Hamid, R. | Search bioRxiv

bioRxiv2018

Choline Transporter in α/β core neurons of Drosophila mushroom body non-canonically regulates pupal eclosion and maintains neuromuscular junction integrity

Insect mushroom bodies (MB) have an ensemble of synaptic connections well-studied for their role in experience-dependent learning and several higher cognitive functions. MB requires neurotransmission for an efficient flow of information across synapses with the different flexibility to meet the demand of the dynamically changing environment of an insect. Neurotransmitter transporters coordinate appropriate changes for an efficient neurotransmission at the synapse. Till date, there is no transporter reported for any of the previously known neurotransmitters in the intrinsic neurons of MB. In this study, we report a highly enriched expression of Choline Transporter (ChT) in Drosophila MB. We demonstrate that knockdown of ChT in a sub-type of MB neurons called /{beta} core (/{beta}c) neurons leads to eclosion failure, peristaltic defect in larvae, and altered NMJ phenotype. These defects were neither observed on knockdown of proteins of the cholinergic locus in /{beta}c neurons nor by knockdown of ChT in cholinergic neurons. Thus, our study provides insights into non-canonical roles of ChT in MB.

developmental biology↗

bioRxiv2018

Programmatic Detection of Diploid-Triploid Mixoploidy via Whole Genome Sequencing

PurposeMixoploidy is a type of mosaicism where an organism is a mixture of cells with different numbers of chromosomes. There are a broad range of phenotypes associated with mixoploidy that vary greatly depending on the fraction of cells that are non-diploid, their chromosome number, their distribution, and presumably the specific variation present in the patient. Clinical detection of mixoploidy is important for diagnosis.\n\nMethodsWe developed a method to detect mixoploidy from clinical whole genome sequencing (WGS) data through the identification of excess of variant calls centered on unusual B-allele frequencies. Our method isolates the signal from these variants using trio calls and then solves a basic linear equation to estimate levels of diploid-triploid mixoploidy within the sample.\n\nResultsWe show that our method reflects the results from a cytogenetic test. We provide examples detailing how our method has been used to identify diploid-triploid mixoploid individuals from within the NIH Undiagnosed Diseases Network. We present confirmatory findings obtained by clinical cytogenetic testing and show that our method can be used to identify the diploid-triploid ratio in these cases.\n\nConclusionWGS data from patients with rare diseases can be used to identify mixoploid individuals. Individuals with certain characteristics as discussed should be tested for mixoploidy as part of standard clinical pipeline procedures. Scripts that perform this calculation are publicly available at https://github.com/HudsonAlpha/mixoviz.

genomics↗