Genetics in the Third Millennium
Volume:11 Issue: 3, 2013

Congenital heart defects constitute a high percentage of congenital malformations. After presenting a hypothesis concerning the multifactorial etiology of these disorders، the importance of genetic susceptibility in congenital heart defects has been highlighted. In this regard، various genetic tests are under investigation in research laboratories and clinics. This article introduces some of the most common diagnostic genetic tests that are currently used in clinical diagnosis of congenital heart defects. These techniques are divided into two categories، modern molecular techniques such as Q-PCR and MLPA، and cytomolecular techniques such as FISH and Array-CGH that are used to identify loci and genes associated with congenital heart defects. Considering the role of the new technique of NGS in determining the genetic causes of diseases، the diagnosis and treatment of many diseases with unexplained genetic causes would tremendously change. In this manuscript، we discussed new diagnostic tests that can be used used in detecting the genetic causes of several common congenital heart defects or chromosomal microdeletion syndromes such as Di George، William - Bern، Noonan، etc. This article provides good information on the proper use of genetic tests for the medical community، especially cardiologists، obstetricians، and gynecologists and might help them to make appropriate decisions in prevention and treatment approaches.

Human papillomaviruses (HPVs) are small non-enveloped viruses with a a double-stranded DNA. The genome of HPVs encodes a number of early and late proteins. These viruses can be classified into high risk and low risk groups according to production of malignant lesions. In the present study، we analyzed the synonymous codon usage in coding sequences of high and low risk human papillomavirus genomes. The synonymous codon usage of these two groups was obtained from http: //www. kazusa. or. jp/codon and analyzed using the ROC software. Statistical data analysis indicated that the usage of five codons of UAU (tyrosin)، UGU (cysteine)، ACA (threonine)، AGG (argenine)، and GUC (valine) was significantly different between high and low types. The results of our study revealed the usefulness of codon usage analysis for the classification of high and low risk human papillomavirus.

Breast cancer is the most common malignancy in women with a prevalence of 0. 15% in Iran. Adipokines produced by the adipose tissue have been studied in relation to the risk of breast cancer. Adiponectin is an adipocyte-secreted hormone. The inverse correlation between serum adiponectin levels and the risk of postmenopausal breast cancer has been recently documented. Genetic polymorphisms in the promoter region of the adiponectin gene are associated with the differences in adiponectin serum levels. The purpose of this study was to explore the relationship between -11377 G/C adiponectin gene polymorphism and the risk of postmenopausal breast cancer in Iranian patients. Blood samples of 100 females with postmenopausal breast cancer (age rang: 54. 8±10. 1) and 100 age- and sex-matched healthy individuals (age rang: 55. 3±6. 7) were collected. The genotypes were determined using a polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) method. In the dominant effect of the G allele (comparison between GG + GC vs. CC)، the GG+GC genotypes were associated with the risk of postmenopausal breast cancer (OR= 4. 6، %95CI= 1. 2-17. 6، P= 0. 03). It is concluded that the G allele may act as a dominant allele to increase the risk of postmenopausal breast cancer.

Breast cancer is a hormone-dependent tumor which is regulated by steroid hormones including estrogen and progesterone. Therefore، estrogen-related receptors (ERRs) which belong to orphan nuclear receptor groups can interfere with the estrogen signaling pathway and cause the growth of solid tumors. In the present study، blood samples of 150 women with breast cancer and 150 healthy women were collected from Omid (Seyedoshohada) Cancer Hospital، Isfahan University of Medical Sciences and Clinical Laboratory، Alzahra Hospital، Isfahan University of Medical Sciences، Iran، respectively. DNA was extracted and amplified. Then، some of the alleles in variable sizes were sequenced and used as allele specific markers for exact determination of the number of AAAG repeats in other samples. This study was performed to determine the association between breast cancer risk and alleles of the tetranucleotide repeat (AAAG) n microsatellite in the intron of the ERRγ gene. Our results showed that women with short AAAG repeats were at higher risk of breast cancer (OR=7. 14). These results suggest the possible involvement of the polymorphic AAAG repeat of the ERRγ gene in regulating its expression. Therefore، the shortest alleles of this polymorphism with 6 and 7 repeats of AAAG may be useful as a biomarker for breast cancer prognosis.

