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Allan, A. J.

Publications and source records attributed to Allan, A. J..

2 recordsLinked to original sources

The Preclinical Animal Network (PCAN): Integrative high-throughput phenotyping of standardized mouse models for Prader-Willi syndrome

The Preclinical Animal Network (PCAN) is a collaborative resource established to advance translational research and therapeutic development for Prader-Willi syndrome (PWS), a rare neurodevelopmental disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. PCAN integrates standardized, high-throughput phenotyping of approximately 1,000 mice across six engineered lines carrying paternal deletions of Ndn, Magel2, Snord116, Ipw, and multigenic loci. Using validated experimental pipelines spanning metabolic, behavioral, and developmental domains, we captured comprehensive phenotypic profiles by applying a statistical variance-decomposition framework to partition genetic and environmental contributions. This analysis provides robust genotype-phenotype maps, revealing shared and model-specific phenotypic effects while accounting for key confounding factors. The PCAN resource provides a framework for evaluating PWS-relevant phenotypes and benchmarking therapeutic strategies. By providing open access to its mouse models, datasets and analytical resources, PCAN enables the research community to apply standardized, reproducible workflows and accelerate the development of targeted, mechanism-based treatments.

genetics↗

Application of long-read sequencing for robust identification of correct alleles in genome edited animals

Recent developments in CRISPR/Cas9 genome editing tools have facilitated the introduction of more complex alleles, often spanning genetic intervals of several kilobases, directly into the embryo. These techniques often produce mosaic founder animals and the introduction of donor templates, via homologous directed repair, can be erroneous or incomplete. Newly generated alleles must be verified at the sequence level across the targeted locus. Screening for the presence of the desired mutant allele using traditional sequencing methods can be challenging due to the size of the desired edit(s) together with founder mosaicism. In order to help disentangle the genetic complexity of these animals, we tested the application of Oxford Nanopore long read sequencing of the targeted locus. Taking advantage of sequencing the entire length of the segment in each single read, we were able to determine whether the entire intended mutant sequence was present in both mosaic founders and their offspring.

molecular biology↗