Showing papers in "Journal of Genetics in 2018"

Marker-assisted introgression of opaque2 allele for rapid conversion of elite hybrids into quality protein maize

Abstract: Maize is a valuable source of food and feed worldwide. Maize endosperm protein is, however nutritionally poor due to the reduced levels of two essential amino acids, lysine and tryptophan. In this study, recessive opaque2 (o2) allele that confers enhanced endosperm lysine and tryptophan, was introgressed using marker-assisted backcross breeding into three normal inbred lines (HKI323, HKI1105 and HKI1128). These are the parental lines of three popular medium-maturing single cross hybrids (HM4, HM8 and HM9) in India. Gene-based simple sequence repeat (SSR) markers (umc1066 and phi057) were successfully deployed for introgression of o2 allele. Background selection using genome-based SSRs helped in recovering > 96% of recurrent parent genome. The newly developed quality protein maize (QPM) inbreds showed modified kernels (25-50% opaqueness) coupled with high degree of phenotypic resemblance to the respective recipient lines, including grain yield. In addition, endosperm protein quality showed increased lysine and tryptophan in the inbreds to the range of 52-95% and 47-118%, respectively. The reconstituted QPM hybrids recorded significant enhancement of endosperm lysine (48-74%) and tryptophan (55-100%) in the endosperm. The QPM hybrids exhibited high phenotypic similarity with the original hybrids for morphological and yield contributing traits along with responses to some major diseases like turcicum leaf blight and maydis leaf blight. The grain yield of QPM hybrids was at par with their original versions under multilocation testing. These elite, high-yielding QPM hybrids with improved protein quality have been released and notified for commercial cultivation, and hold significant promise for improving nutritional security.

Selection and validation of reference genes for normalization of qRT-PCR gene expression in wheat (Triticum durum L.) under drought and salt stresses

Abstract: Eight candidate housekeeping genes were examined as internal controls for normalizing expression analysis of durum wheat (Triticum durum L.) under drought and salinity stress conditions. Quantitative real-time PCR was used to analyse gene expression of multiple stress levels, plant ages (24 and 50 days old), and plant tissues (leaf and root). The algorithms BestKeeper, NormFinder, GeNorm, the delta Ct method and the RefFinder were applied to determine the stability of candidate genes. Under drought stress, the most stable reference genes were glyceraldehyde-3 phosphate, ubiquitin and β-tubulin2, whereas under salinity stress conditions, eukaryotic elongation factor 1-α, glyceraldehyde-3 phosphate and actin were identified as the most stable reference genes. Validation with stress-responsive genes NAC29 and NAC6 demonstrated that the expression level of target genes could be determined reliably with combinations of up to three of the reference genes. This is the first report on reference genes appropriate for quantification of target gene expression in T. durum under drought and salt stresses. Results of this investigation may be applicable to other Triticum species.

(New) Species concepts, species delimitation and the inherent limitations of taxonomy

Abstract: The species problem, despite decades of heated debates, has not been resolved yet. Recently, two new species concepts have been published, the mitonuclear compatibility species concept and the inclusive species concept. I briefly discuss them, together with a recent attempt at standardizing taxonomic decisions, in the broader framework of what I believe is an inherent limitation of taxonomy-imposing a discrete system on a continuous process (evolution) that leads to fuzzy boundaries in nature. In the light of this, taxonomists, biologists in general and conservationists alike will have to accept the fact that completely nonarbitrary species delimitation is impossible. This has serious ramifications in all disciplines that rely on species, and particularly species counts, as a basic currency for quantitative analyses (ecology, evolutionary biology) and practical decision-making (conservation and environmental policy).

Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks.

Abstract: Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are pressing health concerns in modern societies for which effective therapies are still lacking. Recent high-throughput genomic technologies have enabled genome-scale, multidimensional investigations to facilitate a better understanding of the underlying mechanisms and the identification of novel targets. Here we review the molecular insights gained through such studies, and compare the similarities and differences between neurodegenerative diseases revealed by systems genomics and gene network modelling approaches. We focus specifically on the shared mechanisms at multiple molecular scales ranging from genetic factors to gene expression to network-level features of gene regulation, and whenever possible also point out mechanisms that distinguish one disease from another. Our review sets the stage for similar genomewide inspection in the future on shared/distinct features of neurodegenerative diseases at the levels of cellular, proteomic or epigenomic signatures, and how these features may interact to determine the progression and treatment response of different diseases afflicting the same individual.

Huntington's disease: the coming of age.

