Biology subjects

Roth, C.

Publications and source records attributed to Roth, C..

3 recordsLinked to original sources

bioRxiv2018

Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates, and humans

Targeting genes to specific neuronal or glial cell types is valuable both for understanding and for repairing brain circuits. Adeno-associated viral vectors (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is a challenge. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that ~11% of these AAVs specifically target expression to neuronal and glial cell types in the mouse retina, mouse brain, non-human primate retina in vivo, and in the human retina in vitro. We demonstrate applications for recording, stimulation, and molecular characterization, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast, and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

neuroscience↗

bioRxiv2017

A High Resolution Map of Meiotic Recombination in Cryptococcus Demonstrates Decreased Recombination in Unisexual Reproduction

Multiple species within the basidiomycete genus, Cryptococcus, cause cryptococcal disease. These species are estimated to affect nearly a quarter of a million people leading to approximately 180,000 mortalities, annually. Sexual repro-duction, which can occur between haploid yeasts of the same or opposite mating type, is a potentially important contributor to pathogenesis as recombination can generate novel genotypes and transgressive phenotypes. However, our quantitative understanding of recombination in this clinically important yeast is limited. Here we describe genome-wide estimates of recombination rates in Cryptococcus deneoformans and compare recombination between progeny from - unisexual and a- bisexual crosses. We find that offspring from bisexual crosses have modestly higher average rates of recombination than those derived from unisexual crosses. Recombination hot and cold spots across the C. deneoformans genome are also identified and are associated with increased GC content. Finally, we observed regions genome-wide with allele frequencies deviating from the expected parental ratio. These findings and observations advance our quantitative understanding of the genetic events that occur during sexual reproduction in C. deneoformans, and the impact that different forms of sexual reproduction are likely to have on genetic diversity in this important fungal pathogen.

genetics↗

bioRxiv2017

The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age

Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focused on the maternal genetic makeup of the Neolithic ([~] 5500-3000 BCE), Chalcolithic ([~] 3000-2200 BCE) and Early Bronze Age ([~] 2200-1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character.

genetics↗