Assembly of novel sequences for Chinese domestic pigs reveals new genes and regulatory variants providing new insights into their diversity.

There is an increasing understanding that a reference genome representing an individual cannot capture all the gene repertoire of a species. Here, we conduct a population-scale missing sequences detection of Chinese domestic pigs using whole-genome sequencing data from 534 individuals. We identify 132.41 Mb of sequences absent in the reference assembly, including eight novel genes. In particular, the breeds spread in Chinese high-altitude regions perform significantly different frequencies of new sequences in promoters than other breeds. Furthermore, we dissect the role of non-coding variants and identify a novel sequence inserted in the 3'UTR of the FMO3 gene, which may be associated with the intramuscular fat phenotype. This novel sequence could be a candidate marker for meat quality. Our study provides a comprehensive overview of the missing sequences in Chinese domestic pigs and indicates that this dataset is a valuable resource for understanding the diversity and biology of pigs.

Intergenic Regions of Saccharomycotina Yeasts are Enriched in Potential to Encode Transmembrane Domains.

Intergenic genomic regions have essential regulatory and structural roles that impose constraints on their sequences. But regions that do not currently encode proteins also carry the potential to do so in the future. De novo gene emergence, the evolution of novel genes out of previously noncoding sequences has now been established as a potent force for genomic novelty. Recently, it was shown that intergenic regions in the genome of Saccharomyces cerevisiae harbor pervasive cryptic potential to, if theoretically translated, form transmembrane domains (TM domains) more frequently than expected by chance given their nucleotide composition, a property that we refer to as TM-forming enrichment. The source and biological relevance of this property is unknown. Here, we expand the investigation into the TM-forming potential of intergenic regions to the entire Saccharomycotina budding yeast subphylum, in an effort to explain this property and understand its importance. We find pervasive but variable enrichment in TM-forming potential across the subphylum regardless of the composition and average size of intergenic regions. This cryptic property is evenly spread across the genome, cannot be explained by the hydrophobic content of the sequence, and does not appear to localize to regions containing regulatory motifs. This TM-forming enrichment specifically, and not the actual TM-forming potential, is associated, across genomes, with more TM domains in evolutionarily young genes. Our findings shed light on this newly discovered feature of yeast genomes and constitute a first step toward understanding its evolutionary importance.

Integrated full-length transcriptome and metabolome analysis reveals the defence response of melon to gummy stem blight.

Gummy stem blight (GSB), a widespread disease causing great loss to cucurbit production, has become a major threat to melon cultivation. However, the melon-GSB interaction remains largely unknown. Here, full-length transcriptome and widely targeted metabolome were used to investigate the defence responses of resistant (PI511089) and susceptible (Payzawat) melon accessions to GSB pathogen infection at 24 h. The biosynthesis of secondary metabolites and MAPK signalling pathway were specifically enriched for differentially expressed genes in PI511890, while carbohydrate metabolism and amino acid metabolism were specifically enriched in Payzawat. More than 1000 novel genes were identified and MAPK signalling pathway was specifically enriched for them in PI511890. There were 11 793 alternative splicing events involving in the defence response to GSB. Totally, 910 metabolites were identified in Payzawat and PI511890, and flavonoids were the dominant metabolites. Integrated full-length transcriptome and metabolome analysis showed eriodictyol and oxalic acid were the potential marker metabolites for GSB resistance in melon. Moreover, posttranscription regulation was widely involved in the defence response of melon to GSB pathogen infection. These results not only improve our understanding on the interaction between melon and GSB, but also facilitate the genetic improvement of melon with GSB resistance.

Genomic variation of 363 diverse tea accessions unveils the genetic diversity, domestication, and structural variations associated with tea adaptation.

