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Molecular Autism Jun 2024Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in...
BACKGROUND
Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.
METHODS
To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).
RESULTS
We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D on the order of 1 × 10).
LIMITATIONS
We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.
CONCLUSIONS
This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.
Topics: Humans; Autistic Disorder; Phenotype; Male; Female; Linkage Disequilibrium; Multifactorial Inheritance; Child; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Adult; Intellectual Disability
PubMed: 38877467
DOI: 10.1186/s13229-024-00605-5 -
MBio Jun 2024Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing...
Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing fungal meningitis worldwide, possesses five MAPKs. Among these, Cpk1, Hog1, and Mpk1 have established roles in sexual reproduction, stress responses, and cell wall integrity. However, the roles of Cpk2 and Mpk2 are less understood. Our study elucidates the functional interplay between the Cpk1/Cpk2 and Mpk1/Mpk2 MAPK pathways in . We discovered that overexpression compensates for Δ mating deficiencies via the Mat2 transcription factor, revealing functional redundancy between Cpk1 and Cpk2. We also found that Mpk2 is phosphorylated in response to cell wall stress, a process regulated by the MAPK kinase (MAP2K) Mkk2 and MAP2K kinases (MAP3Ks) Ssk2 and Ste11. Overexpression of partially restores cell wall integrity in Δ by influencing key cell wall components, such as chitin and the polysaccharide capsule. Contrarily, overexpression cannot restore thermotolerance and cell membrane integrity in Δ. These results suggest that Mpk1 and Mpk2 have redundant and opposing roles in the cellular response to cell wall and membrane stresses. Most notably, the dual deletion of and restores wild-type mating efficiency in Δ mutants via upregulation of the mating-regulating transcription factors and , suggesting that the Mpk1 and Mpk2 cooperate to negatively regulate the pheromone-responsive Cpk1 MAPK pathway. Our research collectively underscores a sophisticated regulatory network of cryptococcal MAPK signaling pathways that intricately govern sexual reproduction and cell wall integrity, thereby controlling fungal development and pathogenicity.IMPORTANCEIn the realm of fungal biology, our study on offers pivotal insights into the roles of specific proteins called mitogen-activated protein kinases (MAPKs). Here, we discovered the cryptic functions of Cpk2 and Mpk2, two MAPKs previously overshadowed by their dominant counterparts Cpk1 and Mpk1, respectively. Our findings reveal that these "underdog" proteins are not just backup players; they play crucial roles in vital processes like mating and cell wall maintenance in . Their ability to step in and compensate when their dominant counterparts are absent showcases the adaptability of . This newfound understanding not only enriches our knowledge of fungal MAPK mechanisms but also underscores the intricate balance and interplay of proteins in ensuring the organism's survival and adaptability.
PubMed: 38874410
DOI: 10.1128/mbio.01156-24 -
Frontiers in Microbiology 2024Ganoderic acids (GAs) are major functional components of . The study aimed to breed a new strain with increased contents of individual GAs. Two mating-compatible...
Ganoderic acids (GAs) are major functional components of . The study aimed to breed a new strain with increased contents of individual GAs. Two mating-compatible monokaryotic strains, G. 260125 and G. 260124, were successfully isolated from the dikaryotic CGMCC 5.0026 via protoplast formation and regeneration. The hemoglobin gene () and squalene synthase gene () were overexpressed in the monokaryotic G. 260124 and G. 260125 strain, respectively. Mating between the G. 260124 strain overexpressing and the G. 260125 strain overexpressing sqs resulted in the formation of the new hybrid dikaryotic strain sqs-vgb. The maximum contents of ganoderic acid (GA)-T, GA-Me, and GA-P in the fruiting body of the mated sqs-vgb strain were 23.1, 15.3, and 39.8 μg/g dry weight (DW), respectively, 2.23-, 1.75-, and 2.69-fold greater than those in 5.0026. The squalene and lanosterol contents increased 2.35- and 1.75-fold, respectively, in the fruiting body of the mated sqs-vgb strain compared with those in the 5.0026. In addition, the maximum expression levels of the and lanosterol synthase gene () were increased 3.23- and 2.13-fold, respectively, in the mated sqs-vgb strain. In summary, we developed a new strain with higher contents of individual GAs in the fruiting body by integrating genetic engineering and mono-mono crossing.
