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Fulltext Hemoglobin A2 and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene

Mahmud N, Maffei M, Mogni M, Forni GL, Pinto VM, Barberio G, et al.

Genes (Basel), 2021 11 19;12(11).
PMID: 34828427 DOI: 10.3390/genes12111821

BACKGROUND: Hemoglobin A (Hb A) (α2β2) in the normal adult subject constitutes 96-98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A2 (Hb A2) (α2δ2), the normal reference values are between 2.0 and 3.3%. It is important to evaluate the presence of possible delta gene mutations in a population at high risk for globin gene defects in order to correctly diagnose the β-thalassemia carrier.
METHODS: The most used methods for the quantification of Hb A2 are based on automated high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). In particular Hb analyses were performed by HPLC on three dedicated devices. DNA analyses were performed according to local standard protocols.
RESULTS: Here, we described eight new δ-globin gene variants discovered and characterized in some laboratories in Northern Italy in recent years. These new variants were added to the many already known Hb A2 variants that were found with an estimated frequency of about 1-2% during the screening tests in our laboratories.
CONCLUSIONS: The knowledge recognition of the delta variant on Hb analysis and accurate molecular characterization is crucial to provide an accurate definitive thalassemia diagnosis, particularly in young subjects who would like to ask for a prenatal diagnosis or preimplantation genetic diagnosis.
Fulltext Identification and Analysis of microRNAs in Chlorella sorokiniana Using High-Throughput Sequencing

Azaman SNA, Satharasinghe DA, Tan SW, Nagao N, Yusoff FM, Yeap SK

Genes (Basel), 2020 09 25;11(10).
PMID: 32992970 DOI: 10.3390/genes11101131

Chlorella is a popular microalga with robust physiological and biochemical characteristics, which can be cultured under various conditions. The exploration of the small RNA content of Chlorella could improve strategies for the enhancement of metabolite production from this microalga. In this study, stress was introduced to the Chlorella sorokiniana culture to produce high-value metabolites such as carotenoids and phenolic content. The small RNA transcriptome of C. sorokiniana was sequenced, focusing on microRNA (miRNA) content. From the analysis, 98 miRNAs were identified in cultures subjected to normal and stress conditions. The functional analysis result showed that the miRNA targets found were most often involved in the biosynthesis of secondary metabolites, followed by protein metabolism, cell cycle, and porphyrin and chlorophyll metabolism. Furthermore, the biosynthesis of secondary metabolites such as carotenoids, terpenoids, and lipids was found mostly in stress conditions. These results may help to improve our understanding of regulatory mechanisms of miRNA in the biological and metabolic process of Chlorella species. It is important and timely to determine the true potential of this microalga species and to support the potential for genetic engineering of microalgae as they receive increasing focus for their development as an alternative source of biofuel, food, and health supplements.
Fulltext Major QTLs for Trunk Height and Correlated Agronomic Traits Provide Insights into Multiple Trait Integration in Oil Palm Breeding

Teh CK, Ong AL, Mayes S, Massawe F, Appleton DR

Genes (Basel), 2020 07 21;11(7).
PMID: 32708151 DOI: 10.3390/genes11070826

Superior oil yield is always the top priority of the oil palm industry. Short trunk height (THT) and compactness traits have become increasingly important to improve harvesting efficiency since the industry started to suffer yield losses due to labor shortages. Breeding populations with low THT and short frond length (FL) are actually available, such as Dumpy AVROS pisifera (DAV) and Gunung Melayu dura (GM). However, multiple trait stacking still remains a challenge for oil palm breeding, which usually requires 12-20 years to complete a breeding cycle. In this study, yield and height increment in the GM × GM (GM-3341) and the GM × DAV (GM-DAV-3461) crossing programs were evaluated and palms with good yield and smaller height increment were identified. In the GM-3341 family, non-linear THT growth between THT_2008 (seven years old) and THT_2014 (13 years old) was revealed by a moderate correlation, suggesting that inter-palm competition becomes increasingly important. In total, 19 quantitative trait loci (QTLs) for THT_2008 (8), oil per palm (O/P) (7) and FL (4) were localized on the GM-3341 linkage map, with an average mapping interval of 2.01 cM. Three major QTLs for THT_2008, O/P and FL are co-located on chromosome 11 and reflect the correlation of THT_2008 with O/P and FL. Multiple trait selection for high O/P and low THT (based on the cumulative effects of positive alleles per trait) identified one palm from 100 palms, but with a large starting population of 1000-1500 seedling per cross, this low frequency could be easily compensated for during breeding selection.
Fulltext Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia

