Showing papers in "Journal of Genetics in 2021"
TL;DR: In this paper, the authors have identified some novel lead phytochemicals present in Azadirachta indica and Aloe barbadensis which could be utilized for further in vitro and in vivo anti-SARS-CoV-2 drug discovery.
Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is at present an emerging global public health crisis. Angiotensin converting enzyme 2 (ACE2) and trans-membrane protease serine 2 (TMPRSS2) are the two major host factors that contribute to the virulence of SARS-CoV-2 and pathogenesis of coronavirus disease-19 (COVID-19). Transmission of SARS-CoV-2 from animal to human is considered a rare event that necessarily requires strong evolutionary adaptations. Till date no other human cellular receptors are identified beside ACE2 for SARS-CoV-2 entry inside the human cell. Proteolytic cleavage of viral spike (S)-protein and ACE2 by TMPRSS2 began the entire host-pathogen interaction initiated with the physical binding of ACE2 to S-protein. SARS-CoV-2 S-protein binds to ACE2 with much higher affinity and stability than that of SARS-CoVs. Molecular interactions between ACE2-S and TMPRSS2-S are crucial and preciously mediated by specific residues. Structural stability, binding affinity and level of expression of these three interacting proteins are key susceptibility factors for COVID-19. Specific protein-protein interactions (PPI) are being identified that explains uniqueness of SARS-CoV-2 infection. Amino acid substitutions due to naturally occurring genetic polymorphisms potentially alter these PPIs and poses further clinical heterogeneity of COVID-19. Repurposing of several phytochemicals and approved drugs against ACE2, TMPRSS2 and S-protein have been proposed that could inhibit PPI between them. We have also identified some novel lead phytochemicals present in Azadirachta indica and Aloe barbadensis which could be utilized for further in vitro and in vivo anti-COVID-19 drug discovery. Uncovering details of ACE2-S and TMPRSS2-S interactions would further contribute to future research on COVID-19.
65 citations
TL;DR: The gene-for-gene relationship of host-pathogen interaction explained by H. Flor in mid-20th century set a milestone in understanding the biochemical and genetic basis of plant diseases and several components involved in plantpathogen interactions.
Abstract: The gene-for-gene relationship of host-pathogen interaction explained by H. H. Flor in mid of the 20th century set a milestone in understanding the biochemical and genetic basis of plant diseases and several components involved in plant-pathogen interactions. It highlighted the importance of accomplishing differential sets and understanding the pathogen population structure, it further led to the identification and cloning of several resistance (R) genes in plants. These R genes have been deployed and altered for fighting against diseases in a large number of crops using various conventional approaches and biotechnological tools. Identification of R genes and their corresponding Avr genes in many cases played a significant role in understanding of R-Avr gene interactions. Rapid cloning of R genes and editing of susceptible R genes are the other avenues that have broadened the horizon of utilizing R genes in crop improvement programmes. Further, combining R genes with quantitative disease resistance genes has paved the way to develop durable resistance in cultivars. The recent advances in genetics, genomics, bioinformatics and other OMICS tools are now providing greater prospects for deeper understanding of host-pathogen interaction.
17 citations
TL;DR: In this article, the authors discuss the key oncogenic miRNAs implicated in cell migration, invasion and metastasis, and angiogenesis, and summarize the evidence for their potential therapeutic uses in clinical practice.
Abstract: A growing body of evidence demonstrates that the oncogenic miRNAs are critical components that are involved in breast cancer (BC) progression. Thus, they are attracting a great deal of consideration as they provide opportunities for the novel avenues for developing BC targeted therapy. In the current review, we try to discuss the key oncogenic miRNAs implicated in cell migration, invasion and metastasis (e.g., miR-9, miR-10b, miR-10b-5p, miR-17/9, miR-21, miR-103/107, miR-181b-1, miR-301, miR-301a, miR-373, miR- 489, miR-495 and miR-520c), apoptosis inhibition (e.g., miR-21, miR-155, miR-181, miR-182 and miR-221/222), cell proliferation (e.g., miR-221/222, miR-17/92, miR-21, miR-301a, miR-155, miR-181 b, miR-182, miR-214, miR-20b, miR-29a, miR-196, miR-199a-3p, miR- 210, miR-301a, miR-375, miR-378-3p and miR-489), and angiogenesis (e.g., miR-9, miR-17/92 cluster, miR-93 and miR-210). In particular, here, we considered miRNA-based therapeutic approaches to summarize the evidence for their potential therapeutic uses in clinical practice. Therefore, miRNA mimics (i.e., replacement and restoration of miRNAs) and inhibition therapy (e.g., anti-miRNA oligonucleotides (AMO), antagomiRs or antisense oligonucleotides (ASOs): cholesterol-conjugated anti-miRs and locked nucleic acid (LNA)), miRNA sponges, nanoparticles (NPs), multiple-target anti-mirna antisense oligonucleotide technology (MTg-AMOs), and artificial miRNAs (amiRNAs) have been indicated throughout the article as much as possible.
17 citations
TL;DR: The current understanding of cricRNAs biogenesis, regulatory mechanisms, reviews of recent findings and circRNA as potential biomarker are presented.
Abstract: Circular RNAs (circRNAs) are a class of noncoding RNA molecules formed by the back splicing process. Compared to linear mRNA molecules they are more stable. CircRNA acts as miRNA sponges, regulates translation, epigenetic alterations, etc. However, the most significant aspect of circRNAs has been its role in regulating the hallmark of cancer and diabetes mellitus. Several circRNAs are extensively expressed in individuals with cancer and diabetics. Dysregulated expression of various circRNAs plays a crucial part in the development of type 2 diabetes mellitus. In the present review, we present the current understanding of cricRNAs biogenesis, regulatory mechanisms, reviews of recent findings and circRNA as potential biomarker.
