Genetics in the Third Millennium
Volume:8 Issue: 3, 2011

Several reports from different regions of Iran indicate the importance of 35delG mutation in GJB2 gene. In the present study, mutation frequency of 35delG in the population of Autosomal Recessive Non-Syndromic Hearing Loss (ARNSHL) was investigated in the province of Isfahan. Sixty-three Isfahani unrelated patients with ARNSHL were included in the study. Patients were screened for the 35delG mutation in GJB2 using allele refraction mutation system/PCR (ARMS/PCR) followed by sequencing. Of 126 studied chromosomes, 39 (31.0%) were found to be positive for 35delG mutation. Because 35delG mutation shows a relatively high frequency in most parts of Iran, the population of Isfahan could be considered as populations with a high frequency of the mutation.

Hallervorden-Spatz Syndrome (HSS), which is also known as Neurodegeneration with Brain Iron Accumulation (NBIA), is a rare neurodegenerative disease which begins in childhood, adolescence or older ages. The clinical manifestations include extrapyramidal symptoms, cognitive impairment, optic atrophy and retinitis pigmentosa. Genetic studies have revealed a mutation in the panthotenate kinase 2 (PANK2) gene on chromosome 20p13 and the term Pantothenate Kinase Associated Neurodegeneration (PKAN) has also been suggested for these patients. In this review, clinical manifestations, genetic findings, radiologic findings and treatment of this syndrome will be discussed.

X-linked immunodeficiency with hyper-IgM (XHIGM or HIGM1) is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for CD40 ligand (CD40L, also known as gp39, TNFSF5 and CD154). CD40L is expressed on activated CD4+T cells and interacts with CD40 on the surface of B cells. This interaction induces B cells to undergo immunoglobulin (Ig) class-switching from IgM to IgG, IgA, and IgE. Patients with XHIGM exhibit profoundly depressed B-cell activation, fail to form germinal centers, have markedly reduced levels of IgG, IgA, and IgE but have normal or elevated levels of IgM. Because CD40L is required in the functional maturation of T lymphocytes and macrophages, patients with XHIGM also have a variable defect in T-lymphocyte and macrophage effector function. The range of clinical findings of XHIGM varies, even within the same family. Patients with XHIGM have increased susceptibility to infection with a wide variety of bacteria, viruses, fungi, and parasites. XHIGM usually presents in infancy with recurrent upper and lower respiratory tract bacterial infections, opportunistic infections, and recurrent or protracted diarrhea caused by Cryptosporidium parvum which is associated with failure to thrive. Neutropenia, thrombocytopenia, and anemia are common. Malignancies, Significant neurologic complications, oral ulcers, autoimmune and/or inflammatory disorders, such as sclerosing cholangitis, liver diseases including hepatitis, primary cirrhosis and carcinomas and tumors of the gastrointestinal tract have been reported.

RNA silencing is regarded as a strong defensive mechanism against plant viruses. RNA silencing acts against plant viruses and reduces virus concentration and leaf symptoms. Since RNA silencing is a key route of defense against plant viruses, many plant viruses evolve to resist and survive this system. Some viruses encode proteins that suppress RNA silencing created by siRNA and miRNA and increase virus concentration. Most plant viruses encode suppressors of RNA silencing which include some viral proteins that interact with various parts of RNA silencing at different stages. Coevolution of plant viruses and plants in the long time results in suppression of RNA silencing by viral suppressors. However, more knowledge regarding these routes and the role of viral suppression proteins facilitate our understanding of plant resistance against viruses and production of transgenic plants which are resistant to viruses.

