Biology subjects

Shrestha, V.

Publications and source records attributed to Shrestha, V..

5 recordsLinked to original sources

bioRxiv2026

From Kernel to Kitchen: Asparagine Synthetase 3 is Involved in Free Asparagine Accumulation in Maize Kernels

Acrylamide is a probable dietary carcinogen formed through high-temperature cooking processes from one of its precursors, free asparagine (Asn). To reduce acrylamide formation potential in maize-based food products, the genetic basis for the accumulation of free Asn in maize kernels must be elucidated. In this study we integrated complementary quantitative genetic approaches including quantitative trait locus (QTL) mapping of a biparental population and genome-wide association studies (GWAS) in a diverse inbred panel. We ultimately identified one major QTL for free Asn which was not reflected in the GWAS results. Subsequent sequence analysis of the QTL mapping population parents revealed a 921bp deletion in As-paragine Synthetase 3 (ASN3) in the low Asn parent. Validation is underway with rtPCR, genotyping the association panel for the deletion, and evaluation of a CRISPR-Cas9 knockout of ASN3. This work provides a foundation for breeding and genome-editing strategies to reduce acrylamide-forming potential in maize-based foods.

Plant Biology↗

bioRxiv2024

Association of the benzoxazinoid pathway with boron homeostasis in maize

Both deficiency and toxicity of the micronutrient boron lead to severe reductions in crop yield. Despite this agricultural importance, the molecular basis underlying boron homeostasis in plants is not resolved. To identify molecular players involved in boron homeostasis in maize (Zea mays), we measured boron levels in the Goodman-Buckler association panel and performed genome-wide association studies. These analyses detected the benzoxazinless (bx) gene, bx3, involved in the biosynthesis of benzoxazinoids, like DIMBOA, major defense compounds in maize. Genes involved in DIMBOA biosynthesis are all located in close proximity in the genome and the biosynthesis mutants, including bx3 are all DIMBOA deficient. We show that the bx3 mutant has enhanced boron concentration in leaves compared to the B73 control plants, which correlates with enhanced leaf tip necrosis, a phenotype associated with boron toxicity. In contrast, other DIMBOA-deficient maize mutants did not show altered boron levels nor the leaf tip necrosis phenotype, suggesting that boron is not associated with DIMBOA. Instead, our analyses suggest that the accumulation of boron is linked to the benzoxazinoid intermediates indolin-2-one (ION) and 3-hydroxy-ION. Therefore, our results connect boron homeostasis to the benzoxazinoid plant defense pathway through bx3 and specific intermediates, rendering the benzoxazinoid biosynthesis pathway a potential target for crop improvement in inadequate boron conditions. One sentence summaryGWAS identified benzoxazinless3 in the benzoxazinoid biosynthesis pathway to play a role in boron homeostasis in maize.

plant biology↗

bioRxiv2022

Genomic mapping of the modifiers of Teosinte crossing barrier 1 (Tcb1)

Pollen cross-contamination has been a major problem for maize breeders. Mechanical methods applied to avoid cross-contamination are largely ineffective and time-consuming. Cross incompatibility barriers are genetic factors involved in maize fertilization that can be used as an effective method to prevent pollen cross-contamination. Teosinte crossing barrier 1 (Tcb1) is a cross-incompatibility system in which silks possessing dominant Tcb1-s reject pollen possessing the recessive allele (tcb1). However, successful fertilization occurs when Tcb1-s pollen falls upon tcb1 silks or under self-fertilization of Tcb1-s pollen on Tcb1-s silks. Previous studies have shown that the efficacy of dominant Tcb1-s was reduced when repeatedly backcrossing with maize inbred lines suggesting the presence of modifiers to Tcb1-s. To find those modifiers, we conducted a QTL mapping experiment using the Intermated B73 x Mo17 (IBM) recombinant inbred lines (RILs) for two consecutive years. Two significant and stable QTL were identified on chromosomes 4L and 5S explained 16% and 17.6% of the total phenotypic variation (R2), and both had negative additive effects. Further investigation of these QTL regions identified twelve candidate genes that could modify Tcb1-s activity. The introgression of the Tcb1-s genetic system, and its appropriate modifying factors, could be a novel and reliable solution for cultivar isolation in maize breeding.

plant biology↗

bioRxiv2020

HAPPI GWAS: Holistic Analysis with Pre and Post Integration GWAS

MotivationAdvanced publicly available sequencing data from large populations have enabled in-formative genome-wide association studies (GWAS) that associate SNPs with phenotypic traits of interest. Many publicly available tools able to perform GWAS have been developed in response to increased demand. However, these tools lack a comprehensive pipeline that includes both pre-GWAS analysis such as outlier removal, data transformation, and calculation of Best Linear Unbiased Predictions (BLUPs) or Best Linear Unbiased Estimates (BLUEs). In addition, post-GWAS analysis such as haploblock analysis and candidate gene identification are lacking. ResultsHere, we present HAPPI GWAS, an open-source GWAS tool able to perform pre-GWAS, GWAS, and post-GWAS analysis in an automated pipeline using the command-line interface. AvailabilityHAPPI GWAS is written in R for any Unix-like operating systems and is available on GitHub (https://github.com/Angelovici-Lab/HAPPI.GWAS.git). Contactangelovicir@missouri.edu

bioinformatics↗

bioRxiv2019

The thalamic basis of outcome and cognitive impairment in traumatic brain injury

ObjectiveTo understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at six months post-injury.\n\nMethodsLongitudinal analysis of clinical and MRI data collected, in a tertiary neurointensive care setting, in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient we collected T1- and T2-weighted MRI data, acutely and at a six-months follow-up, as well as acute measures of injury severity (Glasgow Coma Scale) and follow-up measures of functional impairment (Glasgow Outcome Scale extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.\n\nResultsIn the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first six months post-injury across the brain. Nonetheless, only atrophy within subcortical regions, particularly in left thalamus, were associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good versus bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could only achieve 20% accuracy.\n\nInterpretationDespite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute \"event\" and the long(er)-term \"disease\" of TBI.

neuroscience↗