Genetics in the Third Millennium
Volume:11 Issue: 2, 2013

People are usually susceptible to the carcinogenic and mutagenic aromatic amines through smoking and polluted environments. These chemicals participate to make DNA adducts and to cause DNA damages. DNA repaired enzymes are associated with maintaining the integrity of damaged DNA and prevention of cells'' neoplastic transformation. NER repaired system is one of the major pathways of DNA repair with the widespread function; Therefore، XPD Lys751Gln polymorphism related to this repaired system and according to the lung cancer risk، has been studied in different age and sex groups extensively. In this study، the lung cancer risk in different age and sex groups related to the mentioned polymorphism was investigated in Iranian population. Then، the results were analyzed by SPSS software version 16. The performed analyses through frequency tables and correlation coefficient with %95 confidence indicated that XPD genotypes have significant relationship with sex and lung cancer risk، in the other hands lung cancer risk in above 50 years old person with Lys751Gln polymorphism observed dominantly. Also، mentioned polymorphism was seen in men more than women.

Taking its toll as 250000 deaths of men around the world، prostate cancer has been one of the main causes of cancer-related death world-wide. Although prostate-specific antigen)PSA (has long been used as a biomarker for the management of prostate cancer، attempts have recently been shifted to try to find some other markers، largely as a result of PSA limitations as a reliable marker. Two remarkable examples of these biomarkers are NKX3. 1 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) genes. Here، in line with earlier studies that have drawn an analogy between the concurrent expression of PTEN and NKX3. 1 genes، we decided to evaluate and make a relation between the expression levels of these genes on mRNA level، using quantitative Real-Time PCR. Based on our results، the expression rate of NKX3. 1 and PTEN decreased to 0. 155 and 0. 003، respectively (P = 0. 000). We concluded that the association between the down regulation of PTEN and NKX3. 1 genes is correlated with tumor progression. This result might highlight the interaction between the proteins encoded by these genes. Furthermore، this finding might be exploited as a prospective biomarker for the development of innovative diagnostic and therapeutic techniques.

Shigella dysenteriae type 1 is a major cause of diarrhea in humans and also Cholera is a potentially fatal bacterial infection that causes severe diarrhea and dehydration. Thus، producing a vaccine against these bacteria seems to be very useful. The best methods for making a vaccine against these two diseases is enterotoxin B subunit in both of them، which names StxB (for Shigella dysenteriae type 1) and CtxB (for Vibrio cholera). These two parts connect the toxic subunit (subunit A) to cell surface receptors of these two toxins in the intestinal epithelium. Shigella IpaD proteins can also be a good target to produce a vaccine against Shigella. IpaD is required for pore formation، bacterial invasion، and virulence. IpaD is responsible for insertion of IpaB/IpaC pores into target cell membranes. Consequently، producing antibodies against IpaD can prevent shigella from making pores in cells and after immune response against them antibodies can prevent the entry of the toxin into the cells. CtxB is highly effective mucosal adjuvant triggering strong protective immunity to unrelated antigens and can be used to prevent or treat inflammatory diseases. Therefore، fusion of these three genes to produce vaccine has two main important benefits: i) by using of adjuvant properties of CtxB، immunization against IpaD and StxB would increase; ii) this vaccine could be effective against both of these bacteria. The study compares all the possible combinations of binary and ternary proteins with various properties by the use of bioinformatics software such as Modeller، ProtParam and psipred and identifies CtxB-StxB-IpaD as the best possible combination.

Diabetes is a multifactorial disorder and many genes related to diabetes are detected. APOA1 is located on chromosome 11 and has role in the lipids metabolism. There is close relationship between lipids and carbohydrate metabolism. Therefore it is a possibility of relationship between APOA1 gene and carbohydrate metabolism. In this case control study the incidence of APOA1 polymorphism in patients with type 2 diabetes were investigated. In total 200 diabetic patients referred to Yazd Diabetes Research Center were investigated. Blood sample of these patients and 200 individuals without diabetes as controls were collected. DNA was extracted and then PCR-RFLP method was used. The genotype M1+/+ was detected in 57. 6% of cases and 58. 7% of controls، while genotype M1+/- was detected in 36. 7% of cases and 34. 2% of controls and genotype M1-/- in 5. 6% of cases and 7. 1% of controls. Regarding M2 genotype، M2+/- and M2-/- were reported together and the results indicated that the rate of M2+/+ was 93. 8% in patients and 94% in controls while the rate of the other two genotype were 6. 2% in patients and 6% in controls. Our study showed that there is no significant difference in the rate of APOA1 gene polymorphism between diabetic patients and control group. This indicates that there is no relationship between APOA1 polymorphism and diabetes. Therefore it seems that the major role of APOA1 is in lipid metabolism and not carbohydrate metabolism.