11 citations
TL;DR: The article summarizes the protocol, uses, bioinformatics tools, its application, and future prospects of skim sequencing in crop improvement programmes with a view to increasing the application of skims sequencing-based genotyping.
Abstract: High-throughput genotyping has become more convenient and cost-effective due to recent advancements in next-generation sequencing (NGS) techniques. Numerous approaches exploring sequencing advances for genotyping have been developed over the past decade, which includes different variants of genotyping-by-sequencing (GBS), and restriction-site associated DNA sequencing (RAD-seq). Most of these methods are based on the reduced representation of the genome, which ultimately reduces the cost of sequencing by many folds. However, continuously lowering the cost of sequencing makes it more convenient to use whole genome-based approaches. In this regard, skim sequencing, where low coverage whole-genome sequencing is used for the identification of large numbers of polymorphic markers cost-effectively. In the present review, we have discussed recent technological advancements, applicability, and challenges of skim sequencing-based genotypic approaches for crop improvement programmes. Skim sequencing is being extensively used for genotyping in diverse plant species and has a wide range of applications, particularly in quantitative trait loci (QTL) mapping, genomewide association studies (GWAS), fine genetic map construction, and identification of recombination and gene conversion events in various breeding programmes. The cost-effectiveness, simplicity, and genomewide coverage will increase the application of skims sequencing-based genotyping. The article summarizes the protocol, uses, bioinformatics tools, its application, and future prospects of skim sequencing in crop improvement.
9 citations
TL;DR: In this paper, the authors discuss the known mechanisms associated with X-chromosome inactivation, when and how does it initiate, spreads and maintain, as well as the mechanisms that allow some genes to escape from it.
Abstract: X-chromosome inactivation (XCI) is a process involved in the pathogenesis of several diseases. In this mini review, we discuss the known mechanisms associated with XCI, when and how does it initiate, spreads and maintain, as well as the mechanisms that allow some genes to escape from it. We address the skewed XCI, condition in which the process are not fully randomized and its consequences to the phenotype of some pathologies. We debate about the known pathologies implicated, including X unbalanced rearrangements, X-autosomal balanced translocations, Turner and Klinefelter syndromes and also for X-linked diseases and its consequences in males and females. Some pathologies are discussed more in detail such as intellectual disability with a recognized relationship with XCI. Finally, possible future implications of genomic therapy and treatment of patients and list of areas that need further research on this topic are addressed.
8 citations
TL;DR: In this article, the authors used HE staining, immunofluorescence staining and TUNEL staining to observe the gross and histopathology of testis in homozygous and wild rats.
Abstract: Knockout Dnah17 rats were generated due to its potential involvement in myopia. Subsequent study suggested that the homozygous truncation variants in DNAH17 is associated with male fertility but not myopia. Sperm count and sperm motility were measured in male rats. HE staining, immunofluorescence staining and TUNEL staining were used to observe the gross and histopathology of testis in homozygous and wild rats. Dnah17 knockout rats were generated by CRISPR/Cas9 gene editing. In the process of breeding rats, homozygous male rats were noted to be infertile, with significantly decreased number of sperm suggesting cryptozoospermia that was further confirmed by histologic studies. TUNEL assay showed an increased apoptosis in homozygous testes compared with wild type (P<0.001). A significant reduction of spermatocytes was observed in homozygotes compared with wild type (P=0.025) by immunofluorescence. These results suggest that DNAH17 is critical for spermatogenesis in male rats.
7 citations
TL;DR: The marker information generated here is novel and of paramount importance for future genetic studies in D. falcatum as well as other temperate bamboo species through cross-transferability.
Abstract: Drepanostachyum falcatum (Nees) Keng f. is one of the most widely distributed shrubby bamboo species in the temperate region of northwest (NW) Himalayas. Along with the other three temperate bamboo species, namely Yushania anceps, Thamnocalamus spathiflorus and Himalayacalamus falconeri, commonly called as 'ringal', and utilized for making various articles of household and commercial purpose by local artisans. Despite huge ecological and socio-economic importance, they are least studied and lacks baseline genetic information. In this study, ~10 Gb genome sequence data with 70.68 million reads were generated for D. falcatum, through genome skimming approach based on high throughput next-generation sequencing technology with Illumina protocol. The high-quality reads were de novo assembled into 31,997 contigs, which comprised 1943 microsatellite repeats. The dinucleotide and trinucleotide repeats were most abundantly distributed in the genome with 52.95 and 41.17%, respectively. Depending on the sufficient flanking sequence, only 1123 repeats were successfully tagged with primer pairs and these sites were designated as sequence-tagged microsatellite (STMS) markers. Further, a subset of 106 STMS markers were validated through PCR amplification; 77 marker loci were successfully amplified, and 48 of these showed polymorphism. Same set of marker loci were also tested for their cross-amplification in other three temperate bamboo species of the NW Himalayas, which revealed good level of transferability (27-48%) but lesser polymorphism (4-12%). In addition, the genomewide in silico cross-amplification revealed poor cross-transferability in other bamboo taxa representing four different phylogenetic lineages, namely Phyllostachys edulis (10.2%), Bonia amplexicaulis (3.03%), Guadua angustifolia (1.60%), Olyra latifolia (0.89%) and Raddia guianensis (0.36%). Ten polymorphic markers were further used to estimate the measures of genetic diversity in two natural populations, which revealed high genetic diversity (polymorphic information content, PIC = 0.889; expected heterozygosity, He = 0.756) and low genetic differentiation (FST=0.061; Nm = 5.445). To the best of our knowledge, this is one of the pioneer studies carried out for the development of genomic STMS markers through genome skimming approach in Indian bamboo species. The marker information generated here is novel and of paramount importance for future genetic studies in D. falcatum as well as other temperate bamboo species through cross-transferability.