Abstract: Huntington’s disease (HD) is caused due to an abnormal expansion of polyglutamine repeats in the first exon of huntingtin gene. The mutation in huntingtin causes abnormalities in the functioning of protein, leading to deleterious effects ultimately to the demise of specific neuronal cells. The disease is inherited in an autosomal dominant manner and leads to a plethora of neuropsychiatric behaviour and neuronal cell death mainly in striatal and cortical regions of the brain, eventually leading to death of the individual. The discovery of the mutant gene led to a surge in molecular diagnostics of the disease and in making different transgenic models in different organisms to understand the function of wild-type and mutant proteins. Despite difficult challenges, there has been a significant increase in understanding the functioning of the protein in normal and other gain-of-function interactions in mutant form. However, there have been no significant improvements in treatments of the patients suffering from this ailment and most of the treatment is still symptomatic. HD warrants more attention towards better understanding and treatment as more advancement in molecular diagnostics and therapeutic interventions are available. Several different transgenic models are available in different organisms, ranging from fruit flies to primate monkeys, for studies on understanding the pathogenicity of the mutant gene. It is the right time to assess the advancement in the field and try new strategies for neuroprotection using key pathways as target. The present review highlights the key ingredients of pathology in the HD and discusses important studies for drug trials and future goals for therapeutic interventions.

Transcriptional modulation of entire chromosomes: dosage compensation

Abstract: Dosage compensation is a regulatory system designed to equalize the transcription output of the genes of the sex chromosomes that are present in different doses in the sexes (X or Z chromosome, depending on the animal species involved). Different mechanisms of dosage compensation have evolved in different animal groups. In Drosophila males, a complex (male-specific lethal) associates with the X chromosome and enhances the activity of most X-linked genes by increasing the rate of RNAPII elongation. In Caenorhabditis, a complex (dosage compensation complex) that contains a number of proteins involved in condensing chromosomes decreases the level of transcription of both X chromosomes in the XX hermaphrodite. In mammals, dosage compensation is achieved by the inactivation, early during development, of most X-linked genes on one of the two X chromosomes in females. The mechanism involves the synthesis of an RNA (Tsix) that protects one of the two Xs from inactivation, and of another RNA (Xist) that coats the other X chromosome and recruits histone and DNA modifying enzymes. This review will focus on the current progress in understanding the dosage compensation mechanisms in the three taxa where it has been best studied at the molecular level: flies, round worms and mammals.

Maintenance of multipartite genome system and its functional significance in bacteria

Abstract: Bacteria are unicellular organisms that do not show compartmentalization of the genetic material and other cellular organelles as seen in higher organisms. Earlier, bacterial genomes were defined as single circular chromosome and extrachromosomal plasmids. Recently, many bacteria were found harbouring multipartite genome system and the numbers of copies of genome elements including chromosomes vary from one to several per cell. Interestingly, it is noticed that majority of multipartite genome-harbouring bacteria are either stress tolerant or pathogens. Further, it is observed that the secondary genomes in these bacteria encode proteins that are involved in bacterial genome maintenance and also contribute to higher stress tolerance, and pathogenicity in pathogenic bacteria. Surprisingly, in some bacteria the genes encoding the proteins of classical homologous recombination pathways are present only on the secondary chromosomes, and some do not have either of the classical homologous recombination pathways. This review highlights the presence of ploidy and multipartite genomes in bacterial system, the underlying mechanisms of genome maintenance and the possibilities of these features contributing to higher abiotic and biotic stress tolerance in these bacteria.

Lafora disease: from genotype to phenotype.

Abstract: The progressive myoclonic epilepsy of Lafora or Lafora disease (LD) is a neurodegenerative disorder characterized by recurrent seizures and cognitive deficits. With typical onset in the late childhood or early adolescence, the patients show progressive worsening of the disease symptoms, leading to death in about 10 years. It is an autosomal recessive disorder caused by the loss-of-function mutations in the EPM2A gene, coding for a protein phosphatase (laforin) or the NHLRC1 gene coding for an E3 ubiquitin ligase (malin). LD is characterized by the presence of abnormally branched water insoluble glycogen inclusions known as Lafora bodies in the neurons and other tissues, suggesting a role for laforin and malin in glycogen metabolic pathways. Mouse models of LD, developed by targeted disruption of the Epm2a or Nhlrc1 gene, recapitulated most of the symptoms and pathological features as seen in humans, and have offered insight into the pathomechanisms. Besides the formation of Lafora bodies in the neurons in the presymptomatic stage, the animal models have also demonstrated perturbations in the proteolytic pathways, such as ubiquitin-proteasome system and autophagy, and inflammatory response. This review attempts to provide a comprehensive coverage on the genetic defects leading to the LD in humans, on the functional properties of the laforin and malin proteins, and on how defects in any one of these two proteins result in a clinically similar phenotype. We also discuss the disease pathologies as revealed by the studies on the animal models and, finally, on the progress with therapeutic attempts albeit in the animal models.

