Genetics in the Third Millennium
Volume:5 Issue: 2, 2007

The spinocerebellar ataxias (SCA) comprise a heterogeneous group of severe late-onset neurodegenerative diseases promoted by the expansion of a tandem-arrayed DNA sequence that modify the primary structure of the protein. SCA is a genetic disease with multiple types, each of which could be considered a disease in its own right, and cannot be differentiated rapidly from each other on a clinical basis. As with other forms of ataxia, SCA results in unsteady and clumsy motion of the body due to a failure of the fine coordination of muscle movements, along with other symptoms. A variety of deadly diseases are attributable to a large number of accumulated mutations in mitochondria. Percentage levels of mutant mtDNA in blood have been reported in some patients with neurological disease, usually in association with much higher levels of mutant mtDNA in skeletal muscle. Mitochondrial DNA (mtDNA) defects may present with cerebellar ataxia. MtDNA rearrangements are usually sporadic and may cause ataxia. MtDNA point mutations may be responsible for the ataxia seen in some SCA mutation negative families. Point mutations such as those affecting tRNALeuUUR are particularly common in human mitochondrial diseases. Genomic DNA of 20 patients with clinical symptoms of SCAs was purified from peripheral blood and screened for deletions in mitochondrial DNA (mtDNA). Genetic analysis Segments of the genes SCA1, SCA2, MJD (SCA3), CACNA1A (SCA6), and SCA7 harboring the CAG-repeat region were amplified in five separate reactions for molecular diagnosis for each patient. Also the sequencing of tRNALeu(UUR(, tRNALys, ATPase 6, ATPase8, COII, COIII, ND1, 16srRNA of mtDNA was performed in patients with genetically affected SCA to find out if they harbor any mutation in these regions or not.

PTEN (or MMAC1/TEP1) is a tumor suppressor gene that its mutations and deletions were detected in glioma, prostate, melanoma, Endometrium and breast cancers, abundantly. Most mutations occur in exon 5 that codes main domain of PTEN protein. PTEN acts as a lipid phosphate and is regulators of PI3/AKT kinase pathway. PTEN also is a protein phosphate that phosphorelates serine and threonine residues. PTEN with protein-phosphate function plays roles in regulation of several cellular pathways including MAPK. Considering the efficacy of novel drugs (like CCI-779) and therapeutic trials (like rapamycin) demonstrated for breast cancer therapy, influence by the inactivation of PTEN, and high incidence of breast cancer in Isfahan, the potential role of this gene in mammary carcinogenesis was further investigsted. 62 breast cancers were examined for mutations in PTEN/MMAC1 by means of polymerase chain reaction, single-strand conformation polymorphism, heteroduplex and sequencing. According to the results of this research, deletions/insertions and nucleotide changes were found in 2/62 (3%) and 5/62 (8%) of samples, respectively. This rate of mutations in PTEN promises efficacy of new drugs in treatment of patients with breast cancer in Isfahan.

Mutant genes, especially sex linked mutations can lead to fetal deaths and changing the secondary sex ratio, that can assume as long term or genetic consequences of exposure to the environmental and occupational hazards. The goals of present study were to determine the fetal deaths rate and sex ratios among progenies of workers at two high risk occupations (lead mine and dye-houses). In a cross-sectional investigation, the outcomes of all pregnancies of two high risk groups (wives of lead and dye workers) were studied for fetal deaths rate and sex ratio of live births and then statistically compared with each other and with general population. Result of pregnancies of wives of all workers of Ahangran lead mine and dye workers at Hamadan, Iran, were studied. Total of pregnancies were 545 cases and total of live births were 473. The basic primary data were collected by face to face interviews and fill appropriate questionnaires. Sex ratio of live births among pregnancies of workers of lead mine and dye-houses were 91.60 and 98.95 percent respectively. Also the rates of fetal deaths (abortions plus stillbirths) among their wives’ pregnancies were 13.15 and 13.30 percent respectively. Fetal death rates among those two groups were different with the same rate of general population (p<0.05). The results of present study showed an increase in fetal death rate and decrease in sex ratios of subject groups in comparison with general population. Working in lead mine and dye-houses as results of long-term genetic consequences in such high risk places can be subject of another survey

