DNA, Volume 3, Issue 1 (March 2023) – 4 articles

Preimplantation genetic testing for structural rearrangements (PGT-SR) was one of the first applications of PGT, with initial cases being worked up in the Delhanty lab. It is the least well-known of the various forms of PGT but nonetheless provides effective treatment for many carrier couples. Structural chromosomal rearrangements (SRs) lead to infertility, repeated implantation failure, pregnancy loss, and congenitally affected children, despite the balanced parent carrier having no obvious phenotype. A high risk of generating chromosomally unbalanced gametes and embryos is the rationale for PGT-SR, aiming to select for those that are chromosomally normal, or at least balanced like the carrier parent. PGT-SR largely uses the same technology as PGT-A, i.e., initially FISH, superseded by array CGH, SNP arrays, Karyomapping, and, most recently, next-generation sequencing (NGS). Trophectoderm biopsy is now the most widely used sampling approach of all PGT variants, though there are prospects for non-invasive methods. In PGT-SR, the most significant limiting factor is the availability of normal or balanced embryo(s) for transfer. Factors directly affecting this are rearrangement type, chromosomes involved, and sex of the carrier parent. De novo aneuploidy, especially for older mothers, is a common limiting factor. PGT-SR studies provide a wealth of information, much of which can be useful to genetic counselors and the patients they treat. It is applicable in the fundamental study of basic chromosomal biology, in particular the purported existence of an interchromosomal effect (ICE). An ICE means essentially that the existence of one chromosomal defect (e.g., brought about by malsegregation of translocation chromosomes) can perpetuate the existence of others (e.g., de novo aneuploidy). Recent large cohort studies of PGT-SR patients seem, however, to have laid this notion to rest, at least for human embryonic development. Unless new evidence comes to light, this comprehensive review should serve as a requiem. Full article

Rapid and modular assembly of DNA parts is crucial to many synthetic biologists. This can be achieved through Golden Gate assembly, which often requires purchase and delivery of new primers for each part and assembly configuration. Here, we report on a small set of primers that can be used to amplify any DNA from the Registry of Standard Biological Parts for Golden Gate assembly. These primers bind to regions common to the backbone plasmid for these parts, but pair imperfectly and introduce type IIS restriction enzyme sites in a way that minimizes assembly scars. This approach makes redesign of assembly strategies faster and less expensive and can help expand access to synthetic biology to a wider group of scientists and students. Full article

Both the number of cells and the collective genome of the gut microbiota outnumber their mammalian hosts, and the metabolic and physiological interactions of the gut microbiota with the host have not yet been fully characterized. Cancer remains one of the leading causes of death, and more research into the critical events that can lead to cancer and the importance of the gut microbiota remains to be determined. The gut microbiota can release microbial molecules that simulate host endogenous processes, such as inflammatory responses, or can alter host metabolism of ingested substances. Both of these reactions can be beneficial or deleterious to the host, and some can be genotoxic, thus contributing to cancer progression. This review focused on the molecular evidence currently available on the mechanistic understanding of how the gut microbiota are involved in human carcinogenesis. We first reviewed the key events of carcinogenesis, especially how DNA damage proceeds to tumor formulation. Then, the current knowledge on host DNA damage attributed to the gut microbiota was summarized, followed by the genotoxic endogenous processes the gut microbiota can induce. Finally, we touched base on the association between specific gut microbiota dysbiosis and different types of cancer and concluded with the up-to-date knowledge as well as future research direction for advancing our understanding of the relationship between the gut microbiota and cancer development. Full article

DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in guanine-rich sequences. Within the human genome, G4s are found in regulatory regions such as gene promoters and telomeres to control replication, transcription, and telomere lengthening. In the cellular context, there are several proteins named as G4-binding proteins (G4BPs) that interact with G4s, either anchoring upon, stabilizing, and/or unwinding them. These proteins may play different key roles in the regulation of the endogenous G4 landscape and its associated functions. The present review summarizes the current literature on G4BPs in terms of their targets and functions, providing updated insights into the regulation of G4s in living organisms. Full article