Recent advances and future perspectives in early-maturing cotton research.

Cotton's fundamental requirements for long periods of growth and specific seasonal temperatures limit the global arable areas that can be utilized to cultivate cotton. This constraint can be alleviated by breeding for early-maturing varieties. By delaying the sowing dates without impacting the boll-opening time, early-maturing varieties not only mitigate the yield losses brought on by unfavorable weathers in early spring and late autumn but also help reducing the competition between cotton and other crops for arable land, thereby optimizing the cropping system. This review presents studies and breeding efforts for early-maturing cotton, which efficiently pyramid early maturity, high-quality, multiresistance traits, and suitable plant architecture by leveraging pleiotropic genes. Attempts are also made to summarize our current understanding of the molecular mechanisms underlying early maturation, which involves many pathways such as epigenetic, circadian clock, and hormone signaling pathways. Moreover, new avenues and effective measures are proposed for fine-scale breeding of early-maturing crops to ensure the healthy development of the agricultural industry.

Pleiotropic architectures of porcine immune and growth trait pairs revealed by a self-product-based transcriptome method.

Pleiotropy is an important biological phenomenon with complicated genetic architectures for multiple traits. To date, pleiotropy has been mainly identified by multi-trait genome-wide association studies, but this method has its disadvantages, and new developments for pleiotropy detection methods are needed. Here we define a novel metric, self-product, to measure individual-level co-variation of two traits, and develop a novel self-product-based transcriptome method to detect pleiotropic genes (PGs). Our method was tested using four immune-growth trait pairs and four immune-immune trait pairs in pigs. Comparative transcriptome analyses identified hundreds of candidate PGs related to eight trait pairs from two tails of self-product distribution. Gene Ontology enrichment analysis indicated that most of identified PGs were involved in immune- or growth-related biological processes. We established PG interaction networks to exhibit core genes shared by eight trait pairs, of which CCL5 and IL-10 genes were the hub genes. Genetic association analyses showed that SmaI-polymorphisms of CCL5 and IL-10 genes had significant associations with phenotypic co-variations of multiple trait pairs, indicating that the variants in pleiotropic genes were also pleiotropic variants. Taken together, the validity of our proposed method was preliminarily verified, and our findings provide new insights into the genetic basis of pleiotropic architectures of immune and growth trait pairs in pigs.

Translational aspects of novel findings in genetics of male infertility-status quo 2021.

INTRODUCTION: Male factor infertility concerns 7-10% of men and among these 40-60% remain unexplained. SOURCES OF DATA: This review is based on recent published literature regarding the genetic causes of male infertility. AREAS OF AGREEMENT: Screening for karyotype abnormalities, biallelic pathogenic variants in the CFTR gene and Y-chromosomal microdeletions have been routine in andrology practice for >20 years, explaining ~10% of infertility cases. Rare specific conditions, such as congenital hypogonadotropic hypogonadism, disorders of sex development and defects of sperm morphology and motility, are caused by pathogenic variants in recurrently affected genes, which facilitate high diagnostic yield (40-60%) of targeted gene panel-based testing. AREAS OF CONTROVERSY: Progress in mapping monogenic causes of quantitative spermatogenic failure, the major form of male infertility, has been slower. No 'recurrently' mutated key gene has been identified and worldwide, a few hundred patients in total have been assigned a possible monogenic cause. GROWING POINTS: Given the high genetic heterogeneity, an optimal approach to screen for heterogenous genetic causes of spermatogenic failure is sequencing exomes or in perspective, genomes. Clinical guidelines developed by multidisciplinary experts are needed for smooth integration of expanded molecular diagnostics in the routine management of infertile men. AREAS TIMELY FOR DEVELOPING RESEARCH: Di-/oligogenic causes, structural and common variants implicated in multifactorial inheritance may explain the 'hidden' genetic factors. It is also critical to understand how the recently identified diverse genetic factors of infertility link to general male health concerns across lifespan and how the clinical assessment could benefit from this knowledge.

A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population.

