Until a few years ago, it was believed that the gradual mosaic loss of the Y chromosome (mLOY) was a normal age-related process. However, it is now known that mLOY is associated with a wide variety of pathologies in men, such as cardiovascular diseases, neurodegenerative disorders, and many types of cancer. Nevertheless, the mechanisms that generate mLOY in men have not been studied so far. This task is of great importance because it will allow focusing on possible methods of prophylaxis or therapy for diseases associated with mLOY. On the other hand, it would allow better understanding of mLOY as a possible marker for inferring the age of male samples in cases of human identification. Due to the above, in this work, a comprehensive review of the literature was conducted, presenting the most relevant information on the possible molecular mechanisms by which mLOY is generated, as well as its implications for men’s health and its possible use as a marker to infer age.

Forensic genetics has experienced remarkable advancements over the past decades, evolving from the analysis of a limited number of DNA segments to comprehensive genome-wide investigations. This progression has significantly improved the ability to establish genetic profiles under diverse conditions and scenarios. Beyond individual identification, forensic genetics now enables the inference of physical traits (e.g., eye, hair, and skin color, as well as body composition), biogeographic ancestry, lifestyle habits such as alcohol and tobacco use, and even the transfer of genital microbiomes post-coitus, among other characteristics. Emerging trends point to a future shaped by the integration of cutting-edge technologies, including CRISPR-Cas systems, artificial intelligence, and machine learning, which promise to further revolutionize the field. This review provides a thorough exploration of forensic genetics, tracing its evolution from its foundational methods (past) to its diverse modern applications (present) and offering insights into its potential future directions.

Breast cancer (BC) is the leading cause of death from tumors in women worldwide, influenced by various factors, including genetics. The T allele of the single nucleotide variant (SNV) rs3025039 at position +936 of the VEGFA gene has been reported to affect the mRNA regulatory mechanisms, potentially altering VEGFA expression and increasing BC risk. This study aimed to investigate the association between rs3025039 and BC in Mexican women residing in Jalisco, Mexico. The study included 231 women with a confirmed diagnosis of BC and 201 healthy subjects as a reference group (RG). PCR–RFLP was employed for the genotyping of rs3025039, with the visualization of amplified products using polyacrylamide gel electrophoresis. Significant differences were observed in rs3025039 alleles and genotypes between BC cases and the RG (p = 0.0038). The frequency of the T allele and the CT genotype was higher in the BC group compared to the RG, with a significant difference (p = 0.0006). In conclusion, this research suggests that the SNV rs3025039 is associated with a higher risk of BC in Mexican women. These findings enhance our understanding of the genetic underpinnings of BC in this population, offering potential insights for future studies and interventions.

The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family.

Immunotherapy with antibodies targeting immune checkpoints, in combination with standard therapies, is one of the areas with the most significant clinical research, particularly in aggressive tumors such as triple-negative breast cancer, where there have been relevant advances with antibodies against PD-1/PD-L1. However, it is essential to define the biological and molecular factors that influence survival and response to immunotherapy, as other immune control points, such as CTLA-4, TIM-3, LAG-3, TIGIT, and VISTA, also play a role. The immune checkpoints were studied by microarrays and immunohistochemistry in 243 samples from patients with breast cancer, according to the molecular subtype. Significant differences in PD-1, PL-1, CTLA-4, and TIGIT expression were observed between triple-negative and Her-2 tumors compared to Luminal A and Luminal B tumors. No differences in VISTA expression were observed between the different molecular subtypes. Patients with high-grade tumors showed higher PD-1, PD-L1, LAG-3, and VISTA expression than low and intermediate-grade tumors. We observed a significant difference in PD-L1/TIGIT co-expression in tumor-infiltrating cells from patients with triple-negative tumors compared to patients with Luminal A, Luminal B, and Her2+ tumors. These results are relevant in the context of clinical application.