Yik MY, Azlan A, Rajasegaran Y, Rosli A, Yusoff NM, Moses EJ

Genes (Basel), 2021 07 30;12(8).
PMID: 34440361 DOI: 10.3390/genes12081188

The proliferative capacity and continuous survival of cells are highly dependent on telomerase expression and the maintenance of telomere length. For this reason, elevated expression of telomerase has been identified in virtually all cancers, including leukemias; however, it should be noted that expression of telomerase is sometimes observed later in malignant development. This time point of activation is highly dependent on the type of leukemia and its causative factors. Many recent studies in this field have contributed to the elucidation of the mechanisms by which the various forms of leukemias increase telomerase activity. These include the dysregulation of telomerase reverse transcriptase (TERT) at various levels which include transcriptional, post-transcriptional, and post-translational stages. The pathways and biological molecules involved in these processes are also being deciphered with the advent of enabling technologies such as next-generation sequencing (NGS), ribonucleic acid sequencing (RNA-Seq), liquid chromatography-mass spectrometry (LCMS/MS), and many others. It has also been established that TERT possess diagnostic value as most adult cells do not express high levels of telomerase. Indeed, studies have shown that prognosis is not favorable in patients who have leukemias expressing high levels of telomerase. Recent research has indicated that targeting of this gene is able to control the survival of malignant cells and therefore offers a potential treatment for TERT-dependent leukemias. Here we review the mechanisms of hTERT regulation and deliberate their association in malignant states of leukemic cells. Further, we also cover the clinical implications of this gene including its use in diagnostic, prognostic, and therapeutic discoveries.
Fulltext Molecular Regulation of Lipogenesis, Adipogenesis and Fat Deposition in Chicken

Nematbakhsh S, Pei Pei C, Selamat J, Nordin N, Idris LH, Abdull Razis AF

Genes (Basel), 2021 03 13;12(3).
PMID: 33805667 DOI: 10.3390/genes12030414

In the poultry industry, excessive fat deposition is considered an undesirable factor, affecting feed efficiency, meat production cost, meat quality, and consumer's health. Efforts to reduce fat deposition in economically important animals, such as chicken, can be made through different strategies; including genetic selection, feeding strategies, housing, and environmental strategies, as well as hormone supplementation. Recent investigations at the molecular level have revealed the significant role of the transcriptional and post-transcriptional regulatory networks and their interaction on modulating fat metabolism in chickens. At the transcriptional level, different transcription factors are known to regulate the expression of lipogenic and adipogenic genes through various signaling pathways, affecting chicken fat metabolism. Alternatively, at the post-transcriptional level, the regulatory mechanism of microRNAs (miRNAs) on lipid metabolism and deposition has added a promising dimension to understand the structural and functional regulatory mechanism of lipid metabolism in chicken. Therefore, this review focuses on the progress made in unraveling the molecular function of genes, transcription factors, and more notably significant miRNAs responsible for regulating adipogenesis, lipogenesis, and fat deposition in chicken. Moreover, a better understanding of the molecular regulation of lipid metabolism will give researchers novel insights to use functional molecular markers, such as miRNAs, for selection against excessive fat deposition to improve chicken production efficiency and meat quality.
Fulltext Pathogenic Mitochondria DNA Mutations: Current Detection Tools and Interventions

