Biology subjects

Dorgham, A.

Publications and source records attributed to Dorgham, A..

2 recordsLinked to original sources

bioRxiv2022

Characterization of the immunoglobulin lambda chain locus from diverse populations reveals extensive genetic variation

Immunoglobulins (IGs), crucial components of the adaptive immune system, are encoded by three genomic loci. However, the complexity of the IG loci severely limits the effective use of short read sequencing, limiting our knowledge of population diversity in these loci. We leveraged existing long read whole-genome sequencing (WGS) data, fosmid technology, and IG targeted single-molecule, real-time (SMRT) long-read sequencing (IG-Cap) to create haplotype-resolved assemblies of the IG Lambda (IGL) locus from 6 ethnically diverse individuals. In addition, we generated 10 diploid assemblies of IGL from a diverse cohort of individuals utilizing IG-cap. From these 16 individuals, we identified significant allelic diversity, including 37 novel IGLV alleles. In addition, we observed highly elevated single nucleotide variation (SNV) in IGLV genes relative to IGL intergenic and genomic background SNV density. By comparing SNV calls between our high quality assemblies and existing short read datasets from the same individuals, we show a high propensity for false-positives in the short read datasets. Finally, for the first time, we nucleotide-resolved common 5-10 Kb duplications in the IGLC region that contain functional IGLJ and IGLC genes. Together these data represent a significant advancement in our understanding of genetic variation and population diversity in the IGL locus.

genetics↗

bioRxiv2018

Dissociating cognitive and motoric precursors of human self-initiated action

Across-trial variability of EEG decreases more markedly prior to self-initiated than prior to externally-triggered actions, providing a novel neural precursor for volitional action. However, it remains unclear whether this neural convergence is an early, deliberative stage, or a late, execution-related stage in the chain of cognitive processes that transform intentions to actions. We report two experiments addressing these questions. Self-initiated actions were operationalized as endogenous skip responses while waiting for target stimuli in a perceptual decision task. These self-initiated skips were compared to blocks where participants were instructed to skip. EEG variability decreased more markedly prior to self-initiated compared to externally-triggered skip actions, replicating previous findings.\n\nImportantly, this EEG convergence was stronger at fronto-midline electrodes than at either the electrode contralateral or ipsilateral to the hand assigned to the skip action in each block (Experiment 1). Further, convergence was stronger when availability of skip responses was rationed, encouraging deliberate planning before skipping (Experiment 2). This suggests that the initiation of voluntary actions involves a bilaterally-distributed, effector-independent process related to deliberation. A consistent process of volition is detectable during early, deliberative planning, and not only during late, execution-related time windows.

neuroscience↗