Domestication has shaped the population structure and agronomic traits of tea plants, yet the complexity of tea population structure and genetic variation that determines these traits remains unclear. We here investigated the resequencing data of 363 diverse tea accessions collected extensively from almost all tea distributions and found that the population structure of tea plants was divided into eight subgroups, which were basically consistent with their geographical distributions. The genetic diversity of tea plants in China decreased from southwest to east as latitude increased. Results also indicated that Camellia sinensis var. assamica (CSA) illustrated divergent selection signatures with Camellia sinensis var. sinensis (CSS). The domesticated genes of CSA were mainly involved in leaf development, flavonoid and alkaloid biosynthesis, while the domesticated genes in CSS mainly participated in amino acid metabolism, aroma compounds biosynthesis, and cold stress. Comparative population genomics further identified ~730 Mb novel sequences, generating 6,058 full-length protein-encoding genes, significantly expanding the gene pool of tea plants. We also discovered 217,376 large-scale structural variations and 56,583 presence and absence variations (PAVs) across diverse tea accessions, some of which were associated with tea quality and stress resistance. Functional experiments demonstrated that two PAV genes (CSS0049975 and CSS0006599) were likely to drive trait diversification in cold tolerance between CSA and CSS tea plants. The overall findings not only revealed the genetic diversity and domestication of tea plants, but also underscored the vital role of structural variations in the diversification of tea plant traits.

Estimating transcriptome complexities across eukaryotes.

BACKGROUND: Genomic complexity is a growing field of evolution, with case studies for comparative evolutionary analyses in model and emerging non-model systems. Understanding complexity and the functional components of the genome is an untapped wealth of knowledge ripe for exploration. With the "remarkable lack of correspondence" between genome size and complexity, there needs to be a way to quantify complexity across organisms. In this study, we use a set of complexity metrics that allow for evaluating changes in complexity using TranD. RESULTS: We ascertain if complexity is increasing or decreasing across transcriptomes and at what structural level, as complexity varies. In this study, we define three metrics - TpG, EpT, and EpG- to quantify the transcriptome's complexity that encapsulates the dynamics of alternative splicing. Here we compare complexity metrics across 1) whole genome annotations, 2) a filtered subset of orthologs, and 3) novel genes to elucidate the impacts of orthologs and novel genes in transcript model analysis. Effective Exon Number (EEN) issued to compare the distribution of exon sizes within transcripts against random expectations of uniform exon placement. EEN accounts for differences in exon size, which is important because novel gene differences in complexity for orthologs and whole-transcriptome analyses are biased towards low-complexity genes with few exons and few alternative transcripts. CONCLUSIONS: With our metric analyses, we are able to quantify changes in complexity across diverse lineages with greater precision and accuracy than previous cross-species comparisons under ortholog conditioning. These analyses represent a step toward whole-transcriptome analysis in the emerging field of non-model evolutionary genomics, with key insights for evolutionary inference of complexity changes on deep timescales across the tree of life. We suggest a means to quantify biases generated in ortholog calling and correct complexity analysis for lineage-specific effects. With these metrics, we directly assay the quantitative properties of newly formed lineage-specific genes as they lower complexity.

PacBio single-molecule long-read sequencing provides new insights into the complexity of full-length transcripts in oriental river prawn, macrobrachium nipponense.

BACKGROUND: Oriental river prawn (Macrobrachium nipponense) is one of the most dominant species in shrimp farming in China, which is a rich source of protein and contributes to a significant impact on the quality of human life. Thus, more complete and accurate annotation of gene models are important for the breeding research of oriental river prawn. RESULTS: A full-length transcriptome of oriental river prawn muscle was obtained using the PacBio Sequel platform. Then, 37.99 Gb of subreads were sequenced, including 584,498 circular consensus sequences, among which 512,216 were full length non-chimeric sequences. After Illumina-based correction of long PacBio reads, 6,599 error-corrected isoforms were identified. Transcriptome structural analysis revealed 2,263 and 2,555 alternative splicing (AS) events and alternative polyadenylation (APA) sites, respectively. In total, 620 novel genes (NGs), 197 putative transcription factors (TFs), and 291 novel long non-coding RNAs (lncRNAs) were identified. CONCLUSIONS: In summary, this study offers novel insights into the transcriptome complexity and diversity of this prawn species, and provides valuable information for understanding the genomic structure and improving the draft genome annotation of oriental river prawn.

Highly sex specific gene expression in Jojoba.