Neurodegenerative diseases: model organisms, pathology and autophagy

Abstract: A proteostasis view of neurodegeneration (ND) identifies protein aggregation as a leading causative reason for damage seen at the cellular and organ levels. While investigative therapies that aim at dissolving aggregates have failed, and the promises of silencing expression of ND associated pathogenic proteins or the deployment of engineered induced pluripotent stem cells (iPSCs) are still in the horizon, emerging literature suggests degrading aggregates through autophagy-related mechanisms hold the current potential for a possible cure. Macroautophagy (hereafter autophagy) is an intracellular degradative pathway where superfluous or unwanted cellular cargoes (such as peroxisomes, mitochondria, ribosomes, intracellular bacteria and misfolded protein aggregates) are wrapped in double membrane vesicles called autophagosomes that eventually fuses with lysosomes for their degradation. The selective branch of autophagy that deals with identification, capture and degradation of protein aggregates is called aggrephagy. Here, we cover the workings of aggrephagy detailing its selectivity towards aggregates. The diverse cellular adaptors that bridge the aggregates with the core autophagy machinery in terms of autophagosome formation are discussed. In ND, essential protein quality control mechanisms fail as the constituent components also find themselves trapped in the aggregates. Thus, although cellular aggrephagy has the potential to be upregulated, its dysfunction further aggravates the pathogenesis. This phenomenon when combined with the fact that neurons can neither dilute out the aggregates by cell division nor the dead neurons can be replaced due to low neurogenesis, makes a compelling case for aggrephagy pathway as a potential therapeutic option.

A genome scan for quantitative trait loci affecting average daily gain and Kleiber ratio in Baluchi Sheep.

Abstract: Genomewide association study (GWAS) is an efficient tool for the detection of SNPs and candidate genes in quantitative traits. Growth rate is an important trait for increasing the meat production in sheep. A total of 96 Baluchi sheep were genotyped using Illumina Ovine SNP50 BeadChip to run a GWAS for an average daily gain (ADG) and Kleiber ratio (KR) traits in different periods of age in sheep. Traits included were average daily gain from birth to three months (ADG0-3), from three months to six months (ADG3-6), from six months to nine months (ADG6-9), from nine months to yearling (ADG9-12), from birth to six months (ADG0-6), from three months to nine months (ADG3-9), from three months to yearling (ADG3-12) and corresponding Kleiber ratios (KR0-3, KR3-6, KR6-9, KR9-12, KR0-6, KR3-9 and KR3-12, respectively). A total of 42,243 SNPs passed the quality-control filters and were analysed by PLINK software in a linear mixed model. Two SNPs were identified on two chromosomes at the 5% genomewide significance level for KR(3-9) and KR(6-9). Two candidate genes, namely MAGI1 and ZNF770, were identified correspondingly harbouring and close to these QTL. Also, a total of 21 SNPs were found on chromosomes 2, 3, 5, 6, 7, 10, 17, 19, 20 and 25 at the 5% chromosomewide significance level for ADG and KR traits. Thus, we suggest more studies to discover the causative variants for growth traits in sheep.

The jasmonate-responsive transcription factor CbWRKY24 regulates terpenoid biosynthetic genes to promote saponin biosynthesis in Conyza blinii H. Lév.

Abstract: Conyza blinii H. Lev., the most effective component is saponin, is a biennial medicinal material that needs to be overwintered. WRKY transcription factors family is a large protein superfamily that plays a predominant role in plant secondary metabolism, but their characteristics and functions have not been identified in C. blinii. The CbWRKY24 sequence was selectedfrom the transcriptome database of the C. blinii leaves constructed in our laboratory. Phylogenetic tree analysis revealed that it was associated with AaWRKY1 which can regulate artemisinin synthesis in Artemisia annua. Expression analysis in C. blinii revealed that CbWRKY24 was mainly induced by methyl jasmonate (MeJA) and cold treatments. Transcriptional activity assay showed that it had an independent biological activity. Overexpression of CbWRKY24 in transient transformed C. blinii resulted in improved totalsaponins content, which was attributed to upregulate the expression level of keys genes from mevalonate (MVA) pathway in transient transformed plants compared to wild type (WT) plants. Meanwhile, overexpression the CbWRKY24 in transient transformed tomato fruits showed that the transcript level of related genes in lycopene pathway decreased significantly when compared to WT tomatofruits. Additionally, the MeJA-response-element was found in the promoter regions of CbWRKY24 and the histochemical staining experiments showed that promoter had GUS activity in transiently transformed tobacco leaves. In summary, our results indicated that we may have found a transcription factor that can regulate the biosynthesis of terpenoids in C. blinii.

Analysis of genetic diversity and population structure in upland cotton (Gossypium hirsutum L.) germplasm using simple sequence repeats.

Abstract: Improvement of cotton fibre yield and quality is challenging due to the narrow genetic base of modern cotton cultivars, which emphasizes the great need to effectively explore the existing germplasm resources. With major objective to assess the genetic diversity and population structure at DNA level, 302 elite upland cotton germplasm accessions (253 Chinese and 49 different exotic origins), were genotyped using 198 simple sequence repeats (SSRs) markers. Each of the 198 markers differed greatly in its ability to detect variations in the panel of cotton germplasm. The SSRs amplified 897 alleles, of which 77.7% were polymorphic. The number of alleles varied from 2 to 12 (mean 4.53). Gene diversity ranged from 0.020 to 0.492 with a mean of 0.279. The polymorphic information content (PIC) values ranged from 0.371 to 0.019 (mean 0.225). Genetic distances in the whole cotton germplasm ranged from 0.451 to 0.052 (mean 0.270), demonstrating relatively wider genetic diversity range. Chinese-origin cotton germplasm showed the highest level of SSR polymorphisms (gene diversity $$=$$ 0.268, PIC $$=$$ 0.218), whereas American-origin revealed the highest mean genetic distance (0.274). Model-based Bayesian analysis clustered the whole cotton germplasm into three subpopulations, and the highest molecular variation ws revealed between subpopulations (4%, $$P{<} 0.001$$ ). The SSRs revealed moderate level of genetic diversity at DNA level, identified three structured subpopulations, suggesting a potential use of these markers for genomewide association mapping studies and for identifying and conserving useful alleles in upland cotton germplasm.

