Microbes use diverse defence strategies that allow them to withstand exposure to a variety of genome invaders such as bacteriophages and plasmids. One such defence strategy is the use of RNA guided endonuclease called CRISPR-associated (Cas) 9 protein. The Cas9 protein, derived from type II CRISPR/Cas system, has been adapted as a versatile tool for genome targeting and engineering due to its simplicity and high efficiency over the earlier tools such as ZFNs and TALENs. With recent advancements, CRISPR/Cas9 technology has emerged as a revolutionary tool for modulating the genome in living cells and inspires innovative translational applications in different fields. In this paper we review the developments and its potential uses in the CRISPR/Cas9 technology as well as recent advancements in genome engineering using CRISPR/Cas9.

Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

Recently, genetic markers rs10503253 and rs2616984 in the CUB and Sushi multiple domains-1 (CSMD1) gene have been reported to be associated with schizophrenia and cognitive functions in genome-wide association studies. We examined the associations of the above SNPs with cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) tool in a cohort of the normal elderly from the Russian population. Significant association of rs2616984 genotypes with the MoCA scores was found using nonparametric analysis. No association of rs10503253 with MoCA scores was observed using both parametric and nonparametric statistics. Significant combined effect of two-locus CSMD1 genotypes on MoCA scores was demonstrated by median test. Allele “A” and genotype “AA” of rs2616984 were significantly associated with the lower MoCA scores in comparison of 1st and 4th quartiles of MoCA total score distribution. The results suggest that genetic variants in CSMD1 gene are likely a part of genetic component of cognitive performance in the elderly.

HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. While the cause remains unclear, evidence suggests that HIV-associated neurocognitive disorders (HAND) may be associated with neurobehavioral dysfunction. Genetic variants have been explored to identify risk markers to determine neuropathogenesis of neurocognitive deterioration. Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life and HIV risk-taking behaviors. Single nucleotide polymorphisms in the SLC6A4, TPH2, and GALM genes may affect the activity of serotonin and increase the risk of HAND. The present study explored the relationship between SLC6A4, TPH2, and GALM genes and neurocognitive impairment in HIV-infected alcohol abusers. A total of 267 individuals were genotyped for polymorphisms in SLC6A4 5-HTTLPR, TPH2 rs4570625, and GALM rs6741892. To assess neurocognitive functions, the Short Category and the Auditory Verbal Learning Tests were used. TPH2 SNP rs4570625 showed a significant association with executive function in African American males (odds ratio 4.8, 95% CI, 1.5–14.8; P = 0.005). Similarly, GALM SNP rs6741892 showed an increased risk with African American males (odds ratio 2.4, 95% CI, 1.2–4.9; P = 0.02). This study suggests that TPH2 rs4570625 and GALM rs6741892 polymorphisms may be risk factors for HAND.

Aging is a complex process characterized by a steady decline in an organism's ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age.

