Sexual dysfunction and cognitive deficits are markers of the aging process. Mammalian sirtuins (SIRT), encoded by sirt 1-7 genes, are known as aging molecules which are sensitive to serotonin (5-hydroxytryptamine, 5-HT). Whether the 5-HT system regulates SIRT in the preoptic area (POA), which could affect reproduction and cognition has not been examined. Therefore, this study was designed to examine the effects of citalopram (CIT, 10 mg/kg for 4 weeks), a potent selective-serotonin reuptake inhibitor and aging on SIRT expression in the POA of male mice using real-time PCR and immunocytochemistry. Age-related increases of sirt1, sirt4, sirt5, and sirt7 mRNA levels were observed in the POA of 52 weeks old mice. Furthermore, 4 weeks of chronic CIT treatment started at 8 weeks of age also increased sirt2 and sirt4 mRNA expression in the POA. Moreover, the number of SIRT4 immuno-reactive neurons increased with aging in the medial septum area (12 weeks = 1.00 ± 0.15 vs. 36 weeks = 1.68 ± 0.14 vs. 52 weeks = 1.54 ± 0.11, p < 0.05). In contrast, the number of sirt4-immunopositive cells did not show a statistically significant change with CIT treatment, suggesting that the increase in sirt4 mRNA levels may occur in cells in which sirt4 is already being expressed. Taken together, these studies suggest that CIT treatment and the process of aging utilize the serotonergic system to up-regulate SIRT4 in the POA as a common pathway to deregulate social cognitive and reproductive functions.
Domestication to captive rearing conditions, along with targeted selective breeding have genetic consequences that vary from those in wild environments. Nile tilapia (Oreochromis niloticus) is one of the most translocated and farmed aquaculture species globally, farmed throughout Asia, North and South America, and its African native range. In Egypt, a breeding program established the Abbassa Strain of Nile tilapia (AS) in 2002 based on local broodstock sourced from the Nile River. The AS has been intensively selected for growth and has gone through genetic bottlenecks which have likely shifted levels and composition of genetic diversity within the strain. Consequently, there are questions on the possible genetic impact AS escapees may have on endemic populations of Nile tilapia. However, to date there have been no genetic studies comparing genetic changes in the domesticated AS to local wild populations. This study used 9,827 genome-wide SNPs to investigate population genetic structure and signatures of selection in the AS (generations 9-11) and eight wild Nile tilapia populations from Egypt. SNP analyses identified two major genetic clusters (captive and wild populations), with wild populations showing evidence of isolation-by-distance among the Nile Delta and upstream riverine populations. Between genetic clusters, approximately 6.9% of SNPs were identified as outliers with outliers identified on all 22 O. niloticus chromosomes. A lack of localized outlier clustering on the genome suggests that no genes of major effect were presently detected. The AS has retained high levels of genetic diversity (Ho_All = 0.21 ± 0.01; He_All = 0.23 ± 0.01) when compared to wild populations (Ho_All = 0.18 ± 0.01; He_All = 0.17 ± 0.01) after 11 years of domestication and selective breeding. Additionally, 565 SNPs were unique within the AS line. While these private SNPs may be due to domestication signals or founder effects, it is suspected that introgression with blue tilapia (Oreochromis aureus) has occurred. This study highlights the importance of understanding the effects of domestication in addition to wild population structure to inform future management and dissemination decisions. Furthermore, by conducting a baseline genetic study of wild populations prior to the dissemination of a domestic line, the effects of aquaculture on these populations can be monitored over time.
Edible bird's nest (EBN) is a popular delicacy in the Asian Pacific region originating from Indonesia, Malaysia, Thailand and Vietnam, which consist of various potential medicine value in Traditional Chinese Medicine (TCM). Thailand is one of the main exporters of EBN. However, the genetic information of EBN, a key part of molecular biology, has yet to be reported in Thailand. It is necessary to explore the genetic information of EBN in Thailand based on a quick and simple method to help protect the rights and interests of consumers. This research aimed to systematically evaluate different methods of extracting EBN DNA to improve the efficiency of the analysis of cytochrome b (Cytb) and NADH dehydrogenase subunit 2 (ND2) gene sequences, the establishment of phylogenetic trees, and the genetic information of EBN in Thailand. Additionally, we aimed to develop a quick and simple method for identifying EBN from different species based on the genetic information and amplification-refractory mutation system PCR (ARMS-PCR). By comparing the four methods [cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), kit and guanidinium isothiocyanate methods] for EBN extraction, we found that the guanidinium isothiocyanate method was the optimal extraction method. Phylogenetic trees generated on the basis of Cytb and ND2 gene analyses showed that 26 samples of house EBN and 4 samples of cave EBN came from Aerodramus fuciphagus and Aerodramus maximus, respectively. In addition, to distinguish different samples from different species of Apodiformes, we designed 4 polymerase chain reaction (PCR) amplification primers based on the ND2 gene sequences of A. fuciphagus and A. maximus. The ARMS-PCR results showed band lengths for A. fuciphagus EBN of 533, 402, and 201 bp, while those for A. maximus EBN were 463, 317, and 201 bp. Collectively, the results showed that ARMS-PCR is a fast and simple method for the genetic identification of EBN based on designing specific original identification primers.