BACKGROUND: Dioecious plants have male and female flowers on separate plants. Jojoba is a dioecious plant that is drought-tolerant and native to arid areas. The genome sequence of male and female plants was recently reported and revealed an X and Y chromosome system, with two large male-specific insertions in the Y chromosome. RESULTS: A total of 16,923 differentially expressed genes (DEG) were identified between the flowers of the male and female jojoba plants. This represented 40% of the annotated genes in the genome. Many genes, including those responsible for plant environmental responses and those encoding transcription factors (TFs), were specific to male or female reproductive organs. Genes involved in plant hormone metabolism were also found to be associated with flower and pollen development. A total of 8938 up-regulated and 7985 down-regulated genes were identified in comparison between male and female flowers, including many novel genes specific to the jojoba plant. The most differentially expressed genes were associated with reproductive organ development. The highest number of DEG were linked with the Y chromosome in male plants. The male specific parts of the Y chromosome encoded 12 very highly expressed genes including 9 novel genes and 3 known genes associated with TFs and a plant hormone which may play an important role in flower development. CONCLUSION: Many genes, largely with unknown functions, may explain the sexual dimorphisms in jojoba plants and the differentiation of male and female flowers.

Carcino-Evo-Devo, A Theory of the Evolutionary Role of Hereditary Tumors.

A theory of the evolutionary role of hereditary tumors, or the carcino-evo-devo theory, is being developed. The main hypothesis of the theory, the hypothesis of evolution by tumor neofunctionalization, posits that hereditary tumors provided additional cell masses during the evolution of multicellular organisms for the expression of evolutionarily novel genes. The carcino-evo-devo theory has formulated several nontrivial predictions that have been confirmed in the laboratory of the author. It also suggests several nontrivial explanations of biological phenomena previously unexplained by the existing theories or incompletely understood. By considering three major types of biological development-individual, evolutionary, and neoplastic development-within one theoretical framework, the carcino-evo-devo theory has the potential to become a unifying biological theory.

The early embryonic transcriptome of a Hawaiian Drosophila picture-wing fly shows evidence of altered gene expression and novel gene evolution.

A massive adaptive radiation on the Hawaiian archipelago has produced approximately one-quarter of the fly species in the family Drosophilidae. The Hawaiian Drosophila clade has long been recognized as a model system for the study of both the ecology of island endemics and the evolution of developmental mechanisms, but relatively few genomic and transcriptomic datasets are available for this group. We present here a differential expression analysis of the transcriptional profiles of two highly conserved embryonic stages in the Hawaiian picture-wing fly Drosophila grimshawi. When we compared our results to previously published datasets across the family Drosophilidae, we identified cases of both gains and losses of gene representation in D. grimshawi, including an apparent delay in Hox gene activation. We also found a high expression of unannotated genes. Most transcripts of unannotated genes with open reading frames do not have identified homologs in non-Hawaiian Drosophila species, although the vast majority have sequence matches in genomes of other Hawaiian picture-wing flies. Some of these unannotated genes may have arisen from noncoding sequence in the ancestor of Hawaiian flies or during the evolution of the clade. Our results suggest that both the modified use of ancestral genes and the evolution of new ones may occur in rapid radiations.

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative.

CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.

Novel Virulence Factors Deciphering Klebsiella pneumoniae KpC4 Infect Maize as a Crossing-Kingdom Pathogen: An Emerging Environmental Threat.

Klebsiella pneumoniae is not only a human and animal opportunistic pathogen, but a food-borne pathogen. Cross-kingdom infection has been focused on since K. pneumoniae was identified as the pathogen of maize, banana, and pomegranate. Although the pathogenicity of K. pneumoniae strains (from ditch water, maize, and human) on plant and mice has been confirmed, there are no reports to explain the molecular mechanisms of the pathogen. This study uncovered the K. pneumoniae KpC4 isolated from maize top rot for the determination of various virulence genes and resistance genes. At least thirteen plant disease-causing genes are found to be involved in the disruption of plant defense. Among them, rcsB is responsible for causing disease in both plants and animals. The novel sequence types provide solid evidence that the pathogen invades plant and has robust ecological adaptability. It is imperative to perform further studies on the verification of these KpC4 genes' functions to understand the molecular mechanisms involved in plant−pathogen interactions.

Identification of novel genes in testicular cancer microenvironment based on ESTIMATE algorithm-derived immune scores.

