Biology subjects

Marco, E.

Publications and source records attributed to Marco, E..

4 recordsLinked to original sources

bioRxiv2026

Whole-genome sequencing of a mid-20th-century femur from central Israel in an open missing-person case

Genome-wide technologies can generate investigative leads in cold cases by determining the genetic ancestry of the forensic sample. Increasingly, DNA extraction and whole-genome sequencing or genotyping are being used to analyze early or middle-20th century skeletal remains. Here, we present the first case, to our knowledge, of whole-genome sequencing of a middle-20th-century bone sample from the Middle East. A femur discovered in a cave in Central Israel was proposed to belong to a person of Ashkenazi Jewish ancestry who was missing since 1948. Following DNA extraction and single-stranded library preparation, whole-genome sequencing generated nearly 500 million reads. However, only 0.5% of the reads mapped to the human genome, providing depth of coverage of 0.07x. After quality control and male sex inference, ancestry assignment was performed using principal components and ADMIXTURE analyses. The results suggested that the genome definitively belonged to a person of Arab ancestry, refuting the hypothesis of an Ashkenazi Jewish origin.

genetics↗

bioRxiv2024

Global MEG Resting State Functional Connectivity in Children with Autism and Sensory Processing Dysfunction

Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.

neuroscience↗

bioRxiv2021

Pathogenic MAST3 variants in the STK domain are associated with epilepsy

ObjectiveThe MAST family of microtubule-associated serine-threonine kinases (STK) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum. MethodsUsing exome sequencing we identify MAST3 missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells. ResultsWe identify de novo missense variants in the STK domain in 11 individuals, including two recurrent variants p.G510S (n=5) and p.G515S (n=3). All 11 individuals had Developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at < 2 years of age. All patients developed multiple seizures types, while 9/11 had seizures triggered by fever and 9/11 had drug-resistant seizures. In vitro analysis of HEK293T cells transfected with MAST3 cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wildtype. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows that MAST3 expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally. InterpretationIn summary, we describe MAST3 as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex.

genetics↗

bioRxiv2017

The experimental design and data interpretation in “Unexpected mutations after CRISPR–Cas9 editing in vivo” by Schaefer et al. are insufficient to support the conclusions drawn by the authors

To the Editor To the Editor Conflict of Interest Statement References References The recent correspondence to the Editor of Nature Methods by Schaefer et al.1 has garnered significant attention since its publication as a result of its strong conclusions contradicting numerous publications in the field using similar analytical approaches and methods2-4. The authors suggest that the CRISPR-Cas9 system is highly mutagenic in genomic regions not expected to be targeted by the gRNA. We believe that the conclusions drawn from this study are unsubstantiated by the disclosed experiments as they were designed and carried out. Further, it is impossible to ascribe the observed differences in the subject mice to the effects of CRISPR per se. The genetic differences seen in ...

genetics↗