Number Of Potential Genes Research Articles

Potential Therapeutic Candidates against Chlamydia pneumonia Discovered and Developed In Silico Using Core Proteomics and Molecular Docking and Simulation-Based Approaches.

Chlamydia pneumonia, a species of the family Chlamydiacea, is a leading cause of pneumonia. Failure to eradicate C. pneumoniae can lead to chronic infection, which is why it is also considered responsible for chronic inflammatory disorders such as asthma, arthritis, etc. There is an urgent need to tackle the major concerns arising due to persistent infections caused by C. pneumoniae as no FDA-approved drug is available against this chronic infection. In the present study, an approach named subtractive proteomics was employed to the core proteomes of five strains of C. pneumonia using various bioinformatic tools, servers, and software. However, 958 non-redundant proteins were predicted from the 4754 core proteins of the core proteome. BLASTp was used to analyze the non-redundant genes against the proteome of humans, and the number of potential genes was reduced to 681. Furthermore, based on subcellular localization prediction, 313 proteins with cytoplasmic localization were selected for metabolic pathway analysis. Upon subsequent analysis, only three cytoplasmic proteins, namely 30S ribosomal protein S4, 4-hydroxybenzoate decarboxylase subunit C, and oligopeptide binding protein, were identified, which have the potential to be novel drug target candidates. The Swiss Model server was used to predict the target proteins’ three-dimensional (3D) structure. The molecular docking technique was employed using MOE software for the virtual screening of a library of 15,000 phytochemicals against the interacting residues of the target proteins. Molecular docking experiments were also evaluated using molecular dynamics simulations and the widely used MM-GBSA and MM-PBSA binding free energy techniques. The findings revealed a promising candidate as a novel target against C. pneumonia infections.

Identification and Characterization of Dimorphic Expression of Sex-Related Genes in Rock Bream, a Fish With Multiple Sex Chromosomes.

The rock bream (Oplegnathus fasciatus) is a typical fish with a unique multiple sex chromosome system. In this study, we investigated the gene expression profiling in the gonads and brains of both males and females using RNA-Seq to identify sex-related genes and pathways. In accordance with the dimorphic expression profiles, combined with Gene ontology and KEGG enrichment analyses, a number of potential genes and pathways associated with sex determination were obtained from transcriptional analysis, especially some sex-biased genes and pathways. Next, we selected 18 candidate genes and analyzed their expression in different tissues and developmental stages. We found that the expression levels of Amh, Dmrt1, Sox9, Dmrtb1, and Nanos2 were significantly higher in the testis than those in the ovary or other tissues, whereas the expression levels of ZP4, Bouncer, RNF208, FoxH1, and TOB were significantly higher in the ovary than those in the testis. Furthermore, the expression levels of these genes in different developmental stages of gonads also showed sexually dimorphic patterns, suggesting that they might play important roles during gonadal development. These genes are useful markers for investigating sex determination and differentiation in rock bream. The findings of this study can provide insights into the molecular mechanisms of sex determination and differentiation in fish with multiple sex chromosome systems.

P–546 Exome sequencing and preimplantation genetic testing for unexplained recurrent fetal malformations

Abstract Study question Could patient suffering unexplained recurrent fetal malformations be benefit of PGT-M by exome sequencing mutations identification? Summary answer Patients suffering unexplained recurrent fetal malformations could be benefit of the use of exome sequencing in combination to PGT-M to have a healthy live birth. What is known already Fetal malformations account for approximately 3% of live births and causes include: chromosomal abnormalities, exposure to toxic substances or teratogens and infections. Recently, studies have shown that several monogenic diseases are linked to fetal abnormalities. However, because of the large number of potential genes, genetic testing is challenging. Exome sequencing is widely used to detect genetic mutations and has emerged as a useful tool for finding the genetic cause of fetal abnormalities. The aim of this study was to show how exome sequencing in patients suffering unexplained recurrent fetal malformations in combination to PGT-M could lead to successful healthy newborn. Study design, size, duration Case report of a non-consanguineous couple with unexplained, recurrent fetal malformations. Couple were recruited during clinical consultation for unexplained recurrent fetal malformations at a private reproductive medicine clinic. The couple had two malformed fetus with the same congenital abnormalities: hydrocephalus, cerebellar vermis agenesis, cerebellar hypoplasia and enlarged cisterna magna. Patients signed written informed consent regarding to exome testing. For fetal sample, informed consent was obtained from parents. Participants/materials, setting, methods Sample of the affected fetus were provided. Parental genomic DNA was extracted from peripheral blood. Exome sequencing was performed using TrusightOne (Illumina®). FASTAQ data were processed through BWA and GATK algorithm. VCF files were analysed using Variant Interpreter software. After genetic counselling, PGT-M was performed using linkage polymorphic markers analysis and mutation sequencing. Embryo biopsy was carried at blastocyst stage. Embryos were vitrified and one healthy embryo was thaw and transfer in a subsequent cycle. Main results and the role of chance An homozygous novel pathogenic mutation c.641 C>T (p.Ala214Val) in FVLCR2 gene was found. The parents were heterozygous carriers revealing that the detected variant follow an autosomal recessive pattern. The FLVCR2 (14q24.3) gene encodes a transmembrane protein that belongs to the major facilitator superfamily of secondary carriers that transport small solutes in response to chemiosmosis ion gradients, such as calcium. Mutations in this gene are related to fetal central nervous system defects. This disorder is diagnosed prenatally and is lethal. PGT-M was recommended during genetic counselling. After control ovarian stimulation 14 oocytes were retrieved and finally 4 embryos were suitable for embryo biopsy at blastocyst stage. One embryo was diagnosed as healthy, two affected and one heterozygous carrier. The healthy embryo was thaw and transferred and a healthy male baby was born. Limitations, reasons for caution Exome sequencing has technical limitations: only covers mutations in coding regions and does not cover noncoding regions of the genome. It also cannot reliably detect copy-number variants at single gene level. Wider implications of the findings: This study offers strong evidence of exome-sequencing as a new diagnostic strategy and powerful tool discovering the underlying etiology of recurrent fetal malformations and identifying new genes important for human development. Using this strategy in combination with PGT-M, clinicians can help couples with recurrent fetal malformations to have healthy newborns. Trial registration number Not applicable