5 citations
TL;DR: In this article, the codon usage bias (CUB) and the intraspecific genetic divergence of three Asian Jatropha curcas genomes were analyzed, and the factors shaping CUB were identified in all three genomes of J. curcas.
Abstract: Jatropha curcas has recently emerged as an important bioenergy plant which is an ideal alternative for fossil fuels. It is particularly significant to analyse the codon usage bias (CUB) and further evaluate the intraspecific genetic divergence of three J. curcas in Asia, considering its potential economic benefits and various utilities. In the present study, the patterns of CUB were systematically compared, and the factors shaping CUB were identified in all three genomes of J. curcas. Our observations indicate that the preference for A/T nucleotides and A/T ending codons was present in all the three genomes. Moreover, 11 identical high-frequency codons as well as the optimal expression receptor Nicotiana tabacum were confirmed. Besides, it was observed that CUB resulted from the combined effects of natural selection and mutation pressure, while the natural selection was the determining factor. Eventually, similarity indices based on relative synonymous codon usage (RSCU) values implied low intraspecific genetic divergence in three Asian J. curcas. This study provides useful clues for improving the expression level of exogenous genes and optimizing breeding programmes by molecular-assisted breeding in J. curcas.
5 citations
TL;DR: In this paper, the authors reported the first case with HADDTS in the Middle-Eastern population and deployed whole-exome sequencing was deployed to identify the variant(s) causing this condition.
Abstract: Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (HADDTS) is an extremely rare autosomal dominant genetic disease caused by disruptive pathogenic variants in CTBP1. There are merely 12 cases reported to have pathogenic variants in the CTBP1 gene. Here, we report the first case with HADDTS in the Middle-Eastern population. In the present study, whole-exome sequencing was deployed to identify the variant(s) causing this condition. Subsequently, Sanger sequencing was performed to confirm the variant. The clinical evaluation of the patient is written according to the thoroughly carried out examinations and clinical investigations. A novel single frameshift pathogenic variant in CTBP1 (NM_001328.3:c.1315_1316delCA, p.Gln439ValfsTer84) was identified as the cause for HADDTS in the proband. Our findings enhance the knowledge of poorly studied CTBP1. The newly reported patient is phenotypically different in comparison to the previously reported cases. He has no sign of hypotonia, difficulty in walking or standing.
5 citations
TL;DR: In this paper, the expression of sucrose and starch metabolism genes was studied in leaves of cold-sensitive (GPF2) and cold-tolerant (ICC 16349) chickpea genotypes.
Abstract: Low temperature (LT) causes significant yield losses in chickpea (Cicer arietinum L.). The sucrose starch metabolism is associated with abiotic-stress tolerance or sensitivity in plants. The changes in sugars and starch contents under LT in chickpea have already been studied, however, no information is available on LT-induced alterations in transcription of carbohydrate metabolic pathway genes in chickpea. To understand the differences in the regulation of sucrose and starch metabolism under LT, the expression of sucrose and starch metabolism genes was studied in leaves of cold-sensitive (GPF2) and cold-tolerant (ICC 16349) chickpea genotypes. The mRNA sequences of chickpea genes were retrieved from the public databases followed by confirmation of identity and characterization. All the genes were functional in chickpea. Between the two paralogues of cell wall invertase, cell wall invertase 3×2 (CWINx2) was the truncated version of cell wall invertase 3×1 (CWINx1) with the loss of 241 bases in the mRNA and 67 amino acids at N terminal of the protein. Comparison of expression of the genes between control (22°C day / 16°C night) and LT treated (4°C; 72 h) plants revealed that granule bound starch synthase 2 (GBSS2) and β-amylase 3 (BAM3) were upregulated in ICC 16349 whereas sucrose phosphate synthase 2 (SPS2), CWINx1, CWINx2 and β-amylase 1 (BAM1) were downregulated. In contrast to this, SPS2, CWINx1, CWINx2 and BAM1 were upregulated and GBSS2 downregulated in GPF2 under LT. The gene expression data suggested that UGPase, CWINs, GBSS2 and BAM3 are important components of cold-tolerance machinery of chickpea.
TL;DR: In this article, a collection of 182 diverse chickpea genotypes was assessed for genetic variation in 15 traits including phenological, physiological and yield-related traits under both normal sown (NS) and late-sown (LS) conditions for two years 2017-2018 and 2018-2019, which revealed significant variation for all the traits.
Abstract: High temperature (HT) stress is assuming serious production constraint for chickpea production worldwide. A collection of 182 diverse chickpea genotypes was assessed for genetic variation in 15 traits including phenological, physiological and yield-related traits under both normal sown (NS) and late sown (LS) conditions for two years 2017–2018 and 2018–2019, which revealed significant variation for all the traits. Association mapping of chickpea genotypes was also conducted with 120 simple sequence repeat markers distributed across all the chickpea chromosomes to discern the molecular diversity and to capture the significant marker-trait association (MTA). MTA analysis based on mixed linear model (MLM) revealed a total of 24 and 14 significant associations for various traits evaluated under NS conditions in 2017 and 2018, respectively. Similarly, a total of 17 and 34 significant associations for various traits were also recorded under LS conditions in 2018 and 2019, respectively. Notably, ICCM0297, NCPGR150, TAA160 and NCPGR156 markers showed significant MTA under both NS and LS conditions and GA11 exhibited significant MTA for filled pod% under late sown condition for both years. Thus, these markers could be useful for genomics-assisted breeding for developing heat-tolerant chickpea genotype.