Meta-analysis of genetic polymorphisms in xenobiotic metabolizing enzymes and their association with breast cancer risk

Abstract: Studies on the association of cytochrome p450 A1 (m1, m2), catechol-O-methyltransferase (COMT) H108L, glutathione S-transferase (GST) T1 and M1 polymorphisms with breast cancer risk were inconclusive. The current study was aimed to clarify the ambiguity in genetic associations of these enzymes with breast cancer risk on a global perspective. A systematic literature search was carried out in PubMed, Google Scholar and Medline, covering all the case-control studies published until September 2017. A meta-analysis was performed based on the random-effect and fixed-effect models to calculate the overall association of each genetic variant with breast cancer risk. Of the five polymorphisms studied, GSTT1 (OR: 1.07, 95% CI: 1.02-1.12 and OR: 1.08, 95% CI: 1.01-1.15 for fixed-effect and random-effect models, respectively) and GSTM1 (OR: 1.22, 95% CI: 1.17-1.26 and OR: 1.25, 95% CI: 1.12-1.35 for fixed-effect and random-effect models, respectively) null polymorphisms exhibited an increased risk for breast cancer in both the models. Cochrane Q-test and I² statistics revealed heterogeneity in association with these polymorphisms (P< 0.0001) with no evidence of publication bias. Thus, GSTT1 and GSTM1 null polymorphisms are risk factors for breast cancer.

Parkinson's disease: what the model systems have taught us so far

Abstract: Parkinson's disease (PD) is a debilitating neurodegenerative disorder, for which people above the age of 60 show an increased risk Although there has been great advancement in understanding the disease-related abnormalities in brain circuitry and development of symptomatic treatments, a cure for PD remains elusive The discovery of PD associated gene mutations and environmental toxins have yielded animal models of the disease These models could recapitulate several key aspects of PD, and provide more insights into the disease pathogenesis They have also revealed novel aspects of the disease mechanism including noncell autonomous events and spreading of pathogenic protein species across the brain Nevertheless, none of these models so far can comprehensively represent all aspects of the human disease While the field is still searching for the perfect model system, recent developments in stem cell biology have provided a new dimension to modelling PD, especially doing it in a patient-specific manner In the current review, we attempt to summarize the key findings in the areas discussed above, and highlight how the core PD pathology distinguishes itself from other neurodegenerative disorders while also resembling them in many aspects

Genetic variations in influx transporter gene SLC22A1 are associated with clinical responses to imatinib mesylate among Malaysian chronic myeloid leukaemia patients

Abstract: Imatinib mesylate (IM), a well-established gold standard drug in the treatment of chronic myeloid leukaemia (CML), is a synthetic tyrosine kinase inhibitor. Despite excellent efficacy, a significant number of patients on IM therapy develop resistance to IM. Currently, great focus has been laid on the effect of interindividual pharmacogenetic variability on IM treatment responses. IM uptake is mediated by the hOCT1 protein encoded by the solute carrier 22 gene (SLC22A1). The current study investigated the impact of few single-nucleotide polymorphisms (SNPs) of SLC22A1 on mediating resistance and/or good response to IM among 278 Malaysian CML patients (146 IM-resistant group and 132 IM good response group) undergoing IM therapy on 400 mg daily. Our results showed that the allelic frequencies of heterozygous (CG) and homozygous variant (GG) genotypes of SLC22A1 C480G were significantly higher in the IM-resistant group compared with the IM good response group (41.8% versus 30.3% and 10.9% versus 4.5% with P values of 0.047 and 0.048, respectively). On evaluating the association of genotypes with risk of IM resistance development, heterozygous (CG) and homozygous (GG) variant genotypes showed significantly higher risk for developing resistance to IM treatment with odds ratio (OR): 1.901 (95% confidence interval (CI): 1.142-3.163, P = 0.013) and 3.324 (95% CI: 1.235-8.947, P = 0.017), respectively. Two SNPs and two insertions/deletions were detected in exon 7 of SLC22A1. For exon 7, 1222AA carriers together with the presence of both the 8-bp insertion and 3-bp deletion, and M420del alleles showed higher possibility of developing resistance towards IMtreatment. Our results warrant the need of genotyping this SNP in terms of modulating IM treatment in CML patients.

Therapeutic avenues for hereditary forms of retinal blindness.