BACKGROUND: Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive as it is likely to be interfered with by substantial confounding factors and potential reverse causality. The present study aimed to investigate causal correlation of the two diseases by a Mendelian randomization (MR) study and further elucidate the underlying molecular mechanisms. METHODS: With the biggest summary datasets of a genome-wide association study (GWAS) in the East Asian population, we conducted a two-sample, bidirectional MR study to assess the causal correlation between shrimp allergy (SA) and MDD. Subsequently, we identified the pleiotropic genes' susceptibility to the two diseases at whole-genome and tissue-specific levels, respectively. Enriched GO sets and KEGG pathways were also discovered to elucidate the potential underlying mechanisms. RESULTS: With the most suitable MR method, SA was identified as a causal risk factor for MDD based on three different groups of independent genetic instruments, respectively (p < 2.81 × 10-2). In contrast, we did not observe a significant causal effect of MDD on SA. The GWAS-pairwise program successfully identified seven pleiotropic genetic variants (PPA3 > 0.8), indicating that the two diseases indeed have a shared genetic basis. At a whole-genome level, the MAGMA program identified 44 pleiotropic genes, which were enriched in allergy-related pathways, such as antigen processing and presentation pathway (p = 1.46 × 10-2). In brain-specific tissue, the S-MultiXcan program found 17 pleiotropic genes that were significantly enriched in immune-related pathways and GO sets, including asthma-related pathway, T-cell activation-related, and major histocompatibility complex protein-related GO sets. Regarding whole-blood tissue, the program identified six pleiotropic genes that are significantly enriched in tolerance induction-related GO sets. CONCLUSIONS: The present study for the first time indicated a significant causal effect of SA on the occurrence of MDD, but the reverse was not true. Enrichment analyses of pleiotropic genes at whole-genome and tissue-specific levels implied the involvement of allergy and immune-related pathways in the shared genetic mechanism of the two diseases. Elucidating the causal effect and the acting direction may be beneficial in reducing the incidence rate of MDD for the massive group of SA patients in the East Asian region.

The Youngest, the Heaviest and/or the Darkest? Selection Potentialities and Determinants of Leadership in Canarian Dromedary Camels.

Several idiosyncratic and genetically correlated traits are known to extensively influence leadership in both domestic and wild species. For minor livestock such as camels, however, this type of behavior remains loosely defined and approached only for sex-mixed herds. The interest in knowing those animal-dependent variables that make an individual more likely to emerge as a leader in a single-sex camel herd has its basis in the sex-separated breeding of Canarian dromedary camels for utilitarian purposes. By means of an ordinal logistic regression, it was found that younger, gelded animals may perform better when eliciting the joining of mates, assuming that they were castrated just before reaching sexual maturity and once they were initiated in the pertinent domestication protocol for their lifetime functionality. The higher the body weight, the significantly (p < 0.05) higher the score in the hierarchical rank when leading group movements, although this relationship appeared to be inverse for the other considered zoometric indexes. Camels with darker and substantially depigmented coats were also significantly (p < 0.05) found to be the main initiators. Routine intraherd management and leisure tourism will be thus improved in efficiency and security through the identification and selection of the best leader camels.

Detection of Genetic Overlap Between Rheumatoid Arthritis and Systemic Lupus Erythematosus Using GWAS Summary Statistics.

BACKGROUND: Clinical and epidemiological studies have suggested systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are comorbidities and common genetic etiologies can partly explain such coexistence. However, shared genetic determinations underlying the two diseases remain largely unknown. METHODS: Our analysis relied on summary statistics available from genome-wide association studies of SLE (N = 23,210) and RA (N = 58,284). We first evaluated the genetic correlation between RA and SLE through the linkage disequilibrium score regression (LDSC). Then, we performed a multiple-tissue eQTL (expression quantitative trait loci) weighted integrative analysis for each of the two diseases and aggregated association evidence across these tissues via the recently proposed harmonic mean P-value (HMP) combination strategy, which can produce a single well-calibrated P-value for correlated test statistics. Afterwards, we conducted the pleiotropy-informed association using conjunction conditional FDR (ccFDR) to identify potential pleiotropic genes associated with both RA and SLE. RESULTS: We found there existed a significant positive genetic correlation (r g = 0.404, P = 6.01E-10) via LDSC between RA and SLE. Based on the multiple-tissue eQTL weighted integrative analysis and the HMP combination across various tissues, we discovered 14 potential pleiotropic genes by ccFDR, among which four were likely newly novel genes (i.e., INPP5B, OR5K2, RP11-2C24.5, and CTD-3105H18.4). The SNP effect sizes of these pleiotropic genes were typically positively dependent, with an average correlation of 0.579. Functionally, these genes were implicated in multiple auto-immune relevant pathways such as inositol phosphate metabolic process, membrane and glucagon signaling pathway. CONCLUSION: This study reveals common genetic components between RA and SLE and provides candidate associated loci for understanding of molecular mechanism underlying the comorbidity of the two diseases.