Testicular cancer is the most common solid malignancy among young men. We downloaded data of testicular cancer patients from The Cancer Genome Atlas database to find novel genes in the testicular cancer microenviroment based on ESTIMATE algorithm-derived immune scores. A total of 156 cases of testicular cancer were included in this study and 165 cases of normal testicular tissues were used. We divided the testicular cancer patients into high- and low-score groups based on their immune scores. We identified 1,226 differentially expressed genes (fold change > 2, false discovery rate < 0.05), including 688 downregulated genes and 538 upregulated genes, between these two groups. The top Gene Ontology terms were involved in the immune response-regulating cell surface receptor signaling pathway, immune response-activating cell surface receptor signaling pathway, external side of the plasma membrane, and receptor ligand activity. By performing the Kyoto Encyclopedia of Genes and Genomes analysis, we demonstrated that cAMP signaling pathway was highly enriched among these differentially expressed genes. High expression of LINC01564, LINC02208, ODAM, RNA5SP111, and RNU6-196P were found to be associated with poor overall survival. The expression of genes was further validated by the Human Protein Atlas and only ALB and IFNG were demonstrated to be differentially expressed between testis tissue and testicular cancer tissue.

A comprehensive RNA-Seq-based gene expression atlas of the summer squash (Cucurbita pepo) provides insights into fruit morphology and ripening mechanisms.

BACKGROUND: Summer squash (Cucurbita pepo: Cucurbitaceae) are a popular horticultural crop for which there is insufficient genomic and transcriptomic information. Gene expression atlases are crucial for the identification of genes expressed in different tissues at various plant developmental stages. Here, we present the first comprehensive gene expression atlas for a summer squash cultivar, including transcripts obtained from seeds, shoots, leaf stem, young and developed leaves, male and female flowers, fruits of seven developmental stages, as well as primary and lateral roots. RESULTS: In total, 27,868 genes and 2352 novel transcripts were annotated from these 16 tissues, with over 18,000 genes common to all tissue groups. Of these, 3812 were identified as housekeeping genes, half of which assigned to known gene ontologies. Flowers, seeds, and young fruits had the largest number of specific genes, whilst intermediate-age fruits the fewest. There also were genes that were differentially expressed in the various tissues, the male flower being the tissue with the most differentially expressed genes in pair-wise comparisons with the remaining tissues, and the leaf stem the least. The largest expression change during fruit development was early on, from female flower to fruit two days after pollination. A weighted correlation network analysis performed on the global gene expression dataset assigned 25,413 genes to 24 coexpression groups, and some of these groups exhibited strong tissue specificity. CONCLUSIONS: These findings enrich our understanding about the transcriptomic events associated with summer squash development and ripening. This comprehensive gene expression atlas is expected not only to provide a global view of gene expression patterns in all major tissues in C. pepo but to also serve as a valuable resource for functional genomics and gene discovery in Cucurbitaceae.

Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders.

STUDY QUESTION: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders? SUMMARY ANSWER: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%). WHAT IS KNOWN ALREADY: Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes. STUDY DESIGN, SIZE, DURATION: We performed exome sequencing in 21 patients with severe sperm motility disorders from two different clinics. PARTICIPANTS/MATERIALS, SETTING, METHOD: Two groups of infertile men, one from Argentina (n = 9) and one from Australia (n = 12), with clinically defined severe sperm motility disorders (motility <5%) and normal morphology values of 0-4%, were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on light and transmission electron microscopy. Sperm ultrastructural information was not available for the Australian cohort. Exome sequencing was performed in all 21 patients and variants with an allele frequency of <1% in the gnomAD population were prioritised and interpreted. MAIN RESULTS AND ROLE OF CHANCE: In 10 of 21 patients (48%), we identified pathogenic variants in known sperm assembly genes: CFAP43 (3 patients); CFAP44 (2 patients), CFAP58 (1 patient), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (55% and 42%, respectively). Furthermore, we identified patients with variants in the novel human candidate sperm motility genes: DNAH12, DRC1, MDC1, PACRG, SSPL2C and TPTE2. One patient presented with variants in four candidate genes and it remains unclear which variants were responsible for the severe sperm motility defect in this patient. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, we described patients with either a homozygous or two heterozygous candidate pathogenic variants in genes linked to sperm motility disorders. Due to unavailability of parental DNA, we have not assessed the frequency of de novo or maternally inherited dominant variants and could not determine the parental origin of the mutations to establish in all cases that the mutations are present on both alleles. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirm the likely causal role of variants in six known genes for sperm motility and we demonstrate that exome sequencing is an effective method to diagnose patients with severe sperm motility disorders (10/21 diagnosed; 48%). Furthermore, our analysis revealed six novel candidate genes for severe sperm motility disorders. Genome-wide sequencing of additional patient cohorts and re-analysis of exome data of currently unsolved cases may reveal additional variants in these novel candidate genes. STUDY FUNDING/COMPETING INTEREST(S): This project was supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., J.A.V. and R.I.M.L., The Netherlands Organisation for Scientific Research (918-15-667) to J.A.V., the Royal Society and Wolfson Foundation (WM160091) to J.A.V., as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. and Grants from the National Research Council of Argentina (PIP 0900 and 4584) and ANPCyT (PICT 9591) to H.E.C. and a UUKi Rutherford Fund Fellowship awarded to B.J.H.

