Preimplantation genetic testing for embryos predisposed to hereditary cancer: Possibilities and challenges.

Preimplantation genetic testing (PGT), which was developed as an alternative to prenatal genetic testing, allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus. Originally used for early onset monogenic conditions, PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology, assisted reproductive techniques (ARTs), and in vitro fertilization (IVF). This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test, with a particular focus on the current challenges related to laws, ethics, counseling, and technology. Additionally, this review predicts the future potential applications of this method. Although PGT may be utilized to predict and prevent hereditary cancer, each case should be comprehensively evaluated. The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes, and non-pathogenic phenotypes must be carefully evaluated. Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning. PGT may be the preferred treatment for hereditary cancer cases; however, such cases require careful case-by-case evaluations. Therefore, this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.

The impact of chimerism on DNA-based human identification from skin surface cells of post-allogenic hematopoietic stem cell transplantation (HCST) patients.

The use of biological traces recovered from touched or handled items increased with the advance of the forensic analysis system. Thus, DNA profiles obtained from touch DNA became a useful tool in forensic investigation. However, a chimeric person with more than one chromosomal population can be challenging for a forensic analyst. We investigated the genetic profile in blood, buccal swab, and skin swabs from twenty-four recipients aged 21-63 years who underwent a matched sibling allogeneic hematopoietic stem cell transplantation with no sign of skin graft versus host disease. Autosomal short tandem repeats genotyping was performed to evaluate chimerism status at 15 loci along with gender marker Amelogenin. According to our results, donor chimerism was detected in all recipient's blood samples, while in buccal swabs, five recipients showed no presence of donor-derived cells in their genotype. Epithelial cells swabbed from hand fingertips were not devoid of donor-derived cells since all recipients showed high chimerism (39.69%-96.66%) in their genotypes. A significant change in chimerism was seen among various types of biological samples (p<0.05). No correlations were observed between chimerism and recipient age, gender, or time after transplant (p> 0.05). The loci D21S11, D8S1179, and FGA were the most informative, whereas D13S317, Vwa, and TOPX were the least informative STR markers. We concluded that touch DNA from a person who has undergone a successful allogeneic HSCTs should not be considered as reliable evidence for human identifications. Therefore, necessary precautions must be taken to avoid false identification and miscarriage of justice.

Identification of Potential Genes for Benign Prostatic Hyperplasia and Prostate Cancer Susceptibility in Four X-chromosome Regions with High Frequency of Microvariant Alleles.

BACKGROUND: The X-chromosome has been suggested to play a role in prostate cancer (PrCa) since epidemiological studies have provided evidence for an X-linked mode of inheritance for PrCa based on the higher relative risk among men who report an affected brother(s) as compared to those reporting an affected father. The aim of this study was to examine the potential association between the forensic STR markers located at four regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28 and the risk of BPH and PrCa to confirm the impact of ChrX in the PrCa incidence. This may be helpful in the incorporation of STRs genetic variation in the early detection of men population at risk of developing PrCa. METHODS: DNA samples from 92 patients and 156 healthy controls collected from two medical centers in Riyadh, Saudi Arabia were analyzed for four regions located at X-chromosome using the Investigator® Argus X-12 QS Kit. RESULTS: The results demonstrated that microvariant alleles of (DXS7132, DXS10146, HPRTB, DXS10134, and DXS10135) are overrepresented in the BPH group (p < 0.00001). Allele 28 of DXS10135 and allele 15 of DXS7423 could have a protective effect, OR 0.229 (95%CI, 0.066-0.79); and OR 0.439 (95%CI, 0.208-0.925). On the other hand, patients carrying allele 23 of DXS10079 and allele 26 of DXS10148 presented an increased risk to PrCa OR 4.714 (95%CI, 3.604-6.166). CONCLUSION: The results are in concordance with the involvement of the X chromosome in PrCa and BPH development. STR allele studies may add further information from the definition of a genetic profile of PrCa resistance or susceptibility. As TBL1, AR, LDOC1, and RPL10 genes are located at regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28, respectively, these genes could play an essential role in PrCa or BPH.

A review of studies examining the association between genetic biomarkers (short tandem repeats and single-nucleotide polymorphisms) and risk of prostate cancer: the need for valid predictive biomarkers.

Prostate cancer (PCa) is a challenging polygenic disease because the genes that cause PCa remain largely elusive and are affected by several causal factors. Consequently, research continuously strives to identify a genetic marker which could be used as an indicator to predict the most vulnerable (i.e., predisposed) segments of the population to the disease or for the gene which may be directly responsible for PCa. To enhance the genetic etiology of PCa, this research sought to discover the key studies conducted in this field using data from the main journal publication search engines, as it was hoped that this could shed light on the main research findings from these studies, which in turn could assist in determining these genes or markers. From the research highlighted, the studies primarily used two kinds of markers: short tandem repeats or single-nucleotide polymorphisms. These markers were found to be quite prevalent in all the chromosomes within the research carried out. It also became apparent that the studies differed in both quantity and quality, as well as being conducted in a variety of societies. Links were also determined between the degree and strength of the relationship between these markers and the occurrence of the disease. From the studies identified, most recommended a larger and more diverse survey for the parameters which had not been studied before, as well as an increase in the size of the community (i.e., the population) being studied. This is an indication that work in this field is far from complete, and thus, current research remains committed toward finding genetic markers that can be used clinically for the diagnosis and screening of patients with PCa.

Induction of Chronic Subclinical Systemic Inflammation in Sprague-Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide.

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-ß. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.

Evaluation of Skin Surface as an Alternative Source of Reference DNA Samples: A Pilot Study.

An acceptable area for collecting DNA reference sample is a part of the forensic DNA analysis development. The aim of this study was to evaluate skin surface cells (SSC) as an alternate source of reference DNA sample. From each volunteer (n = 10), six samples from skin surface areas (forearm and fingertips) and two traditional samples (blood and buccal cells) were collected. Genomic DNA was extracted and quantified then genotyped using standard techniques. The highest DNA concentration of SSC samples was collected using the tape/forearm method of collection (2.1 ng/µL). Cotton swabs moistened with ethanol yielded higher quantities of DNA than swabs moistened with salicylic acid, and it gave the highest percentage of full STR profiles (97%). This study supports the use of SSC as a noninvasive sampling technique and as a extremely useful source of DNA reference samples among certain cultures where the use of buccal swabs can be considered socially unacceptable.