TL;DR: In this paper, the authors investigated the genetics controlling coconut juice-like fragrance in inflorescence of sorghum cultivar ‘Ambemohor’ and found that BADH1 is a candidate gene for the coconut juicelike fragrance.
Abstract: Aroma is an important trait that can enhance the product value in several crops. Pandan-like fragrance resulting from accumulation of 2-acetyl-1-pyrroline (2AP) is one of the pleasant aromas in food crops which is caused by null or missense mutations in betaine aldehyde dehydrogenase 2 (BADH2) gene. In addition, betaine aldehyde aehydrogenase 1 (BADH1) has shown to be associated with aroma in rice. In this study, we investigated the genetics controlling coconut juice-like fragrance in inflorescence of sorghum cultivar ‘Ambemohor’. 2AP analysis in seeds revealed that Ambemohor possessed no 2AP. An F2 population developed from the cross between Ambemohor × KU630 (nonfragrant) segregated into a ratio of 3 (fragrant) : 1 (nonfragrant), suggesting that the coconut juice-like fragrance in Ambemohor is controlled by a single dominant gene, designated ‘Aro’. Bulked segregant analysis suggested that the gene controlling fragrance in Ambemohor is located on sorghum chromosome 6. Quantitative trait locus (QTL) analysis identified a major QTL, qAro6.1, for the fragrance located on chromosome 6 between markers SB3567 and SB3570. Bioinformatics analysis revealed that SB3567 and SB3570 were 217.8 kb apart and there were 29 annotated genes in this region including BADH1. Sequence analysis revealed that BADH1 sequences in Ambemohor and KU630 differed in size, but their coding sequences (CDS) were of same size. CDS alignment revealed four single-nucleotide polymorphisms (SNPs) between Ambemohor and KU630 in which two SNPs caused amino change in BADH1 of Ambemohor. These results suggested that BADH1 is a candidate gene for the coconut juice-like fragrance in Ambemohor.
TL;DR: In this article, a mungbean yellow mosaic India virus (MYMIV)-resistant association mapping panel was constructed to minimize the effect of yellow mosaic disease on crop performance, which was performed with 290 diverse Vigna accessions including wild and cultivated accessions.
Abstract: Mungbean (Vigna radiata L. Wilczek) is one of the most important warm season food legumes which contributes significantly towards nutritional security and environmental sustainability. Marker-trait association (MTA) for agronomic characters offer opportunities to deploy marker-assisted breeding for genetic amelioration of crops. This investigation was carried out with an objective to decipher population genetic structure of diverse Vigna accessions and detect microsatellite loci linked to major agronomic traits for mungbean improvement. The study was initiated with 290 diverse Vigna accessions including wild and cultivated accessions. A mungbean yellow mosaic India virus (MYMIV)-resistant association mapping panel was constructed to minimize the effect of yellow mosaic disease on crop performance. Among these, 117 accessions including 55 cultivated and 63 wild accessions were found highly resistant to MYMIV. After multi-environment phenotyping, a panel of 70 MYMIV-resistant mungbean accessions was subjected to analysis for assessing the population genetic structure as well as MTA for important agronomic traits. There was sufficient genetic variation among the 70-mungbean genotypes as depicted by 91 microsatellite markers. Population genetic structure analysis grouped the genotypes into five subpopulations. The locus GMES0162 (LG4) was strongly associated with days to first flowering, whereas loci CEDG 035 (LG8), DMB SSR001 (LG6), DMB SSR008 (LG4) and CEDG 168 (LG11) were associated with pod number. These marker-trait associations will be helpful in genetic improvement of mungbean through molecular breeding.
TL;DR: In this paper, the authors used genetic variance components and type of gene action controlling yield and its component traits using six populations (P1, P2, F1, F 1, F2, BC1 and BC2) of the three bread wheat crosses.
Abstract: Grain yield is a complex polygenic trait representing a multiplicative end product of contributing yield attributes governed by simple to complex gene interactions. Deciphering the genetics and inheritance of traits/genes influencing yield is a prerequisite to harness the yield potential in any crop species. The objective of the present investigation was to estimate genetic variance components and type of gene action controlling yield and its component traits using six populations (P1, P2, F1, F2, BC1 and BC2) of the three bread wheat crosses. Cross I (25th HRWSN 2105 × WH 1080), cross II (22ndSAWYT323 × RSP 561) and cross III (22ndSAWYT333 × WH 1080) involving elite stripe rust resistant wheat genetic stocks in combination with commercial check varieties were used for analysis. A combination of morpho-physiological, biochemical and disease influencing traits were evaluated, thus exploring the possibility of multi-trait integration in future. Results revealed that the estimated mean effects (m) were highly significant for all the traits in all crosses, indicating that selected traits were quantitatively inherited. The estimate of dominant gene effect was highly significant for plant height, number of tillers per plant in all the three crosses. Grain yield per plant was highly significant in the cross II while total protein content was highly significant in both crosses II and III. Glycine betaine content showed significant additive genes effect. Duplicate epistasis was the most significant for traits like plant height, total protein content and grain yield per plant. Dominance gene effect was more important than additive gene effects in the inheritance of grain yield and most other traits studied. The magnitude of additive × additive gene effects was high and positively significant whereas dominance × dominance was negatively significant for most of the traits studied in the three crosses. Additive × dominance gene effects was of minor significance, thus indicating that selection for grain yield and its components should be delayed to later generations of breeding.