Mustafa MF, Fakurazi S, Abdullah MA, Maniam S

Genes (Basel), 2020 02 12;11(2).
PMID: 32059522 DOI: 10.3390/genes11020192

Mitochondria are best known for their role in energy production, and they are the only mammalian organelles that contain their own genomes. The mitochondrial genome mutation rate is reported to be 10-17 times higher compared to nuclear genomes as a result of oxidative damage caused by reactive oxygen species during oxidative phosphorylation. Pathogenic mitochondrial DNA mutations result in mitochondrial DNA disorders, which are among the most common inherited human diseases. Interventions of mitochondrial DNA disorders involve either the transfer of viable isolated mitochondria to recipient cells or genetically modifying the mitochondrial genome to improve therapeutic outcome. This review outlines the common mitochondrial DNA disorders and the key advances in the past decade necessary to improve the current knowledge on mitochondrial disease intervention. Although it is now 31 years since the first description of patients with pathogenic mitochondrial DNA was reported, the treatment for mitochondrial disease is often inadequate and mostly palliative. Advancements in diagnostic technology improved the molecular diagnosis of previously unresolved cases, and they provide new insight into the pathogenesis and genetic changes in mitochondrial DNA diseases.
Fulltext Population Genomics of an Anadromous Hilsa Shad Tenualosa ilisha Species across Its Diverse Migratory Habitats: Discrimination by Fine-Scale Local Adaptation

Asaduzzaman M, Igarashi Y, Wahab MA, Nahiduzzaman M, Rahman MJ, Phillips MJ, et al.

Genes (Basel), 2019 12 30;11(1).
PMID: 31905942 DOI: 10.3390/genes11010046

The migration of anadromous fish in heterogenic environments unceasingly imposes a selective pressure that results in genetic variation for local adaptation. However, discrimination of anadromous fish populations by fine-scale local adaptation is challenging because of their high rate of gene flow, highly connected divergent population, and large population size. Recent advances in next-generation sequencing (NGS) have expanded the prospects of defining the weakly structured population of anadromous fish. Therefore, we used NGS-based restriction site-associated DNA (NextRAD) techniques on 300 individuals of an anadromous Hilsa shad (Tenualosa ilisha) species, collected from nine strategic habitats, across their diverse migratory habitats, which include sea, estuary, and different freshwater rivers. The NextRAD technique successfully identified 15,453 single nucleotide polymorphism (SNP) loci. Outlier tests using the FST OutFLANK and pcadapt approaches identified 74 and 449 SNPs (49 SNPs being common), respectively, as putative adaptive loci under a divergent selection process. Our results, based on the different cluster analyses of these putatively adaptive loci, suggested that local adaptation has divided the Hilsa shad population into two genetically structured clusters, in which marine and estuarine collection sites were dominated by individuals of one genetic cluster and different riverine collection sites were dominated by individuals of another genetic cluster. The phylogenetic analysis revealed that all the riverine populations of Hilsa shad were further subdivided into the north-western riverine (turbid freshwater) and the north-eastern riverine (clear freshwater) ecotypes. Among all of the putatively adaptive loci, only 36 loci were observed to be in the coding region, and the encoded genes might be associated with important biological functions related to the local adaptation of Hilsa shad. In summary, our study provides both neutral and adaptive contexts for the observed genetic divergence of Hilsa shad and, consequently, resolves the previous inconclusive findings on their population genetic structure across their diverse migratory habitats. Moreover, the study has clearly demonstrated that NextRAD sequencing is an innovative approach to explore how dispersal and local adaptation can shape genetic divergence of non-model anadromous fish that intersect diverse migratory habitats during their life-history stages.
Fulltext Sex Chromosome Turnover in Bent-Toed Geckos (Cyrtodactylus)

Keating SE, Blumer M, Grismer LL, Lin A, Nielsen SV, Thura MK, et al.

Genes (Basel), 2021 01 19;12(1).
PMID: 33477871 DOI: 10.3390/genes12010116

Lizards and snakes (squamates) are known for their varied sex determining systems, and gecko lizards are especially diverse, having evolved sex chromosomes independently multiple times. While sex chromosomes frequently turnover among gecko genera, intrageneric turnovers are known only from Gekko and Hemidactylus. Here, we used RADseq to identify sex-specific markers in two species of Burmese bent-toed geckos. We uncovered XX/XY sex chromosomes in Cyrtodactylus chaunghanakwaensis and ZZ/ZW sex chromosomes in Cyrtodactylus pharbaungensis. This is the third instance of intrageneric turnover of sex chromosomes in geckos. Additionally, Cyrtodactylus are closely related to another genus with intrageneric turnover, Hemidactylus. Together, these data suggest that sex chromosome turnover may be common in this clade, setting them apart as exceptionally diverse in a group already known for diverse sex determination systems.
Fulltext The Role of microRNAs in Alzheimer's Disease and Their Therapeutic Potentials