Abstract: Hereditary retinal diseases, known as retinal degenerations or dystrophies, are a large group of inherited eye disorders resulting in irreversible visual loss and blindness. They develop due to mutations in one or more genes that lead to the death of the retinal photoreceptor cells. Till date, mutations in over 200 genes are known to be associated with all different forms of retinal disorders. The enormous genetic heterogeneity of this group of diseases has posedmany challenges in understanding the mechanisms of disease and in developing suitable therapies. Therapeutic avenues that are being investigated for these disorders include gene therapy to replace the defective gene, treatment with neurotrophic factors to stimulate the growth of photoreceptors, cell replacement therapy, and prosthetic devices that can capture light and transmit electrical signals through retinal neurons to the brain. Several of these are in process of human trials in patients, and have shown safety and efficacy of the treatment. A combination of approaches that involve both gene replacement and cell replacement may be required for optimum benefit.

Oestrogen regulates the expression of cathepsin E-A-like gene through ERΒ in liver of chicken (Gallus gallus).

Abstract: The cathepsin E-A-like, also known as 'similar to nothepsin', is a new member of the aspartic protease family, which may take part in processing of egg yolk macromolecules, due to it was identified in the chicken egg-yolk. Previously, studies have suggested that the expression of cathepsin E-A-like increased gradually during sexual maturation of pullets, but the exact regulation mechanism is poorly understood. In this study, to gain insight into the function and regulation mechanism of the gene in egg-laying hen, we cloned the cathepsin E-A-like gene and evaluated its evolutionary origin by using both phylogenetic and syntenic methods. The mode of the gene expression regulation was analysed through stimulating juvenile hens with 17β-estradiol and chicken embryo hepatocytes with 17β-estradiol combined with oestrogen receptor antagonists including MPP, ICI 182,780 and tamoxifen. Our results showed that cathepsin E-A-like was an orthologoues gene with nothepsin, which is present in birds but not in mammals. The expression of cathepsin E-A-like significantly increased in a dose-dependent manner after the juvenile hens were treated with 17β-estradiol (P < 0.05). Compared with the 17β-estradiol treatment group, the expression of cathepsin E-A-like was not significantly changed when the hepatocytes were treated with 17β-estradiol combined with MPP (P < 0.05). In contrast, compared with the 17β-estradiol combined with MPP treatment group, the expression of cathepsin E-A-like was significantly downregulated when the hepatocytes were treated with 17β-estradiol combined with tamoxifen or ICI 182,780 (P < 0.05). These results demonstrated that cathepsin E-A-like shared the same evolutionary origin with nothepsin. The expression of cathepsin E-A-like was regulated by oestrogen, and the regulative effect was predominantly mediated through ER-Β in liver of chicken.

MiR-27b promotes sheep skeletal muscle satellite cell proliferation by targeting myostatin gene.

Abstract: To investigate the role of miR-27b in sheep skeletal muscle development, here we first cloned the sequence of sheep pre-miR-27b, then further investigated its expression pattern in sheep skeletal muscle in vivo, the relationship of miR-27b expression and sheep skeletal muscle satellite cell proliferation and differentiation in vitro, and then finally confirmed its target gene during this development process. MiR-27b sequence, especially its mature sequence, was conservative among different species. MiR-27b highly expressed in sheep skeletal muscle than other tissues. In skeletal muscle of Suffolk and Bashbay sheep, miR-27b was upregulated during foetal period and downregulated during postnatal period significantly (P<0.01), but it still kept a relatively higher expression level in skeletal muscle of postnatal Suffolk sheep than Bashbay. There is a potential target site of miR-27b on 3'-UTR of sheep myostatin (MSTN) mRNA, and the double luciferase reporter assay proved that miR-27b could successfully bind on this site. When sheep satellite cells were in the proliferation status, miR-27b was upregulated and MSTN was downregulated significantly (P<0.01). When miR-27b mimics was transfected into sheep satellite cells, the cell proliferation was promoted and the protein level of MSTN was significantly downregulated (P<0.01). Moreover, miR-27b regulated its target gene MSTN by translation repression at an early step, and followed by inducing mRNA degradation in sheep satellite cells. Based on these results, we confirm that miR-27b could promote sheep skeletal muscle satellite cell proliferation by targeting MSTN and suppressing its expression.

Phylogenetic analysis and evolution of morphological characters in the genus Jasminum L. (Oleaceae) in India.

Abstract: Jasminum L. (Oleaceae) consists of ∼200 species that are distributed in tropical, subtropical and temperate regions of the world. In India, this genus is represented by ca 47 species of which 16 are endemic. Based on the nuclear (internal-transcribed spacer (ITS) region of nrDNA and chloroplast markers (matK, trnL-F and trnH-psbA), phylogenetic relationships in 22 species including one variety of Jasminum in India have been assessed. Maximum likelihood and Bayesian analyses from individual markers, as well as from combined dataset, reveal that the group is monophyletic if Menodora spp. are excluded from the analyses. Our analyses recovered three strongly supported clades. Ancestral character state reconstruction of taxonomically useful characters (leaf forms, leaf arrangement and flower colour) which were used to demarcate sections within the genus reveals homoplasy. Our study suggests that after split from the last common ancestor, there have been at least four reversals to unifoliolate condition. Pinnately compound leaf form evolved at least twice and trifoliolate condition evolved one time only. Alternate leaf form evolved at least twice, once inclade 1 and once in clade 3 and all the time from ancestors having opposite leaf forms. Flower colour evolution clearly depicts that clade 1 is yellow-flowered and clades 2 and 3 have admixture of white and yellow-flowered Jasminum species. Our study suggests that yellow-flowered condition evolved from the white-flowered ancestor. The present study is first to estimate the evolutionary history of Indian Jasmines.

