Indian Journal of Genetics and Molecular Research

 This is a well-established fact about genetic code is that code is universal and consists of codons set in the customary typical tabulation that on the other hand go around as greatly non-random. Various communally allied theories were specified concerning the perceptions about the origin and evolution of the genetic code. There are not many accomplishments in the short past account of molecular biology which had an intense impact on the progression of science and at the same time are stalwartly embossed in the civic insight. Decoding and interpretation of Genetic code is definitely one of such event. The genetic code is vital to each and every form of existence and is of elementary significance to the entire biology. Earlier it was a conviction that protein is accountable for transferring the genetic information from one to the other generation. All concepts and theories in nutshell recommended that the customary code might have no unique features but was preset simply because each and every existing forms of life have a common predecessor, by way of consequent alterations to the code, irrelevant of the lethal effects of codon relocations. A genuine and factual appreciation of the origin and evolution of this genetic code can be accomplished only in juxtaposition with a plausible setting for the evolution of the theories of coding and translation coordination. Here the discourse of the perceptions of various workers and evolution of the genetic code with time is discussed.

Keywords: Genetic Code; Evolution; Codons

 Chromosome 18 represents approximately 2.5% of the total DNA in cells and contains 200 to 300 genes that code for proteins essential for a variety of functions in the body. Partial deletions of the p and q arms can result in ring formation. Ring chromosome 18 is one of the rare structural chromosome abnormalities. This aberration can cause varied phenotypic manifestations ultimately leading to a suboptimal loss of body function. Structural abnormalities affect genes of the defunct part of the chromosome. Subsequent loss of protein translation leads to various genetic abnormalities, depending on the location and extent of the genes deleted during formation of the ring. Hence, there are various manifestations of this disorder. Most of the children with ring chromosomes show a failure to thrive beyond the extent expected from their chromosomal imbalances. The phenotypic diversity observed in Ring 18 is described. Chromosome abnormalities including ring 18 detected in our laboratory in a child with metabolic leukodystrophy are illustrated. The availability of preimplantation genetic diagnosis (PGD) in India and its benefits are highlighted.

Keywords: Ring Chromosome 18; Telomeres; Leukodystrophy; Microarray; NGS; FISH; PGD.

 Risperidone is metabolized by cytochrome P4502D6 (CYP2D6) to its active metabolite, 9- hydroxyrisperidone. CYP2D6 genes encoding this enzyme are polymorphically expressed and most of the variants result in decreased substrate metabolism. The influence of CYP2D6*10 polymorphism on risperidone and 9-hydroxyrisperidone plasma levels, metabolic ratio and dose adjusted active moiety in Indian Schizophrenic patients were assessed. Also, the prevalence of CYP2D6*10 in normal healthy volunteers residing in Maharashtra were determined. The study was initiated following Institutional Ethics Committee approval and written informed consent from participants. Seventy two schizophrenic patients and One hundred and eleven healthy volunteers were genotyped for CYP2D6*10 by PCR-RFLP method. Risperidone and 9-hydroxyrisperidonelevels were estimated in patients by HPLC. Clinical assessment of patients was done using PANSS score. Genotype frequencies were calculated using Hardy-Weinberg equilibrium. Differences in (corrected dose) C/Ds plasma drug, Metabolic Ratio, PANSS score between different genotypes was analyzed using one way ANOVA for normally distributed data and KruskalWallis test in case of non-normally distributed. Pearson’s correlation was used to examine the relationship between drug levels and dosage. Frequency of T allele observed was 16% in controls and 19% in schizophrenic patients. Poor Metabolizers had significantly higher levels of risperidone C/D and Metabolic Ratio than homozygous Extensive Metabolizers and Intermediate metabolizers. No statistically significant correlation was found between PANSS score and plasma levels. A strong correlation was however observed between the drug levels and administered dose. Our findings suggest that CYP2D6 may be a useful determinant of risperidone & 9-OH-risperidone drug levels and their Metabolic Ratio.

Keywords: CYP2D6; Genotype-Phenotype Correlation; Indian Population; Risperidone; 9-OH Risperidone; Schizophrenia.

 Meiotic division requires pairing of homologous chromosomes for normal segregation, recombination, and production of haploid gametes. Early in meiotic prophase, chromosomes begin pairing off from the telomeric ends toward the centromere, irrespective of chromosome morphology. Since synaptonemal complex formation during zygotene/early pachytene begins at the telomeres, we hypothesized that in some infertile human males telomeric chromosomal DNA may be constitutionally reduced and, therefore, insufficient to initiate homologous synapsis, resulting in asynaptic meiosis and azoospermic infertility. To test this hypothesis, we measured and compared percent telomeric DNA in peripheral blood lymphocytes (PBLs) and testicular biopsies from infertile males (cases) and agematched normal fertile males (controls). Quantitative fluorescence in situ hybridization (QFISH) revealed that cases had significantly less telomeric DNA than did controls (P < 0.001; P = 0.002 respectively). In addition, in experiments with mouse testes exposed to the telomerase-inhibiting and sterility-inducing drug, cytarabine in vivo, silver staining and analysis of synaptonemal complexes showed that homologous chromosome pairing was prevented due to the loss of telomeric DNA. Taken together, these observations indicate that constitutionally reduced amounts of telomeric DNA in somatic and germ cells may be a crucial determinant in human male sterility.

Keywords: Homologous Pairing; Infertility; Pachytene; Synaptonemal Complex; Telomeric DNA.