Genetic testing aids patients in making important decisions in the prevention, treatment, or early detection of hereditary disorders. Low awareness of the importance of genetic testing contributes to the increase in the incidence of hereditary disorders. This study aims to explore the knowledge, awareness, and perception of genetic testing for hereditary disorders among local residents of the Klang Valley, Malaysia, and the potential variables that influence their understanding of genetic testing. A survey was conducted in different municipalities of the Klang Valley through self-administered questionnaire assessing the public's knowledge, awareness, and perception of genetic testing. Overall, the results revealed adequate knowledge and positive awareness of genetic testing, in which both were influenced by the respondent's educational level (P < 0.001), field of study (P < 0.001), and status of heard or unheard of genetic testing (P < 0.001). The perception of genetic testing was generally positive and influenced by the respondent's differences in age (P < 0.016), educational level (P < 0.001), field of study (P < 0.001), and status of heard or unheard of genetic testing (P < 0.001). Although positive responses were obtained, ~20.2% of the respondents had never heard of genetic testing. Of the respondents, 24.5% were unwilling to undergo genetic testing, with 25.1% believing that genetic testing tampers with nature and 18% believing that it opposes religion and their beliefs. Such attitude calls for the need to conduct programs to eliminate any misconception, as well as to educate the public to lessen any perceived misunderstanding of the concepts of genetic testing.
Mud crab, Scylla paramamosain is one of the most important crustacean species in global aquaculture. To determine the genetic basis of sex and growth-related traits in S. paramamosain, a high-density genetic linkage map with 16,701 single nucleotide polymorphisms (SNPs) was constructed using SLAF-seq and a full-sib family. The consensus map has 49 linkage groups, spanning 5,996.66 cM with an average marker-interval of 0.81 cM. A total of 516 SNP markers, including 8 female-specific SNPs segregated in two quantitative trait loci (QTLs) for phenotypic sex were located on LG32. The presence of female-specific SNP markers only on female linkage map, their segregation patterns and lower female: male recombination rate strongly suggest the conformation of a ZW/ZZ sex determination system in S. paramamosain. The QTLs of most (90%) growth-related traits were found within a small interval (25.18-33.74 cM) on LG46, highlighting the potential involvement of LG46 in growth. Four markers on LG46 were significantly associated with 10-16 growth-related traits. BW was only associated with marker 3846. Based on the annotation of transcriptome data, 11 and 2 candidate genes were identified within the QTL regions of sex and growth-related traits, respectively. The newly constructed high-density genetic linkage map with sex-specific SNPs, and the identified QTLs of sex- and growth-related traits serve as a valuable genetic resource and solid foundation for marker-assisted selection and genetic improvement of crustaceans.
Accurately measuring the phenotype at the individual level is critical to the success of selective breeding programs. Feed efficiency is a key sustainability trait and is typically approached through feed conversion ratio (FCR). This requires measurements of body weight gain (BWG) and feed intake (FI), the latter being technically challenging in fish. We assessed two of the principal methods for measuring feed intake in fish over consecutive days: (1) group rearing 10 fish per group and video recording the meals and (2) rearing fish individually on a restricted ration. Juvenile Nile tilapia (Oreochromis niloticus) from the Genetically Improved Farmed Tilapia (GIFT) strain and the Cirad strain were entered into the study (128 GIFT and 109 Cirad). The GIFT strain were reared over three consecutive periods of 7 days each under different feeding, recording, and rearing scenarios (i) in groups fed an optimal ration (g100) or (ii) fed a 50% restricted ration (g50) both with video records of all meals and (iii) reared in isolation and fed a 50% restrictive ration. The Cirad strain were tested similarly but only for scenarios (i) and (iii). All fish were fed twice daily with a calculated ration. Correlations showed the same trends for the GIFT and the Cirad strains. For the GIFT strain, correlations were positive and significant for BWG and FI measured in scenarios (i) and (ii), 0.49 and 0.63, respectively, and FI measured in scenarios (i) and (iii) (0.50) but not for BWG measured in scenarios (i) and (iii) (0.29, NS). The phenotypic correlation estimated for FCR between scenarios (i) and (ii) with fish fed an optimal or a 50% restricted ration was low and not significant (0.22). Feed Conversion Ratio for GIFT fish reared in groups or in isolation and fed with a restricted ration [scenarios (ii) and (iii)] were not significantly correlated either. Social interactions between fish, potentially impacting their efficiency, may explain the results. Therefore, selective breeding programs seeking to improve feed efficiency will need to carefully plan the feeding rate and the rearing system used to estimate FCR in order to optimize selection for the targeted production system.