The aim of this study was to evaluate the concordance of sex chromatin with karyotype. According to the Lyon’s hypothesis، one X chromosome is enough for the metabolism of the somatic cells. Therefore، all X chromosomes but one become inactivated and form the sex chromatin. In addition to karyotyping، sex chromatin was evaluated in all patients who were investigated for chromosomal abnormality، infertility، and abortion. Among 88359 cases of peripheral blood karyotype between 1983 and 2013 (75 months and 12 days)، 9450 were also investigated for sex chromatin out of whom 5374 (57%) were positive and 4076 (43%) were negative for sex chromatin. In this study، the results of sex chromatin are reported as percentage، and not as positive or negative. Comparison of cytogenetic and sex chromatin findings showed that: 1- The karyotype was concordant with sex chromatin findings in individuals whose sex chromatin was 20% or more. 2- Positive sex chromatin was divided into eight groups based on percentage as follows: 1-4%، 5-9%، 10-14%، 15-19%، 20-24%، 25-29%، 30-34%، and 35-40%. These groups were then compared with the patient’s karyotypes. 3- In the above-mentioned groups، similar to the first group (except for cases with i(Xq) and X ring) the percentage of the sex chromatin was concordant with the patients’ karyotypes and the percentage of its types. 4- Barr bodies were thicker than normal in cases with isochromosome X mosaicism i (Xq) and thinner than usual in X ring. Barr bodies did not have any concordance with the percentage of the karyotype structure. 5- Solutions that are used for careful evaluation of the sex chromatin should stain the contents of the nucleus، leaving the cytoplasm unstained. 6- We believe that evaluation of the sex chromatin in cases who are suspicious of chromosomal abnormalities is a rapid، safe، and easy method for the investigation of the normal karyotype structure، mosaicism، and abnormalities of the X chromosome. It can also confirm the number and structure of the X chromosomes.

syndrome is a very rare hereditary lethal skeletal dysplasia. There are few reports of milder phenotypes that patients were survived till late childhood. Radiologic investigations showed increased bone density and osteosclerosis. The increased density of bones in head and face causes a characteristic dysmorphic features that includes: prominent and narrow forehead، proptosis، small hypoplstic nose with depressed nasal bridge، mid-face hypoplasia، triangular moth، coanal atresia، and intracranial cerebral calsification. Osteosclerosis is severe enough that would be mistaken with osteopetrosis. Raine syndrome is a hereditary autosomal recessive disease. The cause of it is a homozygous or compound heterozygous mutation in the FAM20C gene. The gene encodes a phosphorylase-kinase which is responsible for biomineralization of skeleton. Here we report a typical patient of this syndrome from Iran، and to our knowledge this is the first confirmed one in our population. Molecular analysis showed a homozygous novel mutation in the FAM20C gene. This patient is the 17th reported case in the relevant literature.

T cell acute lymphoblastic leukemia (T-ALL) is one of the most frequent malignancies related to T cells which usually considers as an invasive tumor. This cancer is caused by oncogenes activation or tumor suppressor deactivation pathways. Investigating of these pathways can introduce new therapeutic targets. In this review article the most frequent signaling pathways in T-ALL including Notch، PI3k/Akt، MAPKs، Jak/SATA، NF-kB and calcineurin/NFAT are explained. In addition، several mechanisms by which leukemia medications may operate، are discussed.

The majority of mitochondrial proteins are synthesized in the cytosol. These proteins contain specific indication signals that define targeting to different parts of mitochondria: the outer membrane، the intermembrane space، the inner membrane، and the matrix. Mitochondrial proteins are sorted in five different pathway by protein complexes including protein translocases in the outer and the inner mitochondrial membrane and processing enzymes in the intermembrane space and the matrix and with help of the membrane potential، ATP or redox reactions. In this paper we discuss method of recognition، transport and insertion of proteins across and into the two mitochondrial membranes.

Development of new therapeutic agents and exploring their mode of actions for the treatment and prevention of diseases has played a critical role in the practice of medicine for many years. Unfortunately، conventional approaches have yielded very few successes in the field of drug discovery. So، there is an urgent need to change the current drug discovery process that has high cost، low efficacy، and high adverse drug reactions. During the past few years، development of high-throughput technologies enables insight into the biological mechanism of action of drugs and the discovery of novel therapeutic applications. These methods are used in many drug discovery processes in order to reduce costs and shorten cycle times. In this review، we study current high-throughput technologies in drug discovery included chemical microarray، gene expression microarray and yeast chemical-genetic assays that have generated many successes in the evaluation of chemical–protein interactions، target identification and cell-based functional analysis and summarize the potential application of each approach.

Till now a large number of major genes related to main productive and economical traits in goat have been identified. These genes have favorable effects on physiological rate، metabolism and expressing the emergence of phenotypes in terms of economical traits. Performance of these genes on main economical traits is different. Some of these genes have synergistic effects while others have antagonistic effects on the biological nature of the organism in terms of expression and emergence of phenotype of traits. Hence، breeders should be aware of actions and effects of these genes as choosing a type of particular trait can affect other traits too. Therefore، diagnosing the major genes and also the rate of mutation in them that cause changing in the expression of the gene and phenotype of economical traits، provides the possibility to search for some genetic markers related to such important economical traits for breeders. Hence، it can be used as subsidiary tool in selection of parental herd in low ages and also in direct surveying of the position of the quantitative trait and designing an eugenics program in the future. The basic and major genes in goats have a significant role in performance، metabolism، sex determination، reproduction and resistance against diseases. Therefore، the aim of this study is reviewing the major genes which are effective in productive traits such as growth traits، reproduction، milk and wool production and resistance against diseases in goat.