MicroRNA-197 induces epithelial-mesenchymal transition and invasion through the downregulation of HIPK2 in lung adenocarcinoma.

Abstract: The major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD) is due to distant metastasis. Many reports have indicated that miRNA plays a key role in tumour metastasis. The expression of miR-197 is correlated with LADprogression, however, the mechanism of miR-197 is still unknown in the processing of LAD. A Boyden chamber migration/invasion assay was used for the metastatic function study in vitro. Real-time PCR andWestern blot assays were employed to analyse the EMT hallmark changes in both the mRNA and protein levels. 3'-UTR reporter luciferase assay was used to show that HIPK2 is a directtarget of miR-197. miR-197 enhances LAD cell migration and invasion miR-197. The downregulation of miR-197 suppresses the EMT and migration ability. HIPK2 is a direct functional target of miR-197 in LAD metastasis. In summary, miR-197 controls EMT and metastasis by directly silencing HIPK2. The findings suggest that interfering with the miR-197-dependent regulation of HIPK2 could be a useful approach for the treatment of patients with late stage metastatic LAD.

Identification of high-efficiency SSR markers for assessing watermelon genetic purity.

Abstract: Genomic simple sequence repeat (SSR) markers were used to fingerprint and determine genetic similarity (GS) of the watermelon breeding lines, as well as the purity of their hybrid derivatives. Cluster analysis and Jaccard’s distance coefficients using the unweighted pair group method with arithmetic mean (UPGMA) have classified these lines into three major groups. Notwithstanding, the genetic background of these lines is narrow as revealed by the restricted GS coefficients. Fifty-five sets of SSR markers were employed in this study. Fourteen of these markers were polymorphic between the breeding lines and were used for assessing hybrid purity. Cross-checking assay validated nine SSR markers as informative SSR markers for purity detection of these hybrids. To confirm the accuracy and efficiency of these markers, their derived PCR products were further sequenced, and ClSSR09643, ClSSR18153 and ClSSR01623 were selected as high-efficiency SSR markers. Interestingly, SSR markers ClSSR09643 and ClSSR18153 were broadly applied for purity detection of more than two different hybrids, while SSR marker ClSSR01623 behaved as a specific marker for purity detection in this study. Genetic purity of six commercial watermelon hybrids was definitely evaluated using these SSR markers. Genetic purity of all tested hybrids exceeded 96% while the field purity was above 98%. Genetic purity test was an emergency for identifying off-types and selfed female in a lot of hybrid seeds. Here, we elucidated the potential of nine SSR markers including three with higher breeding selection efficiency. We recommended them to seed company for purity improvement of watermelon commercial hybrid varieties.

Identification of novel microsatellite markers in okra (Abelmoschus esculentus (L.) Moench) through next-generation sequencing and their utilization in analysis of genetic relatedness studies and cross-species transferability

Abstract: Abelmoschus esculentus L. (Malvaceae), populary known as okra, is one of the important pod vegetable crops in tropics and subtropics. To develop the microsatellite markers, we have partially sequenced genomic DNAusing Roche 454 Titanium pyrosequencing technology. A total of 979,806 bp data from 61,722 reads were obtained. These reads were assembled into 3735 contigs of which 2708 had microsatellites. Primers were designed for 402 microsatellites, from which 50 randomly selected SSR primerswere standardized for amplification of okraDNA. Genetic analysis was done by employing 29 genotypes. Polymorphic information content (PIC) across all 50 loci ranged from 0.000 to 0.865 with a mean value of 0.519. The observed and expected heterozygosity ranged from 0.000 to 0.750 and 0.000 to 0.972, respectively. Alleles per locus ranged from 1 to 27. This is the first report on the development of genomic SSR markers in okra using next-generation sequencing technology. We have also assessed cross species transferability of microsatellite markers with related wild speciesA. tetraphyllus (84%),A. ficulneus (78%), A. moschatus (92%), A. angulosus grandiflorus (90%) and A. caillei (86%), and demonstrated their use in genetic relatedness study and molecular characterization. Okra (Abelmoschus esculentus L.) belongs to the family Malvaceae and is considered as one of the important pod vegetable crops in India, Southeast Asia,West Africa, USA, Brazil and Turkey. Okra is rich in calcium, mineral salt, and vitamins (Aladele et al. 2008). The total production of okra in the world is around 4.8 million ton pods with highly mucilage, where India contributes 70% Nigeria 15%, Pakistan 2%, Ghana 2%, Egypt 1.7%, and Iraq 1.7% (Gulsen et al. 2007).The genus Abelmoschus includes eight species (RamyaandBhat 2012).The genome size of okra is 1.6 Gb, and the chromosome number is generally found tobe 2n = 130 (Joshi andHardas 1956).There are two kinds of A. esculentus L. genotypes 2n = 60−70 as diploid and 2n = 120−130 as tetraploids, this variation in chromosome number could be due to irregularities in chromosome movement during the mitotic phase of cell division (Nwangburuka et al. 2011). The polyploidy complex was further assessed through chloroplast DNA (cpDNA) intronic spacer, which revealed that A. ficulneus and A. moschatus are the closest wild relatives of A. esculentus (Ramya and Bhat 2012). Molecular markers have proved as a powerful tool for the assessment of genetic variation and elucidation of genetic relationships within and among the species (Chakravarthi and Naravaneni 2006; Yuan et al. 2014, 2015). Molecular marker techniques like RAPD, RFLP, simple sequence repeat (SSR) and AFLP are the most widely used for the genetic characterization of species and also for the crop improvement (Sawadogo et al. 2009).