Transcriptome profiling reveals key genes in regulation of the tepal trichome development in Lilium pumilum D.C.

A number of potential genes and pathways involved in tepal trichome development were identified in a natural lily mutant by transcriptome analysis and were confirmed with trichome and trichomeless species. Trichome is a specialized structure found on the surface of the plant with an important function in survival against abiotic and biotic stress. It is also an important economic trait in crop breeding. Extensive research has investigated the foliar trichome in model plants (Arabidopsis and tomato). However, the developmental mechanism of tepal trichome remains elusive. Lilium pumilum is an edible ornamental bulb and a good breeding parent possessing cold and salt-alkali resistance. Here, we found a natural mutant of Lilium pumilum grown on a highland whose tepals are covered by trichomes. Our data indicate that trichomes of the mutant are multicellular and branchless. Notably, stomata are also developed on the tepal of the mutant as well, suggesting there may be a correlation between trichome and stomata regulation. Furthermore, we isolated 27 differentially expressed genes (DEGs) by comparing the transcriptome profiling between the natural mutant and the wild type. These 27 genes belong to 4 groups: epidermal cell cycle and division, trichome morphogenesis, stress response, and transcription factors. Quantitative real-time PCR in Lilium pumilum (natural mutant and the wild type) and other lily species (Lilium leichtlinii var. maximowiczii/trichome; Lilium davidii var. willmottiae/, trichomeless) confirmed the validation of RNA-seq data and identified several trichome-related genes.

Fine mapping of a distal chromosome 4 QTL affecting growth and muscle mass in a chicken advanced intercross line

In our previous research, QTL analysis in an F2 cross between the inbred New Hampshire (NHI) and White Leghorn (WL77) lines revealed a growth QTL in the distal part of chromosome 4. To physically reduce the chromosomal interval and the number of potential candidate genes, we performed fine mapping using individuals of generations F10 , F11 and F12 in an advanced intercross line that had been established from the initial F2 mapping population. Using nine single nucleotide polymorphism (SNP) markers within the QTL region for an association analysis with several growth traits from hatch to 20weeks and body composition traits at 20weeks, we could reduce the confidence interval from 26.9 to 3.4Mb. Within the fine mapped region, markers rs14490774, rs314961352 and rs318175270 were in full linkage disequilibrium (D'=1.0) and showed the strongest effect on growth and muscle mass (LOD≥4.00). This reduced region contains 30 genes, compared to 292 genes in the original region. Chicken 60K and 600K SNP chips combined with DNA sequencing of the parental lines were used to call mutations in the reduced region. In the narrowed-down region, 489 sequence variants were detected between NHI and WL77. The most deleterious variants are a missense variant in ADGRA3 (SIFT=0.02) and a frameshift deletion in the functional unknown gene ENSGALG00000014401 in NHI chicken. In addition, five synonymous variants were discovered in genes PPARGC1A, ADGRA3, PACRGL, SLIT2 and FAM184B. In our study, the confidence interval and the number of potential genes could be reduced 8- and 10- fold respectively. Further research will focus on functional effects of mutant genes.

Towards computational improvement of DNA database indexing and short DNA query searching

In order to facilitate and speed up the search of massive DNA databases, the database is indexed at the beginning, employing a mapping function. By searching through the indexed data structure, exact query hits can be identified. If the database is searched against an annotated DNA query, such as a known promoter consensus sequence, then the starting locations and the number of potential genes can be determined. This is particularly relevant if unannotated DNA sequences have to be functionally annotated. However, indexing a massive DNA database and searching an indexed data structure with millions of entries is a time-demanding process. In this paper, we propose a fast DNA database indexing and searching approach, identifying all query hits in the database, without having to examine all entries in the indexed data structure, limiting the maximum length of a query that can be searched against the database. By applying the proposed indexing equation, the whole human genome could be indexed in 10 hours on a personal computer, under the assumption that there is enough RAM to store the indexed data structure. Analysing the methodology proposed by Reneker, we observed that hits at starting positions are not reported, if the database is searched against a query shorter than nucleotides, such that is the length of the DNA database words being mapped and is the length of the query. A solution of this drawback is also presented.