PubMed: 38873146
DOI: 10.3389/fmicb.2024.1410368 -
BioRxiv : the Preprint Server For... May 2024The datasets of large genotyping biobanks and direct-to-consumer genetic testing companies contain many related individuals. Until now, it has been widely accepted that...
The datasets of large genotyping biobanks and direct-to-consumer genetic testing companies contain many related individuals. Until now, it has been widely accepted that the most distant relationships that can be detected are around fifteen degrees (approximately 8 cousins) and that practical relationship estimates have a ceiling around ten degrees (approximately 5 cousins). However, we show that these assumptions are incorrect and that they are due to a misapplication of relationship estimators. In particular, relationship estimators are applied almost exclusively to putative relatives who have been identified because they share detectable tracts of DNA identically by descent (IBD). However, no existing relationship estimator conditions on the event that two individuals share at least one detectable segment of IBD anywhere in the genome. As a result, the relationship estimates obtained using existing estimators are dramatically biased for distant relationships, inferring all sufficiently distant relationships to be around ten degrees regardless of the depth of the true relationship. Moreover, existing relationship estimators are derived under a model that assumes that each pair of related individuals shares a single common ancestor (or mating pair of ancestors). This model breaks down for relationships beyond 10 generations in the past because individuals share many thousands of cryptic common ancestors due to pedigree collapse. We first derive a corrected likelihood that conditions on the event that at least one segment is observed between a pair of putative relatives and we demonstrate that the corrected likelihood largely eliminates the bias in estimates of pairwise relationships and provides a more accurate characterization of the uncertainty in these estimates. We then reformulate the relationship inference problem to account for the fact that individuals share many common ancestors, not just one. We demonstrate that the most distant relationship that can be inferred may be forty degrees or more, rather than ten, extending the time-to-common ancestor from approximately 200 years in the past to approximately 600 years in the past or more. This dramatic increase in the range of relationship estimators makes it possible to infer relationships whose common ancestors lived before historical events such as European settlement of the Americas and the Transatlantic Slave Trade, and possibly much earlier.
PubMed: 38868169
DOI: 10.1101/2024.05.13.594005 -
PloS One 2024The major histocompatibility complex (MHC) plays a key role in the adaptive immune system of vertebrates, and is known to influence mate choice in many species. In...
The major histocompatibility complex (MHC) plays a key role in the adaptive immune system of vertebrates, and is known to influence mate choice in many species. In birds, the MHC has been extensively examined but mainly in galliforms and passerines while other taxa that represent specific ecological and evolutionary life-histories, like seabirds, are underexamined. Here, we characterized diversity of MHC Class II B exon 2 in a colonial pelagic seabird, the Little Auk (or Dovekie Alle alle). We further examined whether MHC variation could be maintained through balancing selection and disassortative mating. We found high polymorphism at the genotyped MHC fragment, characterizing 99 distinct alleles across 140 individuals from three populations. The alleles frequencies exhibited a similar skewed distribution in both sexes, with the four most commonly occurring alleles representing approximately 35% of allelic variation. The results of a Bayesian site-by-site selection analysis suggest evidence of balancing selection and no direct evidence for MHC-dependent disassortative mating preferences in the Little Auk. The latter result might be attributed to the high overall polymorphism of the examined fragment, which itself may be maintained by the large population size of the species.
Topics: Animals; Female; Male; Alleles; Gene Frequency; Genetic Variation; Selection, Genetic; Polymorphism, Genetic; Mating Preference, Animal; Birds; Charadriiformes; Bayes Theorem; Phylogeny; Genes, MHC Class II
PubMed: 38865310
DOI: 10.1371/journal.pone.0304275 -
PloS One 2024Boolean networks provide an effective mechanism for describing interactions and dynamics of gene regulatory networks (GRNs). Deriving accurate Boolean descriptions of...
