Genomic Prediction for Whole Weight, Body Shape, Meat Yield, and Color Traits in the Portuguese Oyster Crassostrea angulata.

Genetic improvement for quality traits, especially color and meat yield, has been limited in aquaculture because the assessment of these traits requires that the animals be slaughtered first. Genotyping technologies do, however, provide an opportunity to improve the selection efficiency for these traits. The main purpose of this study is to assess the potential for using genomic information to improve meat yield (soft tissue weight and condition index), body shape (cup and fan ratios), color (shell and mantle), and whole weight traits at harvest in the Portuguese oyster, Crassostrea angulata. The study consisted of 647 oysters: 188 oysters from 57 full-sib families from the first generation and 459 oysters from 33 full-sib families from the second generation. The number per family ranged from two to eight oysters for the first and 12-15 oysters for the second generation. After quality control, a set of 13,048 markers were analyzed to estimate the genetic parameters (heritability and genetic correlation) and predictive accuracy of the genomic selection for these traits. The multi-locus mixed model analysis indicated high estimates of heritability for meat yield traits: 0.43 for soft tissue weight and 0.77 for condition index. The estimated genomic heritabilities were 0.45 for whole weight, 0.24 for cup ratio, and 0.33 for fan ratio and ranged from 0.14 to 0.54 for color traits. The genetic correlations among whole weight, meat yield, and body shape traits were favorably positive, suggesting that the selection for whole weight would have beneficial effects on meat yield and body shape traits. Of paramount importance is the fact that the genomic prediction showed moderate to high accuracy for the traits studied (0.38-0.92). Therefore, there are good prospects to improve whole weight, meat yield, body shape, and color traits using genomic information. A multi-trait selection program using the genomic information can boost the genetic gain and minimize inbreeding in the long-term for this population.

Genetic links between endometriosis and cancers in women.

Endometriosis is a chronic disease occurring during the reproductive stage of women. Although there is only limited association between endometriosis and gynecological cancers with regard to clinical features, the molecular basis of the relationship between these diseases is unexplored. We conducted a systematic study by integrating literature-based evidence, gene expression and large-scale cancer genomics data in order to reveal any genetic relationships between endometriosis and cancers in women. We curated 984 endometriosis-related genes from 3270 PubMed articles and then conducted a meta-analysis of the two public gene expression profiles related to endometriosis which identified Differential Expression of Genes (DEGs). Following an overlapping analysis, we identified 39 key endometriosis-related genes common in both literature and DEG analysis. Finally, the functional analysis confirmed that all the 39 genes were associated with the vital processes of tumour formation and cancer progression and that two genes (PGR and ESR1) were common to four cancers of women. From network analysis, we identified a novel linker gene, C3AR1, which had not been implicated previously in endometriosis. The shared genetic mechanisms of endometriosis and cancers in women identified in this study provided possible new avenues of multiple disease management and treatments through early diagnosis.

Integrative analysis of common genes and driver mutations implicated in hormone stimulation for four cancers in women.

Cancer is one of the leading cause of death of women worldwide, and breast, ovarian, endometrial and cervical cancers contribute significantly to this every year. Developing early genetic-based diagnostic tools may be an effective approach to increase the chances of survival and provide more treatment opportunities. However, the current cancer genetic studies are mainly conducted independently and, hence lack of common driver genes involved in cancers in women. To explore the potential common molecular mechanism, we integrated four comprehensive literature-based databases to explore the shared implicated genetic effects. Using a total of 460 endometrial, 2,068 ovarian, 2,308 breast and 537 cervical cancer-implicated genes, we identified 52 genes which are common in all four types of cancers in women. Furthermore, we defined their potential functional role in endogenous hormonal regulation pathways within the context of four cancers in women. For example, these genes are strongly associated with hormonal stimulation, which may facilitate rapid diagnosis and treatment management decision making. Additional mutational analyses on combined the cancer genome atlas datasets consisting of 5,919 gynaecological and breast tumor samples were conducted to identify the frequently mutated genes across cancer types. For those common implicated genes for hormonal stimulants, we found that three quarter of 5,919 samples had genomic alteration with the highest frequency in MYC (22%), followed by NDRG1 (19%), ERBB2 (14%), PTEN (13%), PTGS2 (13%) and CDH1 (11%). We also identified 38 hormone related genes, eight of which are associated with the ovulation cycle. Further systems biology approach of the shared genes identified 20 novel genes, of which 12 were involved in the hormone regulation in these four cancers in women. Identification of common driver genes for hormone stimulation provided an unique angle of involving the potential of the hormone stimulants-related genes for cancer diagnosis and prognosis.

The pan-cancer analysis of gain-of-functional mutations to identify the common oncogenic signatures in multiple cancers.

