A unifying model that explains the origins of human inverted copy number variants.

With the release of the telomere-to-telomere human genome sequence and the availability of both long-read sequencing and optical genome mapping techniques, the identification of copy number variants (CNVs) and other structural variants is providing new insights into human genetic disease. Different mechanisms have been proposed to account for the novel junctions in these complex architectures, including aberrant forms of DNA replication, non-allelic homologous recombination, and various pathways that repair DNA breaks. Here, we have focused on a set of structural variants that include an inverted segment and propose that they share a common initiating event: an inverted triplication with long, unstable palindromic junctions.

Template switching between the leading and lagging strands at replication forks generates inverted copy number variants through hairpin-capped extrachromosomal DNA.

Inherited and germ-line de novo copy number variants (CNVs) are increasingly found to be correlated with human developmental and cancerous phenotypes. Several models for template switching during replication have been proposed to explain the generation of these gross chromosomal rearrangements. We proposed a model of template switching (ODIRA-origin dependent inverted repeat amplification) in which simultaneous ligation of the leading and lagging strands at diverging replication forks could generate segmental inverted triplications through an extrachromosomal inverted circular intermediate.

Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.

Timely completion of genome replication is a prerequisite for mitosis, genome integrity, and cell survival. A challenge to this timely completion comes from the need to replicate the hundreds of untranscribed copies of rDNA that organisms maintain in addition to the copies required for ribosome biogenesis. Replication of these rDNA arrays is relegated to late S phase despite their large size, repetitive nature, and essentiality.

Hotspot of de novo telomere addition stabilizes linear amplicons in yeast grown in sulfate-limiting conditions.

Evolution is driven by the accumulation of competing mutations that influence survival. A broad form of genetic variation is the amplification or deletion of DNA (≥50 bp) referred to as copy number variation (CNV). In humans, CNV may be inconsequential, contribute to minor phenotypic differences, or cause conditions such as birth defects, neurodevelopmental disorders, and cancers.

Comparison of Trocar Site versus Trocar Site Plus Intraperitoneal Instillation of Local Anesthetic for Shoulder Pain Following Laparoscopic Abdominal Surgery.

Background: Laparoscopic surgery in recent times has noteworthy advantages over conventional surgery, yet recovery is prolonged due to debilitating shoulder tip pain (STP) and operated site pain. Various studies have compared the effect of trocar site, intraperitoneal instillation of local anesthetic (LA) for pain relief while only a few studies have tested the combination of these two techniques. Hence, this study was undertaken to compare the combination of these two techniques versus trocar site alone for STP particularly.