Boolean networks provide an effective mechanism for describing interactions and dynamics of gene regulatory networks (GRNs). Deriving accurate Boolean descriptions of GRNs is a challenging task. The number of experiments is usually much smaller than the number of genes. In addition, binarization leads to a loss of information and inconsistencies arise in binarized time-series data. The inference of Boolean networks from binarized time-series data alone often leads to complex and overfitted models. To obtain relevant Boolean models of gene regulatory networks, inference methods could incorporate data from multiple sources and prior knowledge in terms of general network structure and/or exact interactions. We propose the Boolean network inference method SAILoR (Structure-Aware Inference of Logic Rules). SAILoR incorporates time-series gene expression data in combination with provided reference networks to infer accurate Boolean models. SAILoR automatically extracts topological properties from reference networks. These can describe a more general structure of the GRN or can be more precise and describe specific interactions. SAILoR infers a Boolean network by learning from both continuous and binarized time-series data. It navigates between two main objectives, topological similarity to reference networks and correspondence with gene expression data. By incorporating the NSGA-II multi-objective genetic algorithm, SAILoR relies on the wisdom of crowds. Our results indicate that SAILoR can infer accurate and biologically relevant Boolean descriptions of GRNs from both a static and a dynamic perspective. We show that SAILoR improves the static accuracy of the inferred network compared to the network inference method dynGENIE3. Furthermore, we compared the performance of SAILoR with other Boolean network inference approaches including Best-Fit, REVEAL, MIBNI, GABNI, ATEN, and LogBTF. We have shown that by incorporating prior knowledge about the overall network structure, SAILoR can improve the structural correctness of the inferred Boolean networks while maintaining dynamic accuracy. To demonstrate the applicability of SAILoR, we inferred context-specific Boolean subnetworks of female Drosophila melanogaster before and after mating.
Topics: Gene Regulatory Networks; Algorithms; Animals; Drosophila melanogaster; Models, Genetic; Logic; Computational Biology
PubMed: 38861487
DOI: 10.1371/journal.pone.0304102 -
PeerJ 2024For many species, the relationship between space use and diet composition is complex, with individuals adopting varying space use strategies such as territoriality to...
For many species, the relationship between space use and diet composition is complex, with individuals adopting varying space use strategies such as territoriality to facilitate resource acquisition. Coyotes () exhibit two disparate types of space use; defending mutually exclusive territories (residents) or moving nomadically across landscapes (transients). Resident coyotes have increased access to familiar food resources, thus improved foraging opportunities to compensate for the energetic costs of defending territories. Conversely, transients do not defend territories and are able to redirect energetic costs of territorial defense towards extensive movements in search of mates and breeding opportunities. These differences in space use attributed to different behavioral strategies likely influence foraging and ultimately diet composition, but these relationships have not been well studied. We investigated diet composition of resident and transient coyotes in the southeastern United States by pairing individual space use patterns with analysis of stable carbon (δC) and nitrogen (δN) isotope values to assess diet. During 2016-2017, we monitored 41 coyotes (26 residents, 15 transients) with GPS radio-collars along the Savannah River area in the southeastern United States. We observed a canopy effect on δC values and little anthropogenic food in coyote diets, suggesting C enrichment is likely more influenced by reduced canopy cover than consumption of human foods. We also observed other land cover effects, such as agricultural cover and road density, on δN values as well as reduced space used by coyotes, suggesting that cover types and localized, resident-like space use can influence the degree of carnivory in coyotes. Finally, diets and niche space did not differ between resident and transient coyotes despite differences observed in the proportional contribution of potential food sources to their diets. Although our stable isotope mixing models detected differences between the diets of resident and transient coyotes, both relied mostly on mammalian prey (52.8%, SD = 15.9 for residents, 42.0%, SD = 15.6 for transients). Resident coyotes consumed more game birds (21.3%, SD = 11.6 13.7%, SD = 8.8) and less fruit (10.5%, SD = 6.9 21.3%, SD = 10.7) and insects (7.2%, SD = 4.7 14.3%, SD = 8.5) than did transients. Our findings indicate that coyote populations fall on a feeding continuum of omnivory to carnivory in which variability in feeding strategies is influenced by land cover characteristics and space use behaviors.