Oncogenes can potentially cause uncontrolled cell growth, leading to cancer development, and these genes are normally mutated and over-expressed in tumor cells. Genomic alteration of oncogenes might result in oncogenesis and promotion of cancer progression. To date, researchers have focused mainly on the roles of oncogenes in particular cancers, but investigation of oncogenes with gain-of-function mutations in multiple cancer types are less represented in the literature. Furthermore, the effect of those gain-of-function are not validated in gene expression level. To meet this demand, we performed a systematic analysis of gene expression in oncogenes to identify the occurrence of gain-of-function mutations in pan-cancer. We identified 33,551 oncogenic mutations in 5000 samples. From our analysis, we identified three tissues with the highest frequency of gain-of-functional oncogenic mutations in hundreds of samples: breast (739 samples), central nervous system (646 samples) and large intestine (498 samples). By further counting the number of occurrences of oncogenes across cancer types, we identified a list cross-cancer mutational signatures of 99 oncogenes highly mutated in >400 samples in breast, central nervous system and large intestine samples. By further overlapping with gene expression data in the matched tumor samples, we further identified 1875 gain-of-functional mutations/events with consistent gene up-regulation in 1031 samples from multiple cancers. This result may offer additional insight into the relationship between gene dosage and oncogenesis and maybe useful in targeted cancer therapy. In summary, this study provides the first globally examining on the genetic alteration of oncogenes across cancer types. Clinical association analysis has shown that these 99 genes have a significant effect on survival.

The bioinformatics tools for the genome assembly and analysis based on third-generation sequencing.

The application of third-generation sequencing (TGS) technology in genetics and genomics have provided opportunities to categorize and explore the individual genomic landscapes and mutations relevant for diagnosis and therapy using whole genome sequencing and de novo genome assembly. In general, the emerging TGS technology can produce high quality long reads for the determination of overlapping reads and transcript isoforms. However, this technology still faces challenges such as the accuracy for the identification of nucleotide bases and high error rates. Here, we surveyed 39 TGS-related tools for de novo assembly and genome analysis to identify the differences among their characteristics, such as the required input, the interaction with the user, sequencing platforms, type of reads, error models, the possibility of introducing coverage bias, the simulation of genomic variants and outputs provided. The decision trees are summarized to help researchers to find out the most suitable tools to analyze the TGS data. Our comprehensive survey and evaluation of computational features of existing methods for TGS may provide a valuable guideline for researchers.

Cold acclimation in the moss Physcomitrella patens involves abscisic acid-dependent signaling.

Overwintering plants develop tolerance to freezing stress through a cold acclimation process by which the cells provoke internal protective mechanisms against freezing. The stress hormone abscisic acid (ABA) is known to increase freezing tolerance of plant cells, but its role in cold acclimation has not been determined. In this study, we used ABA-insensitive lines of the moss Physcomitrella patens to determine whether cold acclimation in bryophytes involves an ABA-dependent process. Two ABA-insensitive lines, both impaired in ABA signaling without showing ABA-induced stress tolerance, were subjected to cold acclimation, and changes in freezing tolerance and accumulation of soluble sugars and proteins were compared to the wild type. The wild-type cells acquired freezing tolerance in response to cold acclimation treatment, but very little increase in freezing tolerance was observed in the ABA-insensitive lines. Analysis of low-molecular-weight soluble sugars indicated that the ABA-insensitive lines accumulated sucrose, a major compatible solute in bryophytes, to levels comparable with those of the wild type during cold acclimation. However, accumulation of the trisaccharide theanderose and of specific LEA-like boiling-soluble proteins was very limited in the ABA-insensitive lines. Furthermore, analysis of cold-induced expression of genes encoding LEA-like proteins revealed that the ABA-insensitive lines accumulate only small amounts of these transcripts during cold acclimation. Our results indicate that cold acclimation of bryophytes requires an ABA-dependent signaling process. The results also suggest that cold-induced sugar accumulation, depending on the sugar species, can either be dependent or independent of the ABA-signaling pathway.

Evolutionarily conserved regulatory mechanisms of abscisic acid signaling in land plants: characterization of ABSCISIC ACID INSENSITIVE1-like type 2C protein phosphatase in the liverwort Marchantia polymorpha.

Abscisic acid (ABA) is postulated to be a ubiquitous hormone that plays a central role in seed development and responses to environmental stresses of vascular plants. However, in liverworts (Marchantiophyta), which represent the oldest extant lineage of land plants, the role of ABA has been least emphasized; thus, very little information is available on the molecular mechanisms underlying ABA responses. In this study, we isolated and characterized MpABI1, an ortholog of ABSCISIC ACID INSENSITIVE1 (ABI1), from the liverwort Marchantia polymorpha. The MpABI1 cDNA encoded a 568-amino acid protein consisting of the carboxy-terminal protein phosphatase 2C (PP2C) domain and a novel amino-terminal regulatory domain. The MpABI1 transcript was detected in the gametophyte, and its expression level was increased by exogenous ABA treatment in the gemma, whose growth was strongly inhibited by ABA. Experiments using green fluorescent protein fusion constructs indicated that MpABI1 was mainly localized in the nucleus and that its nuclear localization was directed by the amino-terminal domain. Transient overexpression of MpABI1 in M. polymorpha and Physcomitrella patens cells resulted in suppression of ABA-induced expression of the wheat Em promoter fused to the beta -glucuronidase gene. Transgenic P. patens expressing MpABI1 and its mutant construct, MpABI1-d2, lacking the amino-terminal domain, had reduced freezing and osmotic stress tolerance, and associated with reduced accumulation of ABA-induced late embryogenesis abundant-like boiling-soluble proteins. Furthermore, ABA-induced morphological changes leading to brood cells were not prominent in these transgenic plants. These results suggest that MpABI1 is a negative regulator of ABA signaling, providing unequivocal molecular evidence of PP2C-mediated ABA response mechanisms functioning in liverworts.