The extent to which genetic gain achieved from selection programs under strictly controlled environments in the nucleus that can be expressed in commercial production systems is not well-documented in aquaculture species. The main aim of this paper was to assess the effects of genotype by environment interaction on genetic response and genetic parameters for four body traits (harvest weight, standard length, body depth, body width) and survival in Red tilapia (Oreochromis spp.). The growth and survival data were recorded on 19,916 individual fish from a pedigreed population undergoing three generations of selection for increased harvest weight in earthen ponds from 2010 to 2012 at the Aquaculture Extension Center, Department of Fisheries, Jitra in Kedah, Malaysia. The pedigree comprised a total of 224 sires and 262 dams, tracing back to the base population in 2009. A multivariate animal model was used to measure genetic response and estimate variance and covariance components. When the homologous body traits in freshwater pond and cage were treated as genetically distinct traits, the genetic correlations between the two environments were high (0.85-0.90) for harvest weight and square root of harvest weight but the estimates were of lower magnitudes for length, width and depth (0.63-0.79). The heritabilities estimated for the five traits studied differed between pond (0.02 to 0.22) and cage (0.07 to 0.68). The common full-sib effects were large, ranging from 0.23 to 0.59 in pond and 0.11 to 0.31 in cage across all traits. The direct and correlated responses for four body traits were generally greater in pond than in cage environments (0.011-1.561 vs. -0.033-0.567 genetic standard deviation units, respectively). Selection for increased harvest body weight resulted in positive genetic changes in survival rate in both pond and cage culture. In conclusion, the reduced selection response and the magnitude of the genetic parameter estimates in the production environment (i.e., cage) relative to those achieved in the nucleus (pond) were a result of the genotype by environment interaction and this effect should be taken into consideration in the future breeding program for Red tilapia.
Psoriasis is multifactorial disease with complex genetic predisposition. Recent advances in genetics and genomics analyses have provided many insights into the relationship between specific genetic predisposition and the immunopathological mechanisms driving psoriasis manifestation. Novel approaches which utilize array-based genotyping technologies such as genome-wide association studies and bioinformatics tools for transcriptomics analysis have identified single nucleotide polymorphisms, genes and pathways that are associated with psoriasis. The discovery of these psoriasis-associated susceptibility loci, autoimmune targets and altered signaling pathways have provided opportunities to bridge the gap of knowledge from sequence to consequence, allowing new therapeutic strategies for the treatment of psoriasis to be developed. Here, we discuss recent advances in the field by highlighting how immune functions associated with psoriasis susceptibility loci may contribute to disease pathogenesis in different populations. Understanding the genetic variations in psoriasis and how these may influence the immunological pathways to cause disease will contribute to the efforts in developing novel and targeted personalized therapies for psoriasis patients.
There is a growing attention toward personalized medicine. This is led by a fundamental shift from the 'one size fits all' paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data "10 Vs" and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine.
Circular RNAs (circRNAs) which were once considered as "junk" are now in the spotlight as a potential player in regulating human diseases, especially cancer. With the development of high throughput technologies in recent years, the full potential of circRNAs is being uncovered. CircRNAs possess some unique characteristics and advantageous properties that could benefit medical research and clinical applications. CircRNAs are stable with covalently closed loops that are resistant to ribonucleases, have disease stage-specific expressions and are selectively abundant in different types of tissues. Interestingly, the presence of circRNAs in different types of treatment resistance in human cancers was recently observed with the involvement of a few key pathways. The activation of certain pathways by circRNAs may give new insights to treatment resistance management. The potential usage of circRNAs from this aspect is very much in its infancy stage and has not been fully validated. This mini-review attempts to highlight the possible role of circRNAs as regulators of treatment resistance in human cancers based on its intersection molecules and cancer-related regulatory networks.
Overexpression of MSN2, which is the transcription factor gene in response to stress, is well-known to increase the tolerance of the yeast Saccharomyces cerevisiae cells to a wide variety of environmental stresses. Recent studies have found that the Msn2 is a feasible potential mediator of proline homeostasis in yeast. This result is based on the finding that overexpression of the MSN2 gene exacerbates the cytotoxicity of yeast to various amino acid analogs whose uptake is increased by the active amino acid permeases localized on the plasma membrane as a result of a dysfunctional deubiquitination process. Increased understanding of the cellular responses induced by the Msn2-mediated proline incorporation will provide better comprehension of how cells respond to and counteract to different kinds of stimuli and will also contribute to the breeding of industrial yeast strains with increased productivity.