Chromosomal aberrations are one of the major reasons of congenital diseases. The most common chromosomal abnormality is translocation، especially Robertsonian translocation. Among 88900 karyotypes that were analyzed in our center، there were 1542 cases translocation of which 387 (25%) were Robertsonian. There were also 38 (3. 3%) cases of t (11،22)، which was the most common translocation in 1165 cases of non Robertsonian translocation. The high prevalence of abortion in the carriers of balanced translocation and the adverse manifestations of non balanced t (11،22) demand attention، especially in women with recurrent miscarriage.

Available genomic data and genome-wide association virtual studies provide the possibility of genetic markers detection known to be associated with complex diseases. Genome Wide Associated Studies (GWAS)، which involve direct testing of genetic polymorphisms in large series of disease cases versus controls، provide a powerful approach to identify lower penetrance alleles that cannot be already detected by genetic linkage studies. By utilizing computer and software systems، it is possible to detect the association of SNPs with diseases without prior knowledge of the function or position. GWAS has been conducted in five of the most common cancer types: breast، prostate، colorectal، lung، and melanoma. GWAS of the breast cancer was performed by simulation of 7 known SNPs on chromosomes 2، 5، 6، 8، 10، 11 and 16 for 10000 women. A simulation study was performed using GWASimulator software and data were analyzed by R software (SNPassoc package). The strongest associations were found for rs2981582 in the FGFR2 gene. SNPs rs889312، rs2180341 and rs3817198 were associated with breast cancer. However، SNPs rs13387042، rs2180341 and rs13281615 on chromosomes 2، 6، and 8 were not associated with the disease، which requires more cases and controls to be stimulated. The results of this research showed that the detection of SNPs associated with the disease was easily possible through employing virtual systems based on real data of Hap Map project using R software.

Genomic DNA extraction with high quantity and quality is one of the basic necessities of molecular genetic studies. Therefore، nowadays، various methods for extracting DNA from different organisms and tissues are used. Non destructive and non-lethal sampling methods are preferred for conservation reasons. This study introduces an optimal method for extracting DNA from two non-lethal sample tissues of the pike through comparing three methods of phenol - chloroform، saturated NaCl، and ammonium acetate. Ninety samples of the pike fins and scales were collected from Gilan and Mazandaran. Nanodrop and electrophoresis on 1 % agarose gel were used for evaluating the quality and quantity of extracted DNA samples. Also amplification ability of the DNA was assessed with microsatellite markers using the ELU19 primer. Based on the results، the best efficiency، if the DNA concentration was important، was achieved by the phenol - chloroform method and the fin tissue. The saturated salt method from the fin or scale tissues showed higher efficiency if the DNA concentration was less important. According to the results of PCR-SSCP، amplified bands were 150bp. DNA samples of the fin tissue using phenol – chloroform and saturated salt methods showed sharper bands in comparison with the scale tissues in all three methods. So، the saturated salt method seems to be a suitable method for DNA extraction from pike tissues because it uses less toxic materials and is inexpensive.

Hemoglobinopathies are a group of genetic disorders of globin chain synthesis which are common in many countries including Iran. The hemoglobinopathies include hemoglobin D، S، C، Lepore، Setif، CS، Q، J and other hemoglobin chain disorders. By 2009، more than 900 Hemoglobin (Hb) variants were reported due to globin gene mutations that cause structural changes in globin gene products which ultimately affect the performance and stability of Hb. There is variation in the prevalence of hemoglobinopathies in different regions and ethnic groups of the country. Hemoglobin disorders are fairly common in Iran. It is estimated that 0. 5-1% of the Iranian population carries the genes for Hb abnormalities such as D، S، G and E. In this article، we reviewed 50 published papers on rare hemoglobinopathies from Iran.

Multiple sclerosis (MS) is a chronic and potentially debilitating disease that affects the central nervous system including the brain and spinal cord. The disease is an «autoimmune disease» meaning that the immune system attacks parts of the body as a foreign body. Although the primary cause of MS is unknown، its pathogenicity clearly involves inflammatory demyelinating and autoimmune-mediated axon damage. The first event in this disease is the loss of blood brain barrier that is associated with destruction of myelin and vascular infiltration of lymphocytes and monocytes into the surrounding tissue. Macrophages as the main factors and B lymphocytes associated with increased plasma cells around small blood vessels play an effective role in the destruction of CNS myelin. Also، increased production of inflammatory factors such as cytokine and activation of the complement system following the activity of the immune system in the brain are considered the effective factors in damaging axon fibers in demyelinated areas and neurodegeneration.