Topics: Coyotes; Animals; Nitrogen Isotopes; Carbon Isotopes; Carnivory; Diet; Territoriality; Southeastern United States; Feeding Behavior
PubMed: 38854793
DOI: 10.7717/peerj.17457 -
BioRxiv : the Preprint Server For... May 2024Much of our understanding of functional genomics derives from insights gained from large strain libraries including the yeast deletion collection, the GFP and TAP-tagged...
Much of our understanding of functional genomics derives from insights gained from large strain libraries including the yeast deletion collection, the GFP and TAP-tagged libraries, QTL mapping populations, among others [1-5]. A limitation of these libraries is that it is not easy to introduce reporters or make genetic perturbations to all strains in these collections. Tools such as Synthetic Genetic Arrays allow for the genetic manipulation of these libraries but are labor intensive and require specialized equipment for high throughput pinning [6]. Manipulating a diverse library without losing diversity remains challenging. Ultimately, this limitation stems from the inefficiency of transformation, which is the standard method for genetic manipulation in yeast. Here, we develop a method that uses cytoduction (mating without nuclear fusion) to transfer plasmids directionally from a "Donor" to a diverse pool of "Recipient" strains. Because cytoduction uses mating, it is a natural process and is orders-of-magnitude more efficient than transformation, enabling the introduction of plasmids into high-diversity libraries with minimal impact on the diversity of the population.
PubMed: 38853837
DOI: 10.1101/2024.05.24.595802 -
Turkish Journal of Obstetrics and... Jun 2024To evaluate the outcome of human umbilical cord stem cells (HUMSC) administration on collagen expression within the frontal vaginal wall of menopausal rats.
OBJECTIVE
To evaluate the outcome of human umbilical cord stem cells (HUMSC) administration on collagen expression within the frontal vaginal wall of menopausal rats.
MATERIALS AND METHODS
We conducted an experimental, randomized post-test-only controlled group design. The study samples were 40 healthy female Winstar rat with the age of 8-12 weeks that had been ovariectomized, had never mated, and weighed 18-22 grams. The umbilical cord was obtained from voluntary donors who did not have a history of hepatitis B, hepatitis C, HIV, cytomegalovirus infection, treponema pallidum infection, or a history of other infections transmitted through the blood, placental tract, and genitals. Data collection (frontal vaginal wall of the rat) was carried out in a controlled environment with the consideration that all conditions were maintained equally and could be controlled.
RESULTS
There were 36 samples. A total of 13 menopausal rats (72%) had strong collagen expression and 5 rats had weak-to-moderate collagen expression (28%). On the other hand, 18 menopausal rats (100%) that belonged to the control group had weak-moderate collagen expression, and no menopausal rats appeared to have strong expression (0%). The administration of collagen to the anterior vaginal wall of postmenopausal rats proved to be effective by increasing the strong collagen expression in the damaged anterior vagina of postmenopausal female rats (p<0.05).
CONCLUSION
Administration of HUMSC resulted in an increase in collagen levels in the anterior vaginal tissue of postmenopausal female rats. These results demonstrate significant therapeutic potential for the treatment of pelvic floor dysfunction.
PubMed: 38853483
DOI: 10.4274/tjod.galenos.2024.01613 -
Lipids in Health and Disease Jun 2024Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction...
BACKGROUND
Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed.
METHODS
High-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent's reproductive function was assessed by sperm parameters and their DNMT's mRNA expression levels were also examined. The offspring's metabolic function was assessed by physiological, biochemical and molecular parameters.
RESULTS
The HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet.
CONCLUSION
The findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.
Topics: Animals; Sirtuin 1; Diet, High-Fat; Obesity; Male; Rats, Wistar; Female; Caloric Restriction; Rats; DNA Methylation; AMP-Activated Protein Kinases; Signal Transduction; Pregnancy
PubMed: 38851752
DOI: 10.1186/s12944-024-02161-6