Genetics in the Third Millennium
Volume:7 Issue: 4, 2010

Two hundred and eight asymptomatic individuals from different origins of Iran were included in this study in order to assess the distribution of the Factor V Leiden polymorphism responding for cardiovascular disease (CVD) in the general Iranian population using a novel technique reverse hybridization StripAssay for the rapid and simultaneous detection. The test is based on multiplex PCR and hybridization to a teststrip presenting a parallel array of allele-specific oligonucleotide probes. The prevalences of mutant Factor V Leiden (1.2%) in our cohort was below previously published figures on the population of Tehran (2.7%). Here we describe the distribution of mutant allele FV Leiden in different ethnicities of Iranian population and compare the results to previously reported data. Our data represent the most comprehensive study to date with respect to thrombophilic gene polymorphism in Iran.

Chromosomal aberrations are one of the causes of infertility. The major chromosomal abnormalities are usually associated with somatic abnormalities. There are also some balanced chromosomal aberrations, without somatic abnormalities however producing unbalanced gametes which result in infertility. The most common of these are balanced translocation. Among 47350 karyotypes performed in our center. There are 664 (1.4%) chromosomal translocation 47 (7%), which are associated with infertility. The sex, and chromosomal aberrations of these cases presented in this paper.

Peroxisomes are ubiquitous organelles in nearly all eukaryotes that participate in the metabolism of fatty acids and other metabolites. In order to investigate peroxisome biogenesis and gene profile expression analysis during neurogenesis, we have performed to set a semi-quantitative analysis for two peroxisomal genes expression (Catalase and PEX3) during neurogenesis comparing with stem cell marker genes (Oct4 and Nanog) in P19 cells. In this project we have used P19 cells which are suitable progenitor cells for the study of neurogenesis. Moreover, two different peroxisomal genes were selected to chase both kinetics of peroxisomal matrix protein synthesis (Catalase) and peroxisomal membrane protein biogenesis (Pex3p). Total RNA extracted from P19 cells, and was used for cDNA synthesis at the next step. Specific primers of Oct4, Nanog, PEX3 and Catalase cDNAs were amplified by RT-PCR for quantitative analysis. Various parameters were changed to optimize the PCR profiles for each gene for further assessments. Here we are going to describe the conditions which we used, e.g.: PEX3 band was detected sharply after 35 cycles and at annealing temperature of 52.5-55.1°C. For PCR of Catalase we observed a sharp band after 35 cycles and annealing temperature of 52.7-55°C. Nanog cDNA was amplified after 36 cycles and between 60.1-64.1°C. Oct4 band was observed sharply after 28 cycles of amplification and annealing temperature in range of 53.4-57°C.

Mesenchymal Stem Cells are pluripotent cells differentiating through development from mesenchymal cells.This cells have the potential to differentiate to osteoblasts, osteocytes, adipocytes and cartilage cells. In vitro differentiation to osteoblasts needs various factors to produce a microenvironment mimicking the natural microenvironment in bone tissue. In this research the effect of Dexamethazone, ascorbic acide and beta glycerolphosphate on the differentiation process of bone marrow mesenchymal stem cells to osteocytes is investigated. Mesenchymal stem cells were separated from 2 ml aspirated bone marrow using ficole, HBSS, and the attachment ability of mesenchymal stem cells to plastic surfaces. Different markers and Alizarin red staining were implemented to study the success of in vitro differentiation Mesenchymal stem cells were fusiform in the beginning and after differentiation the phenotype changed to calcium producing cells. Staining with Alizarin red confirmed this process. RT-PCR on osteocalcin and alkalin phosphatase showed a change from negative expression to positive expression. These results show that in vitro osteoblastogenesis from mesenchymal stem cells is confirmed and these cells could be implemented as a model to study genetic and epigenetic factors in the differentiation cells.

Congenital adrenal hyperplasia (CAH) is a group of the disorders resulted from enzymatic defects in the corticosteroid synthesis. The most prevalent type is 25 hydroxylase deficiency that is due to the defect in the gene CYP21A2. The aim of this study was to determine correlation between phenotype and genotype of Iranian patients with this disorder. We reviewed the medical records of 89 patients with CAH who were investigated for their genetic aspects before. Salt wasting (SW) form was seen in 70 patients (79%), salt wasting with balanced electrolytes in 4 (4.5%), simple virilizing (SV) in 12 (13.5%) and non classical in 1 (1.1%). Interon2-interon2 (int2-int2) mutation was the most prevalent type of mutation (35%). In this group 31 from 27 patients (87%) had SW form of CAH. From 12 cases of simple virilizing type, 9 patients (75%) had Ex4 mutation. In the int2-int2 group, 7 from 15 patients (47%) had grade 4 and 4 (27%) had grade 5 of Prader staging. Fifty seven from 82 patients (69.5%) were the product of consanguineous marriages. int2-int2 mutation is the most prevalent type of mutation in this study. In this group salt wasting type and severe virilization is more common. Simple virilizing type was most often accompanied by Ex4 mutation.

