The Genetic Basis of Defensive Structure Variation in Threespine Stickleback (Gasterosteus aculeatus)

72 pagesA longstanding goal in evolutionary biology is to link differences in traits among organisms with genetic variants in their genomes. Hybrid populations are excellent models for studies that aim to associate such phenotypic variation with regions of the genome. The Riverbend section of the McKenzie river in Oregon is home to a hybrid population of freshwater-like and ocean-like threespine stickleback (Gasterosteus aculeatus). Stickleback are small fish that live in a variety of aquatic habitats and appear highly armored in oceanic and brackish environments and often exhibit a loss of armor in freshwater systems. Previous work in this population demonstrated that variation in a handful of bony traits encompassed the differences observed between oceanic and freshwater types. I hypothesized I would see similar variation in the pelvic defensive structure–a group of bones that surround the fish and protects it from predation–and that by association mapping, I would identify genetic variants contributing to the diversity in this trait. For this thesis, I measured 12 aspects of the defensive structure in 192 fish and used 19,540 genetic markers to perform a genome-wide association analysis. Here, I show that the defensive structure and its components display abundant variation between individuals in this population. I describe the genetic architecture of this set of traits and report genetic regions of association, some of which overlap with previously discovered regions. In addition, I found novel regions of association for a subset of the traits and report candidate genes in these regions that may contribute to the phenotypic differences observed

Additive Manufacture Breakout Board

This project supports the paper by Cameron K. Brooks, Jack Peplinski and Joshua M. Pearce, Overcoming Chip Shortages: Low-Cost Open-Source Parametric 3-D Printable Solderless SOIC to DIP Breakout Adapters. Inventions 2023, 8, 61. https://doi.org/10.3390/inventions8020061 (https://www.mdpi.com/2411-5134/8/2/61

Prognostic Impact of Co-occurring Mutations in FLT3-ITD Pediatric Acute Myeloid Leukemia.

We sought to define the co-occurring mutational profile of FLT3-ITD positive (ITDpos) acute myeloid leukemia (AML) in pediatric and young adult patients and to define the prognostic impact of cooperating mutations. We identified 464 patients with FLT3-ITD mutations treated on Childrens Oncology Group trials with available sequencing and outcome data. Overall survival (OS), event-free survival (EFS), and relapse risk (RR) were determined according to the presence of co-occurring risk stratifying mutations. Among the cohort, 79% of patients had co-occurring alterations across 239 different genes that were altered through mutations or fusions. Evaluation of the prognostic impact of the co-occurring mutations demonstrated that ITDpos patients experienced significantly different outcomes according to the co-occurring mutational profile. ITDpos patients harboring a co-occurring favorable risk mutation (ITDFR) of NPM1, CEBPA, t(8;21), or inv(16) experienced a 5-year EFS of 64%, which was significantly superior to patients with ITDpos and poor risk mutations (ITDPR) of WT1, UBTF or NUP98::NSD1 of 22.2% as well as those that lacked either FR or PR mutation (ITDINT) of 40.9% (p<0.001 for both). Multivariable analysis demonstrated co-occurring mutations had significant prognostic impact, while allelic ratio had no impact. Therapy intensification, specifically consolidation transplant in remission resulted in significant improvements in survival for ITDpos AML. However, ITDpos/NUP98::NSD1 patients continued to have poor outcomes with intensified therapy, including sorafenib. Co-occurring mutational profile in ITDpos AML has significant prognostic impacts is critical to determining risk stratification and therapeutic allocation for ITDpos patients