously confirmed through chromosomal microarray analysis, which revealed chromosomal breakpoints within the 15q11-q13 region. Among this cohort, six cases (75%) exhibited variable lengths of deletions, whereas two cases (25%) showed duplications. These included one type 2 duplication, one larger atypical duplication, one shorter type 2 deletion, one larger type 1 deletion, and four cases with atypical deletions. Furthermore, thorough clinical assessments led to the diagnosis of four PWS patients, two AS patients, and two individuals with 15q11-q13 duplication syndrome. Our deep phenotypic observations identified a spectrum of clinical features that overlap and are unique to PWS, AS, and Dup15q syndromes. Our findings establish genotype-phenotype correlation for patients impacted by variable structural variations within the 15q11-q13 region.

Provenance and the U–Pb age constraints on the tuff beds of the Late Jurassic–Early Cretaceous Bazhenovo Formation, West Siberian Basin

AbstractThin tuff beds of the Late Jurassic–Early Cretaceous Bazhenovo Formation are laterally widespread in the central part of the West Siberian Basin (ca 0.5 million km2). However, the source of the tuff beds remains unclear. The stratigraphy, geochemistry and geochronology of the tuff beds were investigated to reveal their magmatic origin and potential source region. Most of the tuff beds are recorded in member 4 and can be correlated through the Bazhenovo sequence. Thin‐section petrography and X‐ray diffraction indicate that the tuffs mostly comprise clay minerals and K‐feldspars. Less common minerals are plagioclase, quartz and pyrite. The geochemical composition of the Bazhenovo tuff beds suggests a parental magma origin of andesite/basalt, which came from volcanic arc‐related settings. Considering the results of geochemical studies along with LA‐ICP‐MS zircon U–Pb dating (141.3 ± 0.3/2.8 Ma), the palaeovolcanoes of the Caucasus region or south‐east Mongolia–North‐East China are one of the potential source regions of the tuffs. The record of these tuffs indicates the intensive volcanic eruption during the Volgian–Ryazanian, accompanied by a very low‐sedimentation rate and preservation in a reducing environment. The tuff beds have broad implications as an isochronous marker horizon and constraints for the numerical age of the Jurassic–Cretaceous boundary in the Boreal Realm.