Insights into regeneration tool box: An animal model approach.

For ages, regeneration has intrigued countless biologists, clinicians, and biomedical engineers. In recent years, significant progress made in identification and characterization of a regeneration tool kit has helped the scientific community to understand the mechanism(s) involved in regeneration across animal kingdom. These mechanistic insights revealed that evolutionarily conserved pathways like Wnt, Notch, Hedgehog, BMP, and JAK/STAT are involved in regeneration. Furthermore, advancement in high throughput screening approaches like transcriptomic analysis followed by proteomic validations have discovered many novel genes, and regeneration specific enhancers that are specific to highly regenerative species like Hydra, Planaria, Newts, and Zebrafish. Since genetic machinery is highly conserved across the animal kingdom, it is possible to engineer these genes and regeneration specific enhancers in species with limited regeneration properties like Drosophila, and mammals. Since these models are highly versatile and genetically tractable, cross-species comparative studies can generate mechanistic insights in regeneration for animals with long gestation periods e.g. Newts. In addition, it will allow extrapolation of regenerative capabilities from highly regenerative species to animals with low regeneration potential, e.g. mammals. In future, these studies, along with advancement in tissue engineering applications, can have strong implications in the field of regenerative medicine and stem cell biology.

Full length transcriptome profiling reveals novel immune-related genes in black rockfish (Sebastes schlegelii).

Lacking full-length transcriptome for black rockfish (Sebastes schlegelii) limits novel gene discoveries and gene structures analysis. Therefore, we constructed the full-length transcriptome of black rockfish using Single-Molecule Real-Time Sequencing technology. Totally, we produced 21.73 Gb raw reads containing 298,904 circular consensus sequence (CCS) reads. Full-length (FL) and Non-full-length (NFL) isoforms were obtained based on the presence of 5' and 3' primers as well as poly (A) tails. The results showed 70.71% reads were identified as FL isoforms. Moreover, the average length of these PacBio isoforms is 2,632 bp, which is much longer than the length of the unigenes with the average length of 589 bp which generated from Illumina platform. Meanwhile, we identified 43,068 non-redundant transcripts, 12,485 alternative splicing (AS), 6,320 polyadenylation (APA) and 499 gene fusions as well as numerous long non-coding RNAs based on mapped FL isoforms. In addition, we identified 147 and 528 immune-related genes from novel genes and unmapped transcripts. The provided dataset can be utilized to discover novel genes and construct a comprehensive transcript dataset for black rockfish.

Molecular diagnosis of epileptic encephalopathy of the first year of life applying a customized gene panel in a group of Argentinean patients.

OBJECTIVE: The aim of this study was to perform a molecular characterization of 17 Argentinean pediatric patients with diagnosis of having epileptic encephalopathies (EEs) of the first year of life without known etiology, applying next-generation sequencing (NGS). METHODS: We included 17 patients with EE with age of onset under 12 months without known etiology after ruling out structural abnormalities, metabolic disorders, and large chromosomal abnormalities. They presented with the following clinical phenotypes: Dravet syndrome (DS; n: 7), epilepsy of infancy with migrating focal seizures (EIMFS; n: 3), West syndrome (WS; n: 2), and undetermined epileptic encephalopathy (UEE; n: 5). Neurologic examinations, seizure semiology, brain magnetic resonance imaging, and standard electroencephalography (EEG) or video-EEG studies were performed in all cases. Using a custom amplicon strategy, we designed an NGS panel to study 47 genes associated with EEs. RESULTS: Pathogenic variants were detected in 8 cases (47%), including seven novel pathogenic variants and one previously reported as being pathogenic. The pathogenic variants were identified in 6 patients with DS (SCN1A gene), one with EIMFS (SCN2A gene), and one with UEE (SLC2A1 gene). Nonrelevant variants were identified in the patients with WS. CONCLUSION: We demonstrated the feasibility of an NGS-gene panel approach for the analysis of patients with EE in our setting. A genetic diagnosis was achieved in nearly 50% of patients, 87% of them presenting with nonpreviously reported variants. The early identification of the underlying causative genetic alteration will be a valuable tool for providing prognostic information and genetic counselling and also to improve therapeutic decisions in Argentinean patients.