Miya Shaik M, Tamargo IA, Abubakar MB, Kamal MA, Greig NH, Gan SH

Genes (Basel), 2018 Mar 21;9(4).
PMID: 29561798 DOI: 10.3390/genes9040174

MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals with Alzheimer's disease (AD) as compared to those of healthy elderly adults. Some of the miRNAs found to be dysregulated in AD have been reported to correlate with neuropathological changes, including plaque and tangle accumulation, as well as altered expressions of species that are known to be involved in AD pathology. To examine the potentially pathogenic functions of several dysregulated miRNAs in AD, we review the current literature with a focus on the activities of ten miRNAs in biological pathways involved in AD pathogenesis. Comprehensive understandings of the expression profiles and activities of these miRNAs will illuminate their roles as potential therapeutic targets in AD brain and may lead to the discovery of breakthrough treatment strategies for AD.
Fulltext The Unique Biology behind the Early Onset of Breast Cancer

Siddig A, Tengku Din TADA, Mohd Nafi SN, Yahya MM, Sulong S, Wan Abdul Rahman WF

Genes (Basel), 2021 03 05;12(3).
PMID: 33807872 DOI: 10.3390/genes12030372

Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.
Fulltext The Use of Genetic and Gene Technologies in Shaping Modern Rapeseed Cultivars (Brassica napus L.)

Ton LB, Neik TX, Batley J

Genes (Basel), 2020 09 30;11(10).
PMID: 33008008 DOI: 10.3390/genes11101161

Since their domestication, Brassica oilseed species have undergone progressive transformation allied with the development of breeding and molecular technologies. The canola (Brassica napus) crop has rapidly expanded globally in the last 30 years with intensive innovations in canola varieties, providing for a wider range of markets apart from the food industry. The breeding efforts of B. napus, the main source of canola oil and canola meal, have been mainly focused on improving seed yield, oil quality, and meal quality along with disease resistance, abiotic stress tolerance, and herbicide resistance. The revolution in genetics and gene technologies, including genetic mapping, molecular markers, genomic tools, and gene technology, especially gene editing tools, has allowed an understanding of the complex genetic makeup and gene functions in the major bioprocesses of the Brassicales, especially Brassica oil crops. Here, we provide an overview on the contributions of these technologies in improving the major traits of B. napus and discuss their potential use to accomplish new improvement targets.
Fulltext Transcriptome Profiling of Haloxylon persicum (Bunge ex Boiss and Buhse) an Endangered Plant Species under PEG-Induced Drought Stress

Thayale Purayil F, Rajashekar B, S Kurup S, Cheruth AJ, Subramaniam S, Hassan Tawfik N, et al.

Genes (Basel), 2020 06 10;11(6).
PMID: 32531994 DOI: 10.3390/genes11060640

Haloxylon persicum is an endangered western Asiatic desert plant species, which survives under extreme environmental conditions. In this study, we focused on transcriptome analysis of H. persicum to understand the molecular mechanisms associated with drought tolerance. Two different periods of polyethylene glycol (PEG)-induced drought stress (48 h and 72 h) were imposed on H. persicum under in vitro conditions, which resulted in 18 million reads, subsequently assembled by de novo method with more than 8000 transcripts in each treatment. The N50 values were 1437, 1467, and 1524 for the control sample, 48 h samples, and 72 h samples, respectively. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis resulted in enrichment of mitogen-activated protein kinase (MAPK) and plant hormone signal transduction pathways under PEG-induced drought conditions. The differential gene expression analysis (DGEs) revealed significant changes in the expression pattern between the control and the treated samples. The KEGG analysis resulted in mapping transcripts with 138 different pathways reported in plants. The differential expression of drought-responsive transcription factors depicts the possible signaling cascades involved in drought tolerance. The present study provides greater insight into the fundamental transcriptome reprogramming of desert plants under drought.
Fulltext Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance-An Update

Chong PP, Chin VK, Wong WF, Madhavan P, Yong VC, Looi CY

Genes (Basel), 2018 Nov 07;9(11).
PMID: 30405082 DOI: 10.3390/genes9110540

Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.
Fulltext Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins

Juhari WKW, Ahmad Amin Noordin KB, Zakaria AD, Rahman WFWA, Mokhter WMMWM, Hassan MRA, et al.

Genes (Basel), 2021 09 20;12(9).
PMID: 34573430 DOI: 10.3390/genes12091448

BACKGROUND: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.
METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.
RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.
CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

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