Genetics is a relatively young science compared to many other fields in biology, for example, evolutionary biology or physiology. However, genetics is a central theme in many fields, especially the medical sciences, because genetic studies can provide explanations and may even allow predictions to be made, in the context of a range of biological problems including the field of inherited human disorders. This has become especially important during the last decade as we have entered the “genomic era.” With the dramatic improvement of sequencing technologies and the enormous reduction in the cost of sequencing, biologists are faced with a “data avalanche.” Next generation whole exome or genome sequencing has provided us with an arsenal of tools to study human, animal, and plant genetics. The underlying genetic lesions responsible for Mendelian diseases may now be found and mapped with even a limited number (as few as one) of affected individuals (rare and neglected diseases), with the help of large quantities of “control” genome data such as those emanating from the 1000 Genomes Project. Genomic data analysis may also be useful for the dissection of the genetic mechanisms underlying complex polygenic diseases or in exploring the role of modifiers genes in influencing the age of onset or clinical severity of a given Mendelian disease entity. Although we have acquired new research capabilities, we are also encountering new problems with the analysis of genomic data and the reanalysis of already published (deposited in databases) data. Such problems of genomic data presentation, format, sharing, and reanalysis are now starting to be addressed. This special issue is dedicated to problems of genetics in the genomic era and comprises five articles: three review articles and two research articles. In the first review article, entitled “Unlimited Thirst for Genome Sequencing, Data Interpretation, and Database Usage in Genomic Era: The Road towards Fast-Track Crop Plant Improvement,” A. P. Dhanapal and M. Govindaraj discuss the use of crop plant databases in advancing research in the genomic era. The major focus of this review is to provide knowledge on platforms for comparative genomics of agriculturally important crop plants with industrial and environmental significance. Recent advances in sequencing and resequencing of plant genomes have potentiated new analyses of genomic variation and gene function. Genetic variation databases could facilitate research that helps to improve the efficiency of plant breeding programs. This review should aid researchers in the plant science research community by providing information on available databases and platforms for genome-based analyses that help to link model systems with other plants in the genomics context. This is a timely review which highlights the recent finding of frequent gene and whole genome duplication events. Many unresolved questions however remain regarding the number and timing of such events in plant evolution. Gene duplication is a key mechanism of genomic change in evolution. I. B. Rogozin discusses recent analyses of the “ortholog conjecture” (OC) hypothesis. Under the OC hypothesis, which is central to the functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. A recent study found a greater functional similarity, in terms of gene ontology (GO) annotations and expression profiles, among within-species paralogs as compared to orthologs. These findings have suggested that the functional similarity of homologous genes is primarily determined by the cellular context of those genes, rather than their evolutionary history. Subsequent studies have suggested that the OC hypothesis appears to be generally valid but that a comprehensive picture of the evolution of gene expression requires the incorporation of lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication may be most parsimoniously explained by the duplication-degeneration-complementation model combined with selection for gene dosage. E. Poliakov et al.'s research paper reinforces the central importance of gene expression. Some ninety years on from the first articulation of the Warburg theory of cancer cell origin, the question of altered metabolism in cancer is again assuming a central role. Analyses of signaling pathways and oncogenes in different types of cancer have been the focus of research for several decades. Now, empowered by a wealth of knowledge about tumor suppressor genes, oncogenes, and signaling pathways, the reprogramming of cellular metabolism (e.g., increased glycolysis to respiration ratio in cancer cells) has reemerged as a key step in cancer progression. To obtain a general picture of cancer metabolism and to analyze the level of expression of various genes encoding proteins including metabolic enzymes across various cancers, E. Poliakov et al. employed dbEST and Unigene data. With the appearance of abundant RNA-seq cancer data, it is interesting to ascertain if dbEST-based conclusions will hold. The authors delineated a list of genes that are overexpressed in most types of cancer. They also grouped overexpressed enzymes into KEGG pathways and analyzed adjacent pathways to describe the enzymatic reactions that take place in cancer cells thereby identifying major players in the cancer protein machinery. Glycolysis/gluconeogenesis, oxidative phosphorylation, and pyruvate metabolism appear to be the most abundant pathways although several other pathways are enriched in genes from the list. Ubiquitously overexpressed genes could be marked as nonspecific cancer-associated genes when analyzing genes that are overexpressed in certain types of cancer. Thus, the list of overexpressed genes is likely to be a useful tool for systems biology approaches to cancer research. D. Hmida-Ben Brahim et al. discuss Huntington disease (HD) (an autosomal dominant neurodegenerative disorder). The causative mutation is an expansion of more than 36 CAG repeats in the first exon of the HTT (IT15) gene. Many studies have shown that the HTT gene interacts with several modifier genes to regulate the age at onset of HD. Their study aims to investigate the involvement of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients. The authors establish a correlation between these modifier genes and the age of onset of this disease. Their results demonstrate a specific effect of modifier genes in each population. Despite the small number of studied patients, this report constitutes the first North African study of Huntington disease patients. This special issue is concluded by an article by M. Srinivasan et al. that discusses the importance of genetic diversity assessment in crop plants and its recent advances. The importance of plant genetic diversity is now being widely recognized by agricultural scientists. This paper comprehensively reviews four important areas: (i) the significance of plant genetic diversity (PGD); (ii) the risk associated with the narrowing down of the genetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods in both the pregenomic and genomic eras; and (iv) the tools now available for PGD analysis in the postgenomic era. This review describes the new methods and technology for the improved and rapid assessment of the genetic diversity of crops and for the utilization of germplasm from gene-banks in their applied breeding programs. Since plant breeding research and cultivar development are integral components of improving food production, the availability of and access to diverse genetic stocks will help make the global food production network become more sustainable. The pros and cons of the use of basic and advanced statistical tools available for measuring genetic diversity are discussed. We have no doubt that there are many topics that remain uncovered in this special issue. However, we hope that the approaches described here will become widely used by the scientific community. Eugenia Poliakov David N. Cooper Elena I. Stepchenkova Igor B. Rogozin