Interleukin gene polymorphisms and susceptibility to HIV-1 infection: a meta-analysis.

Abstract: Some subjects are repeatedly exposed to human immunodeficiency virus (HIV), yet they remain uninfected. This suggests the existence of host-resistance mechanisms. The current study synthesizes the evidence regarding the association between interleukin (IL) gene polymorphisms and HIV susceptibility. Medline, Scopus and the Web of Science databases were systematically searched, and a meta-analysis of case–control studies was conducted. Univariate and bivariate methods were used. The literature search identified 42 eligible studies involving 15,727 subjects. Evidence was obtained on eight single-nucleotide polymorphisms (SNPs): IL1A −889 C>T (rs1800587), IL1B +3953/4 C>T (rs1143634), IL4 −589/90 C>T (rs2243250), IL6 −174 G>C (rs1800795), IL10 −592 C>A (rs1800872), IL10−1082 A>G (rs1800896), IL12B −1188 A>C (rs3212227) and IL28B C>T (rs12979860). The IL1B +3953/4 C>T variant appears to increase the risk of HIV acquisition, under the assumption of a recessive genetic model (odds ratio (OR): 4.47, 95% CI: 2.35–8.52). The AA homozygotes of the IL10 -592 C>A SNP had an increased, marginally nonsignificant, risk (OR: 1.39, 95% CI: 0.97–2.01). It reached, however, significance in subanalyses (OR: 1.49, 95% CI: 1.04–2.12). Finally, the well-studied hepatitis C virus (HCV) infection IL28B (rs12979860) CT/TT genotypes were associated with a 27% decrease in HIV infection risk, especially in populations infected with HCV (OR: 0.73, 95% CI: 0.57–0.95). Interleukin signalling is perhaps important in HIV infection and some interleukin genetic variants may affect the risk of HIV acquisition. Approaches targeting specific genes and genomewide association studies should be conducted to decipher the effect of these polymorphisms.

Regulation of membrane dynamics by Parkinson’s disease-associated genes

Abstract: Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, develops sporadically, and its cause is unknown. However, 5–10% of PD cases are inherited as monogenic diseases, which provides a chance to understand the molecular mechanisms underlying neurodegeneration. Over 20 causative genes have already been identified and are being characterized. These PD-associated genes are broadly classified into two groups: genes involved in mitochondrial functions and genes related to membrane dynamics such as intracellular vesicle transport and the lysosomal pathway. In this review, we summarize the latest findings on the mechanism by which members of the latter group of PD-associated genes regulate membrane dynamics, and we discuss how mutations of these genes lead to dopaminergic neurodegeneration.

Schinzel–Giedion syndrome: a novel case, review and revised diagnostic criteria

Abstract: Schinzel-Giedion syndrome (SGS) is a rare autosomal dominant inheritance disorder. Heterozygous de novo mutations in the SETBP1 gene have been identified as the genetic cause of SGS. Here, we report a novel case with the syndrome with a novel insertion mutation in SETBP1. We also present a review of SGS cases, and first revise diagnostic criteria of SGS based on clinicalfindings and/or SETBP1 mutation worldwide. A revised diagnostic criteria and typing of SGS can be determined. Type I (complex and classic type) SGS patients present a development delay and typical facial features (prominent forehead, midface retraction, and short and upturned nose) associated with hydronephrosis or two of the characteristic skeletal anomalies (a sclerotic skull base, wideoccipital synchondrosis, increased cortical density or thickness, and broad ribs). Type II (middle type) patients show development delay and the distinctive facial phenotype (midface retraction, short and upturned nose), lacking both hydronephrosis and typical skeletal abnormalities, with existence of SETBP1mutation. Type III (simple type) patients with SETBP1 alteration show their major symptom is development delay, in which expressive language delay is the most striking feature. Central nervous system involvement with development delay in which expressive language delay is much more obviously affected is the most prominent feature of SGS. There is another indication that severity of phenotype of SGS may be inversely correlated with degree of SETBP1 alteration, besides gain-of-function or dominant-negative effects in SETBP1 alteration causing SGS.