Brain memory storage and information processing occurs through changes in synaptic connections between neurons or synaptic plasticity. In experimental models of synaptic plasticity such as LTP, stabilization of these changes requires de novo protein synthesis. Immediately after stimulations that induce LTP or behavioral experiments which contribute to Long Term Memory (LTM) formation, Immediate-Early Genes are induced in hippocampal neurons; among neuronal activity dependent IEGs, Arc is of particular importance. Arc is robustly induced by plasticity-producing stimulation and is specifically targeted to stimulated synaptic areas. It also plays a critical role in the maintenance of long term potentiation and in memory consolidation processes. Inhibition of Arc protein expression in the rat hippocampus, through ODNs infusion, impairs maintenance of LTP and consolidation of LTM. Thus, Arc appears to play a fundamental role in stabilization of activity-dependent hippocampal plasticity. In this paper, the role of Arc in memory formation is discussed.

In the nature, organisms encounter different pathogens and microorganisms and in order to survive, they need to recognize and fight them. Pathogens include compounds in the structure of an organism such as lipopolysaccharides, nucleic acid and lipoproteins that can be recognized by the immune system. These compounds are known as Pathogen-Associated Molecular Patterns (PAMPs). A group of cell receptors that are named Toll-Like Receptors (TLR) recognize PAMPs. Today, at least 14 receptors in this family are discovered and each one is responsible for recognizing PAMPs. TLR9, one of these receptors, recognizes the DNA of bacteria and viruses. Stimulation of this receptor releases immune cells and activates both innate and adaptive immune systems. Sequences containing unmethylated CPG dinucleotides activate Toll-like Receptor 9 (TLR9). Scientists make synthetic forms of CPG sequences and use them in many immune researches like vaccine adjuvants. In addition, CPG dinucleotides can be used to stimulate the response of T lynphocytes against tumors, regulate cellular immune responses and activate humoral immunity.

Zellweger Syndrome is one of peroxisomal disorders with autosomal recessive inheritance. The main characteristic feature are growth and developmental retardation, high forehead, cloudy cornea, cataract, depressed nasal bridge, very large fontanels, low set ears, rhizomelia, severe hypotonia. We are reporting a 2 months girl with failure to thrive, severe hypotonia, large fontanels and rhizomelia. She was first child of related parents. We believed that the patient suffered from Zellweger syndrome, which documented with metabolic investigations, that showed low plasmalogen level.

Essential hypertension (EH) accounts for 90-95% of hypertension cases. EH, as a progressive cardiovascular syndrome arising from complex and interrelated etiologies, results from combined and interactive effects of genetic and environmental factors. The objective was to investigate the ACE I/D and GNB3 C825T polymorphisms and both genotypes combined with seeking gene-gene interactions to further clarify the role of these genes in the pathogenesis of EH. Eight hundred and ten consecutive ethnic-matched unrelated north Indian subjects, 360 healthy controls from the general population and 450 patients, were enrolled. Plasma renin activity and plasma aldosterone concentration were measured. The variant GNB3 C825T was typed by SNaPshot and analyzed on Genetic Analyzer and GeneScan. Genotypes-combinations and gene-gene interactions were also performed. We found that the plasma ACE levels were higher in hypertensive patients than healthy controls. The ACE DD genotype was associated with the highest circulating ACE levels, ID heterozygotes were associated with intermediate and II heterozygotes with the lowest ACE levels in either patients or controls. Our data suggested a significant interaction between the GNB3 825T allele and the ACE D allele in CVD and likely EH. The patients bearing (DD + CT or ID + TT) and (DD + TT) combinations, respectively, showed a significant association with EH. Logistic regression revealed a 2.7-fold greater risk of hypertension associated with the (DD + CT or ID + TT) combination, and likewise, a 6.4-fold greater chance of hypertension was associated with the (DD + TT) combination. GNB3 C825T and ACE I/D gene-gene interaction in our study revealed that (DD + CT or ID + TT) and (DD + TT) combinations were significantly associated with EH and higher risk of hypertension, respectively. In a synergistic gene-to-gene interaction among the three polymorphisms, genotypic combinations containing three and/or four unfavorable alleles had a significantly increased chance of EH. These results strengthen the hypothesis that genotypic combinations are more important than a single gene polymorphism.