The importance of plant genetic diversity (PGD) is now being recognized as a specific area since explodingpopulation with urbanization and decreasing cultivable lands are the critical factors contributing to food insecurity in developing world.Agricultural scientists realized that PGD can be captured and stored in the form of plant genetic resources(PGR) such as gene bank, DNA library, and so forth, in the biorepository which preserve genetic material for long period. However, conserved PGR must be utilized for crop improvement in order to meet future global challenges in relation to foodand nutritional security. This paper comprehensively reviews four important areas; (i) the significance of plant genetic diversity (PGD) and PGR especiallyon agriculturally important crops (mostly field crops); (ii) risk associated with narrowing thegenetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods inpregenomic and genomic era; and (iv) modern tools available for PGD analysis in postgenomic era. This discussionbenefits the plant scientist community in order to use the new methods and technology for better and rapid assessment,for utilization of germplasm from gene banks to their applied breeding programs. With the advent of new biotechnologicaltechniques, this process of genetic manipulation is now being accelerated and carried out with more precision (neglectingenvironmental effects) and fast-track manner than the classical breeding techniques. It is also to note that gene banks lookinto several issues in order to improve levels of germplasm distribution and its utilization, duplication of plant identity, andaccess to database, for prebreeding activities. Since plant breeding research and cultivar development are integral componentsof improving food production, therefore, availability of and access to diverse genetic sources will ensure that the global foodproduction network becomes more sustainable. The pros and cons of the basic and advanced statistical tools available formeasuring genetic diversity are briefly discussed and their source links (mostly) were provided to get easy access; thus,it improves the understanding of tools and its practical applicability to the researchers.

The identities of genes that underlie population variation in adipose tissue development in farm animals are poorly understood. Previous studies in our laboratory have suggested that increased fat tissue involves the expression modulation of an array of genes in broiler chickens. Of special interest are eight genes, FGFR3, EPHB2, IGFBP2, GREM1, TNC, COL3A1, ACBD7, and SCD. To understand their expression regulation and response to dietary manipulation, we investigated their mRNA levels after dietary manipulation during early development. Chickens were fed either a recommended standard or a high caloric diet from hatch to eight weeks of age (WOA). The high caloric diet markedly affected bodyweight of the broiler birds. mRNA levels of the eight genes in the abdominal adipose tissue were assayed at 2, 4, 6, and 8 WOA using RT-qPCR. Results indicate that (1) FGFR3 mRNA level was affected significantly by diet, age, and diet:age interaction; (2) COL3A mRNA level was repressed by high caloric diet; (3) mRNA levels of EPHB2, ACBD7, and SCD were affected by age; (4) mRNA level of TNC was modulated by age:diet interaction; (5) changes in GREM1 and IGFBP2 mRNA levels were not statistically different.

Chemoresistance to conventional cytotoxic drugs may occur in any type of cancer and this can either be inherent or develop through time. Studies have linked this acquired resistance to the abnormal expression of microRNAs (miRNAs) that normally silence genes. At abnormal levels, miRNAs can either gain ability to silence tumour suppressor genes or else lose ability to silence oncogenes. miRNAs can also affect pathways that are involved in drug metabolism, such as drug efflux pumps, resulting in a resistant phenotype. The scope of this review is to provide an introspective analysis on the specific niches of breast carcinoma and neuroblastoma research.