Microdeletions are a group of chromosomal disorders caused by the deletion of a segment of DNA smaller than 5 megabases. They are inherited as an autosomal dominant trait. Despite the relatively small segment of chromosomal loss affected individuals present with severe and diverse clinical manifestations. The deletion is often beyond the resolution of cytogenetic study and will be missed by routine karyotyping. In cases where any of the microdeletion syndromes are being considered it is necessary to apply more sensitive techniques. Towards this purpose and for the standardization of FISH technique in detection, we proposed to do a prospective study on patients referred for microdeletion syndrome by FISH. In complete clinical, laboratory, radiographical and cytogenetic study of 68 families for microdeletion syndromes, 12 cases were referred with suspicion of having di George syndrome (DGS). Two amniotic fluid samples were received from a multiparous female with a former child with DGS and the other of a fetus with thymus hypoplasia and aortic arch deviation detected in sonography. Cytogenetic study by GTG banding and FISH showed the presence of the critical region on chromosomes 22 for both cases ruling out DGS. From the ten blood samples, one failed to grow. Of the nine remaining samples, in the cases of a two year old girl, both cytogenetic study and FISH detected a deletion of 22q11.2 region confirming the diagnosis of DGS. In the other eight cases, the presence of the critical region on both chromosomes was confirmed by FISH and the diagnosis of DGS was not confirmed. In view of the fact that of 11 cases referred for DGS, only one cases was confirmed to be DGS, and considering that DGS is phenotypically and genotypically heterogeneous, it appears that further clinical workup will lead to better diagnosis.

With 1 million new cases causing 375000 deaths worldwide per year, breast cancer is the leading cause of cancer death in women in both developing and developed countries. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. Epigenetic refers to the cellular information of transcription memory which is transmitted through cell divisions but is not sequence based. Epigenetic is the connecting circle of the genotype and the environment. Which connect the inheritable gene transcription pattern and phenotype of a cell. DNA promoter methylation and chromatin remodeling are two main mechanisms of epigenetic modifications which are emerging as targets for breast cancer detection, prognosis and treatment. Because of their potential for reversal, epigenetic alterations are considered to be promising in caner treatment and epidrug production. Therapeutics that target methylation and histone modifications in breast cancer already exist. Advances in epidrugs are likely to play important role in future of cancer treatment.

Learning disorders are of frequent neurobehavioral disorders within the primary school children. Is frequency differs between 5 to 12%. The persons who are suffering are unable to get reading and writing skills. Several genetic loci have been related for this disorder so far. The most important genes are DCDC2, KIAA0319, DYX1C1 and ROBO1. The products of these genes are responsible for different processes for brain development like neural immigration. Thus dysfunctions of these genes are responsible for the incidence of this disorder. We will introduce with genetic basis of this disease in this article.

Adeno-associated virus (AAV) is a small virus encapsidates a single-stranded DNA genome. AAV have rapidly gained popularity as a vector in genetic engineering and gene therapy applications, due to its lack of pathogencity, wide range of infectivity, and ability to integrate into human genome (19q13.4). Recombinant AAV vectors have been used for treatment of a variety of diseases such as hemophilia, cystic fibrosis, and Parkinson. A challenge with wide application of this vector is the relatively small packaging size of the viral genome to enable the delivery of a large transgene. Therefore it is essential making changes in it to overcome this problem. In this review we will introduce with this virus and the new finding in reginal of gene therapy with this virus.

A 29 years old girl with various dimorphic features including short stature and webbed neck with mild to moderate mental retardation was referred to our center for chromosome investigation. Her parents were first cousins. The mother has had two previous miscarriages, one deceased son (12 years old) with apparently similar abnormal features to the proband with congenital heart problems, and one normal son (27 years old). The patient, her mother and the brother, all were found to have an apparently balanced reciprocal translocation between the long arms of chromosomes 4 and 10. The breakpoint on chromosome 4 is at the distal end (4q35), while for chromosome 10, it is proximal to the centromere (10q11.2). FISH studies using multiprobe subtelomeric specific probes as well as whole chromosome paints for chromosomes 4 and 10 were carried out in search of a genetic imbalance. The FISH results revealed no telomeric rearrangements and confirmed the balanced reciprocal translocation between chromosomes 4 and 10. To date, this is the first reported case of t(410)(q35q11.2).

Cockayne Syndrome is a rare autosomal recessive disorder characterized by profound postnatal growth deficiency with loss of adipose tissue, microcephaly, mental retardation, unsteady gait and peripheral neuropathy. We are reporting a 6-year-old girl with severe growth and developmental delay, microcephaly, mental retardation, sunken eyes and photosensitive dermatitis. Her diagnosis confirmed by a defect in DNA repair in fibroblast followed exposure to ultraviolet light.