فهرست مطالب زهرا فاضلی عطار

Backgrond: Infertility affects 15% of couples and male factor infertility is involved in 50% of cases. One of the causes of infertility is Azoospermia that refers to the absence of sperm per ejaculation and almost affects 1% of the total men population. A comprehensive overview about the disease and its risk factors along with a better understanding of the diagnosis was performed and comprehensive information about the modern treatment methods for this reproductive disorder was provided.
For writing this article, a large study on azoospermia, the reasons and treatment methods was performed by searching the words including azoospermia, genetics, treatment and diagnosis in the medical valid databases, mainly PubMed, up to 2016. Among the collected papers, articles that are most relevant to the goals of the present article was selected. The articles with brief explanation about the etiology of azoospermia and disease treatment options were studied further.
Findings: Literature review showed that genetic diseases such as Klinefelter syndrome, cystic fibrosis, primary and secondary testicular failure due to hormonal and/or chromosomal anomalies ranging from structural or numerical changes, gene mutations, genomics alterations at the level of telomeres and the resulting apoptosis, genetic polymorphisms, anatomical disorders associated with vas deferens and ejaculation, age, treatments of testicular cancer and other diseases, varicocele and surgical treatment of testis were considered as the most important factors in azoospermia.
Although numerous factors are involved in the etiology of azoospermia, clinical tests and genetic counseling plays an important role in early detection of disease that helps to retrieve sperm production and fertility to the patient in many cases.
Accurate understanding of the etiology of azoospermia could provide a suitable treatment approach for the management of disease.

GJB2 gene encodes connexin 26 which is an important skin-expressed gap junction protein. Connexin 26 is a transmembrane protein that is involved in the potassium ion recycling pathway in the inner ear. In this study, the neutrality tests were performed on genotyping data obtained from three polymorphic markers SNP1245, D13S141 and D13S175, located within the GJB2 region. The population genetics analysis packages, PyPop and Popgene32, were used for the analysis of the data obtained from Iranian population. Fnd value of three markers, SNP1245, D13S141 and D13S175, in Iranian population was estimated -0.5980, -1.0155 and -0.6457, respectivelybut without significant P values. The results indicated the influence of balancing selection on polymorphic markers at GJB2 gene. In the studied population, the F value of three markers lied inside L95 and U95 region of expected F value which showed no effect of genetic hitchhiking on markers located within GJB2 region. The results obtained from this study indicated that the polymorphism of these three markers in GJB2 gene was maintained by higher adaptive value of heterozygotes in Iranian population.

In this study, the genetic diversity and neutrality test for the MHC microsatellite loci, D6S2879 and D6S2806, located within the HLA-DRB1 gene region, were investigated. The genotyping data from 73 unrelated individuals were analyzed for Shannon index, the effective allele number of the markers and neutrality test by use of PyPop and Popgene32 programs. The Shannon index for D6S2879 and D6S2806 markers in the studied population was 1.0372 and 0.8601, respectively. The Fnd value computed for D6S2879 and D6S2806 markers were also estimated -0.8449 and 0.9904, respectively. The results obtained from Ewens-Watterson test indicated that D6S2879 and D6S2806 markers were under balancing and directional selection in the Iranian populations, respectively. The data suggested the presence of a selection force on HLA-DRB1 gene region in the Iranian populations.

Two polymorphic markers including BglII and EcoRI, were identified at intron 1 and intron 5 of PAH gene. In order to test whether these polymorphisms are behaving as neutral alleles or are being subjected to selective pressures in Isfahan population, 110 individuals were genotyped by PCR-RFLP. The Arlequin input file was prepared by use of phase-known haplotype data and Neutrality tests (Tajima D test and Fu’s Fs test) were done using Arlequin program. 42 individuals were found heterozygous for both polymorphisms whose haplotype phase remained unknown. The BglII-EcoRI haplotype phase was known only at 68 individuals who were used for preparation of input file. Tajima's D value and Fs value at Isfahan population were 1.7 and 1.02, respectively. Positive values of Fs and D>0 indicated that these polymorphisms are under selection pressure at Isfahan population. Although these polymorphisms were in the non-coding region of PAH gene, but these were not neutral alleles and positive values of these tests provided evidence for balancing selection of these polymorphisms at Isfahan population. The results of this study could improve our understanding of evolutionary history and structure of Isfahan population.

In this study, PvuII(a), Msp I and variable number of tandem repeat (VNTR) markers at the phenylalanine hydroxylase (PAH) gene region were genotyped in 100 unrelated individuals and 20 families from Iranian population. The allele frequency, observed heterozygosity and frequency of PvuII(a)-MspI-VNTR haplotype was estimated. Among the estimated haplotypes by use of FBAT program, eight haplotypes were introduced as informative haplotypes at the PAH gene region in the population studied, which could be used in carrier detection of phenylketonurai (PKU).