Biology subjects

Burbulis, I. E.

Publications and source records attributed to Burbulis, I. E..

3 recordsLinked to original sources

bioRxiv2023

Mapping the Complex Genetic Landscape of Human Neurons

When somatic cells acquire complex karyotypes, they are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, "CNV neurons"), but previous analyses of CNV neurons have been limited by relatively small sample sizes. Here, we developed an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We applied this approach to 2,125 frontal cortical neurons from a neurotypical human brain. This approach identified 226 CNV neurons, as well as a class of CNV neurons with complex karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we found that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contained fewer, but longer, genes.

neuroscience↗

bioRxiv2020

Single cell sequencing of the small and AT-skewed genome of malaria parasites

Single cell genomics is a rapidly advancing field; however, most techniques are designed for mammalian cells. Here, we present a single cell sequencing pipeline for the intracellular parasite, Plasmodium falciparum, which harbors a relatively small genome with an extremely skewed base content. Through optimization of a quasi-linear genome amplification method, we achieve better targeting of the parasite genome over contaminants and generate coverage levels that allow detection of relatively small copy number variations on a single cell level. These improvements are important for expanding accessibility of single cell approaches to new organisms and for improving the study of adaptive mechanisms.

genomics↗

bioRxiv2018

CNV Neurons Are Rare in Aged Human Neocortex

Megabase-scale somatic copy number variants (CNVs) alter allelic diversity in a subset of human neocortical neurons. Reported frequencies of CNV neurons range from [~]5% of neurons in some individuals to greater than 30% in other individuals. Genome-wide and familial studies implicitly assume a constant brain genome when assessing the genetic risk architecture of neurological disease, thus it is critical to determine whether divergent reports of CNV neuron frequency reflect normal individual variation or technical differences between approaches. We generated a new dataset of over 800 human neurons from 5 neurotypical individuals and developed a computational approach that measures single cell library quality based on Bayesian Information Criterion and identifies integer-like variant segments from population-level statistics. A brain CNV atlas was assembled using our new dataset and published data from 10 additional neurotypical individuals. This atlas reveals that the frequency of neocortical CNV neurons varies widely among individuals, but that this variability is not readily accounted for by tissue quality or CNV detection approach. Rather, the age of the individual is anti-correlated with CNV neuron frequency. Fewer CNV neurons are observed in aged individuals than young individuals.

neuroscience↗