TL;DR: In this paper, it was observed that in many nonconsanguineous families with rare autosomal disorders, maternally and paternally inherited mutations are same, indicating common ancestor.
Abstract: India has a large heterogeneous population with its unique social and genetic characteristics. Tradition of marriage between specific caste groups have produced unique characteristics to the mutation spectrum of genetic disorders and may be a higher prevalence of autosomal recessive (AR) disorders in some communities. We observed that in many nonconsanguineous families with rare autosomal disorders, maternally and paternally inherited mutations are same, indicating common ancestor. In this era of genomic techniques, finding homozygous regions have become easy. It was seen that the patients with AR disorders, who were homozygous for the disease causing pathogenic / likely pathogenic variations, have large stretches (0.6-188 Mb) of homozygosity around the causative sequence variations. SNP microarray data of patients from consanguineous and nonconsanguineous families also showed that even patients from nonconsanguineous families had 3-49 Mb size regions of homozygosity. Long stretches of homozygosity around homozygous rare pathogenic variants in nonconsanguineous families with rare AR disorders supports the notion that these couples may have a common ancestor for more than six generations and the system of marriages between same groups. Hence, using the strategy of homozygosity by descent even in nonconsanguineous families can be fruitful in identifying the novel pathogenic variations and novel genes.
TL;DR: In this article, the authors investigated the population genetic variation of the serotonin transporter gene (SLC6A4), focussing on the single nucleotide polymorphisms (SNPs) and found that these SNPs were under strong selection pressure especially among East Asian populations with significantly high positive cross-population extended haplotype homozygosity scores compared to Africans.
Abstract: The serotonin transporter 5-HTT is encoded by a single gene SLC6A4. Polymorphisms in SLC6A4 has been associated with a wide variety of neurological and psychiatric disorders including increased risk of posttraumatic stress disorder, higher likelihood for depression, obsessive-compulsive disorder (OCD), increased hostility and criminal behaviour. Genes associated with complex diseases often exhibit strong signatures of purifying selection compared to others. Further, discernible population specific variation in the signature of natural selection have been observed for several complex disease-related genes. In this project we aimed to investigate the population genetic variation of the serotonin transporter gene (SLC6A4), focussing on the single nucleotide polymorphisms (SNPs). To this end, we employed 2504 individuals around the globe available in 1000 Genome project Phase III data and classified them into five ethnic groups: Americans (AMR), Europeans (EUR), Africans (AFR), East Asians (EAS) and South Asians (SAS). Principal component analysis (PCA) performed on all annotated SNPs of SLC6A4 depicted clear clustering between Africans and the rest of the world along PC1, and East Asians and other non-African populations along PC2. Further, these SNPs were found to be under strong selection pressure especially among East Asian populations with significantly high positive cross-population extended haplotype homozygosity scores compared to Africans, indicating that SLC6A4 has likely undergone a strong selective sweep among the East Asians in the recent past. Our study can potentially explain the association between polymorphisms in SLC6A4, and major depression and suicidal tendencies among people of East Asian ancestry and the absence of such associations among people of European ancestry.
TL;DR: A meta-analysis showed that Taq1A (allelic model: OR 0.856, 95% CI, 0.734-0.834) has a protective effect against the development of schizophrenia.
Abstract: Genetic factors play an important role in the pathogenesis of schizophrenia. Dysregulations in the dopaminergic system have long been known to play an influential role in the development of this disorder. Although a large number of studies have investigated the association between genetic polymorphisms in the genes involved in this system and the risk of schizophrenia, the results have been inconsistent. In this meta-analysis, we searched for publications in Ovid Medline, Embase, Web of Science (science citation index expanded), and PsycNET for articles published until January 2020. We identified case–control studies investigating the association between four common genetic polymorphisms (rs6277, rs1799732, rs1800497, and rs1801028) and the risk of schizophrenia. The studies were subsequently selected according to the predefined inclusion and exclusion criteria. The data extraction was conducted according to the PRISMA guidelines. We also assessed the quality of the studies and investigated publication bias using funnel plot and Egger’s regression test. The association analysis was conducted in allelic, dominant, and recessive genetic models. Subsequently, bioinformatics analysis of the effect of the polymorphisms found to be significantly associated with schizophrenia on protein stability, posttranslational modifications, and 3D protein structure was conducted. This meta-analysis showed that Taq1A (allelic model: OR, 0.856, 95% CI, 0.734–0.998) has a protective effect against the development of schizophrenia. Further, it was found that this variant may decrease ANKK1 protein stability. Further, this polymorphism was found to lead to the gain of modifications sites for ubiquitination (Ubi. score = −1.894) and methylation (Meth. score = −0.834). Several genetic factors contribute to the susceptibility of schizophrenia. The updated knowledge emerging from this meta-analysis showing the protective effect of rs1800497 polymorphism (Taq1A) can shed light on the role of Taq1A polymorphism in the susceptibility to schizophrenia and also pave way for further functional studies investigating the role of ANKK1 protein in the pathogenesis of schizophrenia.