Advances in the discovery of genetic risk factors for complex forms of neurodegenerative disorders: contemporary approaches, success, challenges and prospects.

Abstract: Neurodegenerative diseases constitute a large proportion of disorders in elderly, majority being sporadic in occurrence with $$\sim $$ 5–10% familial. A strong genetic component underlies the Mendelian forms but nongenetic factors together with genetic vulnerability contributes to the complex sporadic forms. Several gene discoveries in the familial forms have provided novel insights into the pathogenesis of neurodegeneration with implications for treatment. Conversely, findings from genetic dissection of the sporadic forms, despite large genomewide association studies and more recently whole exome and whole genome sequencing, have been limited. This review provides a concise account of the genetics that we know, the pathways that they implicate, the challenges that are faced and the prospects that are envisaged for the sporadic, complex forms of neurodegenerative diseases, taking four most common conditions, namely Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington disease as examples. Poor replication across studies, inability to establish genotype–phenotype correlations and the overall failure to predict risk and/or prevent disease in this group poses a continuing challenge. Among others, clinical heterogeneity emerges as the most important impediment warranting newer approaches. Advanced computational and system biology tools to analyse the big data are being generated and the alternate strategy such as subgrouping of case–control cohorts based on deep phenotyping using the principles of Ayurveda to overcome current limitation of phenotype heterogeneity seem to hold promise. However, at this point, with advances in discovery genomics and functional analysis of putative determinants with translation potential for the complex forms being minimal, stem cell therapies are being attempted as potential interventions. In this context, the possibility to generate patient derived induced pluripotent stem cells, mutant/gene/genome correction through CRISPR/Cas9 technology and repopulating the specific brain regions with corrected neurons, which may fulfil the dream of personalized medicine have been mentioned briefly. Understanding disease pathways / biology using this technology, with implications for development of novel therapeutics are optimistic expectations in the near future.

Mapping QTL controlling agronomic traits in a doubled haploid population of winter oilseed rape (Brassica napus L.)

Abstract: Identification of superior alleles for agronomic traits in genetic resources of oilseed rape (Brassica napus L.) would be useful for improving the performance of locally adapted cultivars in Iran. The objective of the present work was to analyse the genetic variation and inheritance of important agronomic traits in a doubled haploid population derived from a cross between two German oilseed rape cultivars, Sansibar and Oase. Field experiments were performed in 2016–2017 with 200 doubled haploid lines and the parental genotypes applying an alpha-lattice design with two replicates. Phenological traits were recorded during the cultivation period and at maturity, seed yield, yield components and seed quality traits were determined. Significant genetic variation was found in most of the traits and heritabilities ranged from medium (48.5%) for days to end of flowering to high (92.6%) for oil content. A molecular marker linkage map was used to map 36 QTL for different traits on 17 linkage groups. Between three and four QTL were identified for each seed yield, seed weight, oil and protein content. Some of the plant material and positive QTL alleles identified for agronomic traits may be useful for improving those characters in locally adapted cultivars in Iran.

Development and characterization of chloroplast microsatellite markers for Pinus massoniana and their application in Pinus (Pinaceae) species.

Abstract: Pinus massoniana is one of the important afforestation and pioneer tree species, which is widely distribute in southern China. Chloroplast simple sequence repeat markers (cpSSRs) have been widely used in studies of tree genetics, phylogenetic and breeding. We sequenced the whole chloroplast genome sequences of P. massoniana using PCR and Sanger sequencing. A total of 71 cpSSRs were identified, among which mononucleotide repeats were predominant (70.42%). Seventeen primer pairs were developed and amplification tests were conducted with 15 P. massoniana individuals. Also, cross-species amplification tests were conducted among 15 individuals per Pinus species, including P. elliottii, P. bungeana, P. armandii, P. caribaea, P. tabulaeformis, P. taiwanensis and P. yunnanensis which revealed polymorphic information content ranging from 0.2 to 0.8 and average of haploid diversity (h) ranging from 0.29 to 0.63. In addition, the polymorphic cpSSRs were useful in distinguishing the sampled pine species, and could be powerful tool in phylogenetic studies.

Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy.

Abstract: Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.

Genetic testing for clinically suspected spinocerebellar ataxias: report from a tertiary referral centre in India.

Abstract: Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative syndromes, characterized by a wide range of muscular weakness and motor deficits, caused due to cerebellar degeneration. The prevalence of the syndromes of SCA varies across the world and is known to be linked to the instability of trinucleotide repeats within the high-end normal alleles, along with susceptible haplotype. We estimated sizes of the CAG or GAA repeat expansions at the SCA1, SCA2, SCA3, SCA12 and frataxin loci among 864 referrals of subjects to genetic counselling and testing (GCAT) clinic, National Institute of Mental Health and Neurosciences, Bengaluru, India, with suspected SCA. The most frequent mutations detected were SCA1 ( $$n=100$$ (11.6%)) and SCA2 ( $$n=98$$ (11.3%)) followed by SCA3 ( $$n=40$$ (4.6%)), FRDA ( $$n=20$$ (2.3%)) and SCA12 ( $$n=8$$ (0.9%)).