Pathogenic predictions of non-synonymous variants and their impacts: A computational assessment of ARHGEF6 gene

Introduction: ARHGEF6, a key member and activator of RhoGTPases family that is involved in G-Protein Coupled receptor (GPCR) pathway and stimulate Rho dependent signals in the brain, and mutations in this gene can cause intellectual disability (ID) in Human. Therefore, we aimed to study the consequences of ARHGEF6 non-synonymous mutations by using advanced computational methods.Methods: Classification of the genetic mutations in ARHGEF6 gene was performed according to Ensembl Genome Database and data mining was done using ensemble tools. The functional and disease effect of missense mutations, and pathogenic characteristics of amino acid substitutions of ARHGEF6 were analyzed using eleven diversified computational tools and servers.Results: Overall, 47 ARHGEF6 non-synonymous (NS) variants were predicted to be deleterious by SIFT, Polyphen2 and PROVEAN scores. Above that, SNPs&GO and PhD SNP were further graded 21 customarily pathogenic NS-variants. Protein stability analysis resulted in the significant change in terms of △△G of most identified NS-variants, except K609I. Seven variants were analyzed to be located on most potential domain RhoGEF/DH, whereas the remaining 14 were distributed on CH, SH3, PH and BP domains. Furthermore, pathogenic effects of mutations on protein was presented with different parameters using MutPred2 and PROJECT HOPE. Additionally, STRING network data predicted GIT2 and PARVB as most interacted partners of ARHGEF6.Conclusion: These findings can be supportive of genotype-phenotype research as well as the development in pharmacogenetics studies. Finally, this study revealed a significance of computational methods to figure out highly pathogenic genomic variants linked with the structural and functional relationship of ARHGEF6 protein.Keywords: Computational methods, ARHGEF6, Intellectual disability, Missense mutatio

Azoospermia factor C subregion of the Y chromosome

The azoospermia factor (AZF) region on the Y chromosome consists of genes required for spermatogenesis. Among the three subregions, the AZFc subregion located at the distal portion of AZF is the driver for genetic variation in Y chromosome. The candidate gene of AZFc is known as deleted in azoospermia gene, which is studied with interest because it is involved in germ cell development and most frequently deleted genes leading to oligozoospermia and azoospermia. Recently, two partial deletions in AZFc gr/gr and b2/b3 are characterized at the molecular level which showed homologous recombination between amplicons, affecting spermatogenesis process. There are novel methods and commercially available kits for accurate screening and characterization of microdeletions. It is important to detect the AZFc microdeletions through genetic screening and counseling those infertile men who planned to avail assisted reproduction techniques such as undergoing intracytoplasmic sperm injection or in vitro fertilization

Anticariogenic and phytochemical evaluation of Eucalyptus globules Labill.

AbstractIn the present study, in vitro anticariogenic potential of ethyl acetate, hexane and methanol and aqueous extracts of plant leaves of Eucalyptus globules Labill. were evaluated by using four cariogenic bacteria, Lactobacillus acidophilus, Lactobacillus casei, Staphylococcus aureus and Streptococcus mutans. Agar well diffusion method and minimum inhibitory concentration (MIC) were used for this purpose. The ethyl acetate extracted fraction of plant leaves showed good inhibitory effects against all selected bacteria. In Eucalyptus globules, hexane and ethyl acetate extracts found highly effective against, Lactobacillus acidophilus with MIC value of 0.031 and 0.062 mg/mL, respectively. Qualitative phytochemical investigation of above extracts showed the presence of alkaloids, phenolic compounds, steroids, cardiac glycosides and terpenes. Based on the MIC value and bioautography, ethyl acetate of plant leaf was selected for further study. Further investigation on the structure elucidation of the bioactive compound using IR, GC-MS and NMR techniques revealed the presence of alpha-farnesene, a sesquiterpene. Eucalyptus globules plant leaf extracts have great potential as anticariogenic agents that may be useful in the treatment of oral disease

Factor XI deficiency in Indian Bos taurus, Bos indicus, Bos taurus x Bos indicus crossbreds and Bubalus bubalis

We investigated the occurrence of Factor XI (FXI) deficiency syndrome in the following Indian dairy animals: Bos taurus Holstein-Friesian and Jersey cattle, Bos indicus Indian cattle breeds, B. taurus x B. indicus crossbreds and the river buffalo Bubalus bubalis. Factor XI deficiency is an autosomal recessive bleeding disorder known to affect Holstein cattle worldwide. A total of 1001 dairy animals, mainly bulls, were genotyped to detect the mutation within exon 12 of the gene encoding for factor XI. Two Holstein bulls were detected as heterozygous (carrier) for FXI deficiency, giving a carrier frequency of 0.6% in Indian Holstein cattle. None of the other cattle or buffalo breeds was found to be a carrier for FXI. Sequence comparison between normal and heterozygous animals revealed that there is a 77 base pair insertion fragment (AT (A)29 TAAAG (A)27 GAATTATTAATTCT) within exon 12 of the FXI gene. Both sequences were submitted to the National Center for Biotechnology Information (NCBI) GenBank and assigned the accession numbers DQ438908 for normal Holstein Friesian animals and DQ438909 for heterozygous Holstein Friesian animals