Southeast Asia (SEA) has one of the longest records of modern human habitation out-of-Africa. Located at the crossroad of the mainland and islands of SEA, Peninsular Malaysia is an important piece of puzzle to the map of peopling and migration history in Asia, a question that is of interest to many anthropologists, archeologists, and population geneticists. This review aims to revisit our understanding to the population genetics of the natives from Peninsular Malaysia and Borneo over the past century based on the chronology of the technology advancement: 1) Anthropological and Physical Characterization; 2) Blood Group Markers; 3) Protein Markers; 4) Mitochondrial and Autosomal DNA Markers; and 5) Whole Genome Analysis. Subsequently some missing gaps of the study are identified. In the later part of this review, challenges of studying the population genetics of natives will be elaborated. Finally, we conclude our review by reiterating the importance of unveiling migration history and genetic diversity of the indigenous populations as a steppingstone towards comprehending disease evolution and etiology.
Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.
Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry. Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0-4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations. Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10-17), centric rings (p = 4.0310-14), and resulting double-strand-breaks (DSB) (p = 1.32 10-18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa. Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.
The recent research and technology development in medical genomics has raised new issues that are profoundly different from those encountered in traditional clinical research for which informed consent was developed. Global initiatives for international collaboration and public participation in genomics research now face an increasing demand for new forms of informed consent which reflect local contexts. This article analyzes informed consent forms (ICFs) for genomic research formulated by four selected research programs and institutes in East Asia - the Medical Genome Science Program in Japan, Universiti Sains Malaysia Human Research Ethics Committee in Malaysia, and the Taiwan Biobank and the Taipei Medical University- Joint Institutional Review Board in Taiwan. The comparative text analysis highlights East Asian contexts as distinct from other regions by identifying communicative and social functions of consent forms. The communicative functions include re-contact options and offering interactive support for research participants, and setting opportunities for family or community engagement in the consent process. This implies that informed consent cannot be validated solely with the completion of a consent form at the initial stage of the research, and informed consent templates can facilitate interactions between researchers and participants through (even before and after) the research process. The social functions consist of informing participants of possible social risks that include genetic discrimination, sample and data sharing, and highlighting the role of ethics committees. Although international ethics harmonization and the subsequent coordination of consent forms may be necessary to maintain the quality and consistency of consent process for data-intensive international research, it is also worth paying more attention to the local values and different settings that exist where research participants are situated for research in medical genomics. More than simply tools to gain consent from research participants, ICFs function rather as a device of social communication between research communities and civic communities in liaison with intermediary agents like ethics committees, genetic counselors, and public biobanks and databases.
Wound healing is a complex biological process that is generally composed of four phases: hemostasis, inflammation, proliferation, and remodeling. The proliferation phase is crucial for effective healing compared to other phases. Many critical events occur during this phase, i.e., migration of fibroblasts, re-epithelialization, angiogenesis and wound contraction. Chronic wounds are common and are considered a major public health problem. Therefore, there is the increasing need to discover new therapeutic strategies. MicroRNA (miRNA) research in the field of wound healing is in its early phase, but the knowledge of the recent discoveries is essential for developing effective therapies for the treatment of chronic wounds. In this review, we focused on recently discovered miRNAs which are involved in the proliferation phase of wound healing in the past few years and their role in wound healing.
Myotonia congenita (MC) is a rare neuromuscular disease caused by mutations within the CLCN1 gene encoding skeletal muscle chloride channels. MC is characterized by delayed muscle relaxation during contraction, resulting in muscle stiffness. There is a lack of MC case reports and data on the prevalence among Malaysians. We report a clinical case of a 50-year-old woman presents with muscle stiffness and cramp episodes that started in early childhood. She had difficulty initiating muscle movement and presented with transient muscle weakness after rest, which usually improved after repeated contraction (warm-up phenomenon). She was diagnosed with MC after myotonic discharge on electromyography (EMG). Her brother had similar symptoms; however, no additional family members showed MC symptoms. Serum creatine kinase levels were elevated in both the proband and her brother with 447 U/L and 228 U/L recorded, respectively. Genetic analysis by whole-exome sequencing (WES) revealed a previously reported pathogenic CLCN1 gene variant c.1667T>A (p.I556N). Genetic screening of all family members revealed that the same variant was observed in the children of both the proband and her brother; however, the children did not present with either clinical or electrophysiological MC symptoms. The multiplex ligation-dependent probe amplification (MLPA) analysis conducted identified neither exon deletion nor duplication in CLCN1. In conclusion, this report describes the first case of MC in Malaysia in which incomplete penetrance observed in this family is caused by a known pathogenic CLCN1 variant.