Virus infection of the CNS disrupts the immune-neural-synaptic axis via induction of pleiotropic gene regulation of host responses.

Treatment for many viral infections of the central nervous system (CNS) remains only supportive. Here we address a remaining gap in our knowledge regarding how the CNS and immune systems interact during viral infection. By examining the regulation of the immune and nervous system processes in a nonhuman primate model of West Nile virus neurological disease, we show that virus infection disrupts the homeostasis of the immune-neural-synaptic axis via induction of pleiotropic genes with distinct functions in each component of the axis. This pleiotropic gene regulation suggests an unintended off-target negative impact of virus-induced host immune responses on the neurotransmission, which may be a common feature of various viral infections of the CNS.

Shared genes between Alzheimer's disease and ischemic stroke.

AIMS: Although converging evidence from experimental and epidemiological studies indicates Alzheimer's disease (AD) and ischemic stroke (IS) are related, the genetic basis underlying their links is less well characterized. Traditional SNP-based genome-wide association studies (GWAS) have failed to uncover shared susceptibility variants of AD and IS. Therefore, this study was designed to investigate whether pleiotropic genes existed between AD and IS to account for their phenotypic association, although this was not reported in previous studies. METHODS: Taking advantage of large-scale GWAS summary statistics of AD (17,008 AD cases and 37,154 controls) and IS (10,307 IS cases and 19,326 controls), we performed gene-based analysis implemented in VEGAS2 and Fisher's meta-analysis of the set of overlapped genes of nominal significance in both diseases. Subsequently, gene expression analysis in AD- or IS-associated expression datasets was conducted to explore the transcriptional alterations of pleiotropic genes identified. RESULTS: 16 AD-IS pleiotropic genes surpassed the cutoff for Bonferroni-corrected significance. Notably, MS4A4A and TREM2, two established AD-susceptibility genes showed remarkable alterations in the spleens and brains afflicted by IS, respectively. Among the prioritized genes identified by virtue of literature-based knowledge, most are immune-relevant genes (EPHA1, MS4A4A, UBE2L3 and TREM2), implicating crucial roles of the immune system in the pathogenesis of AD and IS. CONCLUSIONS: The observation that AD and IS had shared disease-associated genes offered mechanistic insights into their common pathogenesis, predominantly involving the immune system. More importantly, our findings have important implications for future research directions, which are encouraged to verify the involvement of these candidates in AD and IS and interpret the exact molecular mechanisms of action.

The genetic pleiotropy of musculoskeletal aging.

Musculoskeletal aging is detrimental to multiple bodily functions and starts early, probably in the fourth decade of an individual's life. Sarcopenia is a health problem that is expected to only increase as a greater portion of the population lives longer; prevalence of the related musculoskeletal diseases is similarly expected to increase. Unraveling the biological and biomechanical associations and molecular mechanisms underlying these diseases represents a formidable challenge. There are two major problems making disentangling the biological complexity of musculoskeletal aging difficult: (a) it is a systemic, rather than "compartmental," problem, which should be approached accordingly, and (b) the aging per se is neither well defined nor reliably measurable. A unique challenge of studying any age-related condition is a need of distinguishing between the "norm" and "pathology," which are interwoven throughout the aging organism. We argue that detecting genes with pleiotropic functions in musculoskeletal aging is needed to provide insights into the potential biological mechanisms underlying inter-individual differences insusceptibility to the musculoskeletal diseases. However, exploring pleiotropic relationships among the system's components is challenging both methodologically and conceptually. We aimed to focus on genetic aspects of the cross-talk between muscle and its "neighboring" tissues and organs (tendon, bone, and cartilage), and to explore the role of genetics to find the new molecular links between skeletal muscle and other parts of the "musculoskeleton." Identification of significant genetic variants underlying the musculoskeletal system's aging is now possible more than ever due to the currently available advanced genomic technologies. In summary, a "holistic" genetic approach is needed to study the systems's normal functioning and the disease predisposition in order to improve musculoskeletal health.