TL;DR: These promising genotypes for a short duration with good yield have been selected and can be used for various chickpea breeding programmes to develop high yielding varieties in central India.
Abstract: Chickpea (Cicer arietinum L.) is an important food legume crop grown in arid and semi-arid regions of the world. In India, kabuli chickpea is grown in central India in ~0.5 million ha, predominantly under short winter (<110 days). Efforts are underway to select promising genotypes at the Food Legume Research Platform (FLRP), Amlaha, located in intensive kabuli chickpea growing area of India. Sixty-four kabuli chickpea lines were evaluated for agronomic traits during 2017-2018 and 2018-2019 crop seasons at FLRP following simple 8 X 8 lattice design with two replications. The analysis of variance over two years revealed significant variation exists for days to flowering, plant height, maturity period, biomass, seed size and seed yield. It was observed that with similar maturity time (106 days), FLIP09-432C produced 2273 kg/ha, which out-yielded the popular variety in central India, JGK-3 by 15%. The breeding lines, FLIP09- 436C, FLIP09-171C, FLIP09-373C and FLIP09-247C were also found promising for earliness (104-110 days), and high yielding with the good yield ability (1003-2273 kg/ha). These promising genotypes for a short duration with good yield have been selected and can be used for various chickpea breeding programmes to develop high yielding varieties in central India.
TL;DR: In this paper, the authors explored the correlation between polymorphisms in the preproinsulin gene and growth traits in grass carp and found that the H5 diplotype was significantly superior to the other diplotypes (P < 0.05) concerning body weight, body length, body height and body width, and its fatness was lower than those of the other dplotypes.
Abstract: The preproinsulin gene encodes a precursor protein of insulin, which is the most important hormone for lowering blood glucose levels and promoting the synthesis of glycogen, fat and protein. To explore the correlation between polymorphisms in the preproinsulin gene and growth traits in grass carp, the preproinsulin gene sequence, measuring a total of 5708 bp, was identified in the grass carp genome. The sequence includes a promoter, two introns and three exons, and encodes a 108-aa protein. A total of three SNPs were identified, including SNP1 (g.-2661C>G) in the promoter and SNP2 (g.1305G>C) and SNP3 (g.1682G>A) in intron 2. The correlation between SNPs and growth traits in grass carp was analysed by a general linear model (GLM). The results indicated that no genotype in each single SNP, SNP1 with SNP2, or SNP1 with SNP3 was related to rapid growth and low fatness, respectively. While eight genotypes of SNP1, SNP2 and SNP3 were combined into six types of effective diplotypes, the H5 diplotype was significantly superior to the other diplotypes (P<0.05) concerning body weight, body length, body height and body width, and its fatness was lower than those of the other diplotypes, except for H6 diplotype. This result indicated that the H5 diplotype of the preproinsulin gene in grass carp may be a candidate molecular marker for selecting fast-growing and low-fatness grass carp.
TL;DR: Findings suggest that variations in the EZH2 gene may have strong clinical significance as they can be targeted for prognosis, prevention and in drug development.
Abstract: EZH2 is a classic histone methyltransferase that causes the trimethylation of H3K27 and consequently suppresses the cancer preventive genes. The role of elevated levels of EZH2 expression in breast cancer aggressiveness and poor prognosis is very well established. The present study focusses on the insight of the clinically important SNPs of EZH2 gene in determining the structure-function relationship towards breast cancer susceptibility. For this purpose the EZH2 SNPs (rs41277434A>C and rs201135441C>T (A490T)) were computationally explored and further the prediction outcomes were validated by performing population-based association and pharmacogenetic study in north Indian region of Punjab. The results of the present analysis provided the novel insight of rs201135441C>T (A490T) mutation, that A>T change i.e. nonpolar amino acid to polar amino acid stabilizes the enzyme-substrate (EZH2-Histone) complex which in turn promotes trimethylation over histone 3 (H3) at lysine residue 27 (H3K27me3) and this might be leading to the methylation of the promoter region of various cancer preventive genes, hence may increase the risk of breast cancer susceptibility. Further the association based study of SNP rs201135441C>T (A490T) support the in silico outcomes by revealing that the T mutant allele of rs201135441 has significantly increased the risk of breast cancer susceptibility and also reduce the overall survival and progression free survival of ER+/tamoxifen treated breast cancer patients and triple negative breast cancer (TNBC) patients, respectively. To the best of our knowledge, this is the first study on EZH2 polymorphism with breast cancer. In conclusion, these findings suggest that these variations in the EZH2 gene may have strong clinical significance as they can be targeted for prognosis, prevention and in drug development.
TL;DR: The faba bean genotypes showed resistance to the disease scoring (0-9) with high yield as compared to the checks, Giza and Gwalior local, and can be utilized in faba Bean breeding programmes for the development of disease tolerant cultivars with highield.
Abstract: Faba bean (Vicia faba L.) is one of the earliest domesticated food legumes after chickpea and pea in the world. It is been produced in many countries including China, Ethiopia, Egypt, northern Europe, the Mediterranean region, central Asia, East Asia, Latin America and as a minor crop in India. The crop is affected by many diseases and alternaria leaf blight (Alternaria spp.) is one of the serious threat to faba bean production. Twenty-five lines of faba bean were selected from three international nurseries and were evaluated at ICARDA-FLRP-Amlaha during 2016-2017 and 2017-2018, to identify resistant lines against alternaria blight disease. A wide range of variation to disease reaction was observed among faba bean genotypes. One faba bean line (S2011-134) found tolerant, six genotypes (S2011-116, FLIP15-139, FLIP15-156, FLIP15-159, FLIP15-164-S2 and FLIP15-169) were found moderately tolerant and 16 genotypes were found susceptible to alternaria blight. The faba bean genotypes showed resistance to the disease scoring (0-9) with high yield as compared to the checks, Giza and Gwalior local. The identified sources of resistance can be utilized in faba bean breeding programmes for the development of disease tolerant cultivars with high yield.
