Biology subjects

LaCombe, J.

Publications and source records attributed to LaCombe, J..

2 recordsLinked to original sources

bioRxiv2024

Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model

Skeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits and Dyrk1a was trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21. Summary StatementAnalyzing developing bone and gene expression in Ts65Dn Down syndrome model mice revealed timepoints during development when trisomic Dyrk1a overexpression linked to appendicular skeletal abnormalities. Dyrk1a was not always overexpressed.

genetics↗

bioRxiv2024

Deterministic Formulas and Procedures for Stochastic Trait Introgression Prediction

Key messageWe derive formulas for the background noise during trait introgression programs and use these formulas to quickly predict noise for up to five future generations without using simulation. Trait introgression is a common method for introducing valuable traits into breeding populations and inbred cultivars. The process involves recurrent backcrossing of a donor individual (and its descendants) with a desirable, inbred line that lacks the aforementioned traits. The process typically concludes with a final generation of selfing in order to recover lines with the traits of interest fixed in the homozygous state. The particular breeding scheme is usually designed to maximize the genetic similarity of the converted lines to the recurrent parent while minimizing a breeders cost and time to recovering the near isogenic lines. Thus, key variables include the number of generations, number of crosses, and how to apply genotyping and selection during the process. In this paper, we derive analytical formulas that characterize the stochastic nature of residual donor geneome (i.e., "background noise") during trait introgression. We use these formulas to predict the background noise in simulated trait introgression programs for five generations of progeny, as well as to construct a novel mathematical program to optimally allocate progeny to available parents. This provides a framework for the design of optimal breeding schemes for trait introgression involving one or more traits subject to the requirements of specific crops and breeding programs.

genomics↗