Current Progress in Understanding and Recovering the Wheat Genes Lost in Evolution and Domestication.

The modern cultivated wheat has passed a long evolution involving origin of wild emmer (WEM), development of cultivated emmer, formation of spelt wheat and finally establishment of modern bread wheat and durum wheat. During this evolutionary process, rapid alterations and sporadic changes in wheat genome took place, due to hybridization, polyploidization, domestication, and mutation. This has resulted in some modifications and a high level of gene loss. As a result, the modern cultivated wheat does not contain all genes of their progenitors. These lost genes are novel for modern wheat improvement. Exploring wild progenitor for genetic variation of important traits is directly beneficial for wheat breeding. WEM wheat (Triticum dicoccoides) is a great genetic resource with huge diversity for traits. Few genes and quantitative trait loci (QTL) for agronomic, quantitative, biotic and abiotic stress-related traits have already been mapped from WEM. This resource can be utilized for modern wheat improvement by integrating identified genes or QTLs through breeding.

Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice.

Lipid homeostasis is an important component of brain function, and its disturbance causes several neurological disorders, such as Huntington's, Alzheimer's, and Parkinson's diseases as well as mood disorders. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key modulatory molecule involved in lipid homeostasis in the central nervous system. However, little is known about the biological effects of SREBP-1c in the brain. Our previous study uncovered that mice deficient in SREBP-1c exhibit schizophrenia-like behaviors. To investigate whether there are novel molecular mechanisms involved in the neurological aberrations caused by SREBP-1c deficiency, we analyzed the transcriptomes of the hippocampus of SREBP-1c knockout (KO) mice and wild-type mice. We found seven differentially expressed genes (three up-regulated and four down-regulated genes) in the hippocampus of SREBP-1c KO mice. For further verification, we selected the three most significantly changed genes: glucagon-like peptide 2 receptors (GLP2R) involved in hippocampal neurogenesis and neuroplasticity as well as in cognitive impairments; necdin (NDN) which is related to neuronal death and neurodevelopmental disorders; and Erb-B2 receptor tyrosine kinase 4 (ERBB4) which is a receptor for schizophrenia-linked protein, neuregulin-1. The protein levels of GLP2R and NDN were considerably decreased, but the level of ERBB4 was significantly increased in the hippocampus of SREBP-1c KO mice. However, further confirmation is warranted to establish the translatability of these findings from this rodent model into human patients. We suggest that these data provide novel molecular evidence for the modulatory role of SREBP-1c in the mouse hippocampus.

Endocrine and genetic factors affecting egg laying performance in chickens: a review.

1. Egg-laying performance reflects the overall reproductive performance of breeding hens. The genetic traits for egg-laying performance have low or medium heritability, and, depending on the period involved, usually ranges from 0.16 to 0.64. Egg-laying in chickens is regulated by a combination of environmental, endocrine and genetic factors. 2. The main endocrine factors that regulate egg-laying are gonadotropin-releasing hormone (GnRH), prolactin (PRL), follicle-stimulating hormone (FSH) and luteinising hormone (LH). 3. In the last three decades, many studies have explored this aspect at a molecular genetic level. Recent studies identified 31 reproductive hormone-based candidate genes that were significantly associated with egg-laying performance. With the development of genome-sequencing technology, 64 new candidate genes and 108 single nucleotide polymorphisms (SNPs) related to egg-laying performance have been found using genome-wide association studies (GWAS), providing novel insights into the molecular genetic mechanisms governing egg production. At the same time, microRNAs that regulate genes responsible for egg-laying in chickens were reviewed. 4. Research on endocrinological and genetic factors affecting egg-laying performance will greatly improve the reproductive performance of chickens and promote the protection, development, and utilisation of poultry. This review summarises studies on the endocrine and genetic factors of egg-laying performance in chickens from 1972 to 2019.