TL;DR: The full-length sequence of birch-leaf pear is reported here, which can be used for breeding enhanced varieties and suggest candidate genes for molecular breeding.
Abstract: Drought limits the pear yield and quality. The birch-leaf pear (Pyrus betulifolia Bunge) is one of the most frequently used pear rootstocks. Identifying genes involved in drought resistance of P. betulifolia would suggest candidate genes for molecular breeding. We used single-molecule long-read sequencing technology to investigate the transcriptome of birch-leaf pear under drought stress. As a result, 362,139 consensus reads were identified using six databases, among which 342,162 genes were functionally annotated. Further, we identified 7094 long noncoding RNAs. The sequencing data contained 9891 alternative splicing and 100,836 alternative polyadenylation events. We report here the full-length sequence of birch-leaf pear, which can be used for breeding enhanced varieties.
TL;DR: Recent developments like designing of artificial transcription factors, nanotechnology- based transcriptional tools and CRISPR-based transcription modules with capabilities of precise regulation of gene expression patterns hold huge potentials in the field of transcriptional therapeutics.
Abstract: Transcription factors play very important role in cell fate determination. There are many cell specific transcription factors which when expressed ectopically may lead to cell fate conversion or transdifferentiation. Many of these transcription factors function differently based on their levels and stoichiometry. Many different types of differentiated cells have been generated from other differentiated cell types by expressing different levels and stoichiometry of reprogramming factors. Many methodologies have been developed for efficient cell fate conversion by regulating the levels and stoichiometry of transcription factors in a particular cocktail that have therapeutic values. An approach called phenotypic activation which involves overexpression of putative transcription factors has been developed as a tool to discover new transcription factors and their targets. Transcription factor overexpression may also have toxic effects where nonspecific electrostatic interactions and 'squelching' may lead to inhibition of many genes. Altered levels of transcription factors may have disastrous consequences like cancer. Recent developments like designing of artificial transcription factors, nanotechnology-based transcriptional tools and CRISPR-based transcription modules with capabilities of precise regulation of gene expression patterns hold huge potentials in the field of transcriptional therapeutics.
TL;DR: In this paper, seven Indian natural populations of D. bipectinata, two from north and five from south India, have been studied for their chromosomal inversion polymorphism.
Abstract: Genetic differentiation among different natural populations of a species depends upon the environmental factors and the evolutionary forces that operate on them. In this study, seven Indian natural populations of D. bipectinata, two from north and five from south India, have been studied for their chromosomal inversion polymorphism. A total of nine paracentric autosomal inversions were recorded from these seven places but only three of them, present on the 2L, 2R and 3L were found to be cosmopolitan in distribution. In all the populations, the frequency of standard gene arrangement was found to be high than their respective cosmopolitan inversion gene arrangement. The average heterozygosity (Ho) of cosmopolitan inversions increases from north to south. There is a latitudinal cline in the distribution of three cosmopolitan inversion arrangements because their frequency increases with the decreasing latitude, i.e. from north to south India. A comparison of the genetic profile of two north Indian and five south Indian natural populations of D. bipectinata reveals the role of natural selection as well as bottleneck effect in the genetic structuring of these populations which may be due to their varying ecological conditions to which they are constantly encountered. Further, the presence of all kinds of paracentric inversions in individual populations was analysed following Poisson distribution to see whether these inversions occur randomly in natural populations or not and the results indicate that north Indian populations show the random occurrence of these inversions than the populations derived from the south.
TL;DR: In this article, the authors analyzed worldwide population differentiation at the genomewide association study (GWAS)-significant UF-associated loci to test a hypothesis that population structure at risk loci might underlie the observed interethnic disparities in the prevalence.
Abstract: Uterine fibroids (UF) are a significant health problem bearing a substantial economic burden. The prevalence of the disease is disparate in populations of different ethnic ancestry being the highest in Africans. This study analysed worldwide population differentiation at the genomewide association study (GWAS)-significant UF-associated loci to test a hypothesis that population structure at risk loci might underlie the observed interethnic disparities in the prevalence. In total, 28 single-nucleotide polymorphism (SNP) with the GWAS significance for European Caucasians were analysed in female cohorts of the European, admixed American, African, east Asian, and South Asian populations retrieved from the 1000 Genomes Project data. Common population genetic structure estimators, polygenic risk score (unweighted and weighted) were computed. According to the Fisher's exact test, the populations were significantly differentiated (P<< 10-5) at the UF risk loci. The polygenic risk scores did not differ significantly when calculated across all loci. However, they differed when only loci with risk alleles showing the enrichment/depletion patterns correlating with the documented ethnicity-specific risk of the disease were included in the calculation. The population genetic structure at the UF risk loci is apparently a significant factor underlying the observed between-ethnic disparities in the disease prevalence.
TL;DR: In this article, the effect of APOE-e4 genotype on the logical memory delayed recall total (LDELTOTAL) score in late-onset Alzheimer disease (AD) was investigated.