Recurrent miscarriages, intra-uterine fetal death, and still-birth are very common problems in obstetrics and clinical genetics. Frequently, families refer to genetic counseling centers because of these problems. Affected families are eager to know the cause of the problem, how to cope with, and how to prevent the recurrence. It should be mentioned that the level of knowledge and experience of the most of the health care professionals is low in this regard, and should be up-dated. In the past decades a significant rate of information appeared in related medical journals and books, as research papers. Most of the authorities recommend a comprehensive evaluation of these families and the products of the pregnancies. Identification of the genetic and non-genetic causes of the phenomenon and their effects on choosing an appropriate reproduction modality, are very important point that researchers are insistently following. Whenever a catastrophic event, like this, was occurred, it would be the duty of obstetricians, neonatologists, geneticists, and other specialists to counterpart very efficiently on the process of evaluation, diagnosis, management, and also providing an informative genetic counseling for these families.

Channelopathies may present in infantile and childhood periods as paroxysmal disorders with different manifestations in neurologic, cardiac and neuromuscular system. These channelopathies include genes encoding voltage-gated channels specific for sodium (SCN1A, SCN2A, SCN1B, SCN9A) and potassium (KCNQ2, KCNQ3) which account for a variety of epilepsy phenotypes ranging from mild, such as Benign familial neonatal seizures (BFNS) to severe, such as Dravet syndrome (severe myoclonic epilepsy of infancy, SMEI) and the rare and unusual syndrome. Paroxysmal extreme pain disorder (PEPD).Ligand-gated channels involved include the GABAA receptor in a variety of epilepsy phenotypes and the human glycine receptor. Mutations in five genes encoding subunits of this receptor and accessory molecules underlie hyperekplexia or stiff baby syndrome. In this article we have a brief review of these channelopathies and we hope that our readers acquire new concepts of these old diseases, not only for genetic counseling but to allow the specific treatment.

According to the recent biological research spectra, tissue engineering is an issue which has become the focus of practical medicine attention for repairing skin, skeletal and cartilage damages. As it is obvious any damage to these tissues neither repairs in a spontaneously manner nor implanting is a reliable proposal idea due to the immunogenicity response. Regarding to what have been mentioned, it is essential to apply basic tools such as scaffold, active biological molecules and cells. One of the most important steps in tissue engineering is finding appropriate cells without immunogenicity and tumorogenicity which can be divided, and able to differentiate to other tissues. Among all kind of stem cells, mesenchymal stem cells, seems to have all of these features. In this review we will introduce with the basis of tissue engineering and its profits.

Protein interactions are essential to all cellular processes, such as replication, transcription, splicing, translation and metabolism. The yeast two-hybrid system utilizes the reconstitution of an active transcription factor for assay for protein–protein interactions. The active transcription factors are formed as a dimmer between two fusion proteins, one of which contains a DNA–binding domain (DB) fused to the first protein of interest (DB-X Bait) and the other, an activation domain (AD) fused to the second protein of interest (AD–Y Prey or Target protein). DB–X:AD–Y interaction reconstitutes a functional factor that activates chromosomally integrated reporter genes driven by promoters containing the relevant DB binding sites. When a selectable marker gene such as HIS3 is used as a reporter gene, two–hybrid dependent transcription activation can be monitored by growth of yeast cells on plates lacking histidine, thereby providing a tool for detection of protein–protein interactions. Nowadays, yeast two-hybrid system is considered as a suitable approach for mapping of protein interactions in cells. This map may consist of many possible protein interactions that occur during the entire lifespan of a cell. In this review, we are going to describe this system, its efficiencies and its approaches for protein-protein interactions.

Normal function of immune system is essential for being healthy. Inappropriate function can result to many diseases and minimal hyperactivity causes allergic and autoimmune disease. Immune system is under influence of biologic, chemical and environmental factors. Cold, heat and exercise in cold are among important environmental conditions. Heat stresses have effects on production of many cytokines and induce alteration in gene expression and protein in cells. In such situations heat shock proteins have a grate role on modifying the stresses. Cold and exercise in cold have similar effect, and cold shock proteins such as CIRP and RBM3 that are the most important ones, also have effect on cell cycles in low temperatures. These responses are different according to the temperature point and duration of the stimulus. In this review, we will acquaint with these mechanisms.