Abstract: No study has focussed on the longitudinal effect of APOE-e4 genotype on the logical memory delayed recall total (LDELTOTAL) score in late-onset Alzheimer’s disease (AD). The LDELTOTAL scores were collected at baseline, 12, 24, 36 and 48 months from 382 participants with AD, 503 with cognitive normal (CN), 1293 with mild cognitive impairment (MCI) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). A linear mixed model (LMM) was used to investigate the effect of APOE-e4 on the longitudinal changes in the LDELTOTAL scores adjusted for age, gender, education and baseline Mini Mental State Examination score. There were significant differences in LDELTOTAL scores among AD, CN, and MCI (P < 0.0001) and among APOE-e4 alleles at baseline (P < 0.0001). In the multivariable LMM, elders with 75+ years (P = 0.0051), females (P < 0.0001), lower education (P < 0.0001), AD and MCI (both P values < 0.0001) were associated with decreased LDELTOTAL values, while the individuals with 1 or 2 APOE-e4 allele revealed significantly lower LDELTOTAL scores (both P values <0.0001) compared with individuals without APOE-e4 allele. Further, APOE-e4 alleles had significant interactions with four follow-up visits, where all follow-up visits showed significantly higher LDELTOTAL score. In addition, gender showed interaction with age, education and APOE-e4 with follow-up visits. Our findings provide the first evidence of the effect of APOE-e4 genotype on the logical memory declines related to AD. Further, APOE-e4 alleles showed interactions with gender and follow-up visits.
TL;DR: In this article, a resistant tetraploid nonprogenitors of wheat Aegilops triuncialis (UtUtCtCt) acc pau 3462 was crossed and backcrossed susceptible cultivar WL711(NN) by inducing homeologous pairing using CS ph1.
Abstract: The growing and cultivating resistant wheat crop varieties is important to meet the demands of the growing population and minimizing the yield losses due to foliar diseases. More important is the identification of novel resistance sources and transfer of resistance in ready to use form. In the current study, leaf rust (LR) and stripe rust (YR) resistant tetraploid nonprogenitors of wheat Aegilops triuncialis (UtUtCtCt) acc pau 3462 was crossed and backcrossed susceptible cultivar WL711(NN) by inducing homeologous pairing using CS ph1. Recurrent parent type plants were selected in subsequent generation with resistance to LR and YR and BC2F7 introgression line (2n=42) named ILtri have been developed. To understand the nature and inheritance of LR and YR resistance genes and to map their genomic location, F2 and F2:3 mapping populations were developed by crossing ILtri with WL711(NN). In F2 and F2:3, the seedlings and adult plants segregated into 3R:1S and 1HR:2Seg:1HS ratios, respectively for both LR and YR, indicating inheritance of single dominant all stage resistance gene working against both the rusts. These genes were temporary designated as Lrtri and Yrtri and were inherited independently.Molecular mapping of 614 SSR markers mapped the Lrtri at a distance of 11.2 cM from SSR marker Xwmc606.
TL;DR: Understanding of pathogenic mechanism causing CHD in DS cases along with the availability of emerging technologies has facilitated a novel discovery that has ultimately provided a better treatment and management for such cases.
Abstract: Congenital heart defects (CHD) affect 50% of Down's syndrome (DS) cases. This review focusses on the pathogenic molecular mechanism leading to the formation of DS-associated CHD along with the advancement of the emerging diagnostic techniques available for such patients in past few decades. We have shed light on the causative genes of DS-associated CHD that are located either on chromosome 21 or outside chromosome 21. Along with locus-specific mutation, numerous SNP and CNV, miRNA, use of maternal folic acid during pregnancy and signalling pathways are also reported to contribute to the formation of CHD in patients with DS. With the help of both these our understanding of pathogenic mechanism causing CHD in DS cases along with the availability of emerging technologies has facilitated a novel discovery that has ultimately provided a better treatment and management for such cases. Accurate diagnosis and treatment are now available with the introduction of CNV detection and NGS based approaches such as WES, WGS, target sequencing and sequencing of foetal cell-free DNA by the medical geneticist and cardiologist have now allowed further identification of familial recurrence risk and relatives who are at risk through genetic counselling, thereby providing reproductive options and improving proper care of DS-associated CHD. Further, gene-editing studies explore novel pathogenic mechanisms and signalling pathways in DS-associated CHD.
TL;DR: Multiple genes causing deafness were sequenced by next-generation sequencing to mean >80-100x coverage on Illumina sequencing platform and found variants in GJB2, WFS1, FGF3, EYA4, MYO7A, and CHD7 genes, which were pathogenic and novel, and possibly causative.
Abstract: Congenital deafness is one of the common disorders, with some common genes accounting for most of the cases. One in 1000 children are born with sensorineural hearing loss, and of that 50% are hereditary. In the Mediterranean Europeans, 80% of the nonsyndromic recessive deafness is due to homozygous mutation in GJB2, the 35del G allele. InWestern population, the GJB2 variation have been found in up to 30-40% cases. In Indians, the GJB2 variants have been found in up to 20% cases, mostly from central and southern India. In the present study, DNA was extracted from blood using standard methods. This was used to perform targeted gene capture using a custom capture kit. Multiple genes causing deafness were sequenced by next-generation sequencing to mean >80-100x coverage on Illumina sequencing platform. We found variants in GJB2, WFS1, FGF3, EYA4, MYO7A. and CHD7 genes. Most of these variants were pathogenic and novel, and possibly causative. Deafness is most commonly due to the autosomal dominant genes but in severe cases of early onset deafness, autosomal recessive genes may contribute in our population. In selected families of severe prelingual deafness, prenatal diagnosis can be done.