Biology subjects

Rasmussen, M.

Publications and source records attributed to Rasmussen, M..

25 records · Page 2Linked to original sources

bioRxiv2021

FIND-IT: Ultrafast mining of genome diversity

Novel crop improvement methodologies, including the exploitation of natural genetic variation, are urgently required to feed our rapidly growing human population in the context of global climate change. Here we describe a Fast Identification of Nucleotide variants by DigITal PCR (FIND-IT) method for the rapid identification of pre-targeted genetic variants or rare alleles in large genomic populations. Libraries of 500,000 individuals can be screened and desired variants isolated within two weeks. FIND-IT is widely applicable for mining valuable diversity in any genomic population, including elite breeding and wild germplasm collections. The method provides single nucleotide resolution that has been validated by identifying and isolating knockout lines, non-synonymous codon changes and variants of miRNA and transcription factor binding sites in the agronomically important crop barley. In contrast to existing methods, FIND-IT does not require transformation, cloning or enzymatic steps, and is exempt from GMO regulations. Thus, FIND-IT can be applied immediately to elite crop cultivars and can be tailored to minimize or eliminate time-consuming backcrossing requirements.

genetics↗

bioRxiv2021

Infection, recovery and re-infection of farmed mink with SARS-CoV-2

Mink, on a farm with about 15,000 animals, became infected with SARS-CoV-2. Over 75% of tested animals were positive for SARS-CoV-2 RNA in throat swabs and 100% of tested animals were seropositive. The virus responsible had a deletion of nucleotides encoding residues H69 and V70 within the spike protein gene. The infected mink recovered and after free-testing of the mink, the animals remained seropositive. During follow-up studies, after a period of more than 2 months without virus detection, over 75% of tested animals scored positive again for SARS-CoV-2 RNA. Whole genome sequencing showed that the virus circulating during this re-infection was most closely related to the virus identified in the first outbreak on this farm but additional sequence changes had occurred. Animals had much higher levels of anti-SARS-CoV-2 antibodies after re-infection than at free-testing. Thus, following recovery from an initial infection, seropositive mink rapidly became susceptible to re-infection by SARS-CoV-2. Article Summary LineFollowing widespread infection with SARS-CoV-2 of mink on a farm, all tested animals had seroconverted and the farm was then tested free of infection; however, less than 3 months later, a further round of infection affected more than 75% of tested animals.

microbiology↗

bioRxiv2020

A systematic, unbiased mapping of CD8+ and CD4+ T cell epitopes in Yellow Fever vaccinees

1.Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e. immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of 1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, 2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, 3) generation of peptide-HLA tetramers to identify T cell epitopes, and 4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g. SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.

immunology↗

bioRxiv2020

An atlas of cell types in the mammalian epididymis and vas deferens

Following spermatogenesis in the testis, mammalian sperm continue to mature over the course of approximately 10 days as they transit a long epithelial tube known as the epididymis. The epididymis is comprised of multiple segments/compartments that, in addition to concentrating sperm and preventing their premature activation, play key roles in remodeling the protein, lipid, and RNA composition of maturing sperm. In order to understand the complex roles for the epididymis in reproductive biology, we generated a single cell atlas of gene expression from the murine epididymis and vas deferens. We recovered all the key cell types of the epididymal epithelium, including principal cells, clear cells, and basal cells, along with associated support cells that include fibroblasts, smooth muscle, macrophages and other immune cells. Moreover, our data illuminate extensive regional specialization of principal cell populations across the length of the epididymis, with a substantial fraction of segment-specific genes localized in genomic clusters of functionally-related genes. In addition to the extensive region-specific specialization of principal cells, we find evidence for functionally-specialized subpopulations of stromal cells, and, most notably, two distinct populations of clear cells. Analysis of ligand/receptor expression reveals a network of potential cellular signaling connections, with several predicted interactions between cell types that may play roles in immune cell recruitment and other aspects of epididymal function. Our dataset extends on existing knowledge of epididymal biology, and provides a wealth of information on potential regulatory and signaling factors that bear future investigation.

developmental biology↗

bioRxiv2019

Life history genomic regions explain differences in Atlantic salmon marine diet specialization

O_LIAnimals employ various foraging strategies along their ontogeny to acquire energy, and with varying degree of efficiencies, to support growth, maturation and subsequent reproduction events. Individuals that can efficiently acquire energy early are more likely to mature at an earlier age, as a result of faster energy gain which can fuel maturation and reproduction. C_LIO_LIWe aimed to test the hypothesis that heritable resource acquisition variation that co-varies with efficiency along the ontogeny would influence maturation timing of individuals. C_LIO_LITo test this hypothesis, we utilized Atlantic salmon as a model which exhibit a simple, hence trackable, genetic control of maturation age. We then monitored the variation in diet acquisition (quantified as the stomach fullness and composition) of individuals with different ages, and linked it genomic regions (haploblocks) that were previously identified to be associated with age-at-maturity. C_LIO_LIConsistent with the hypothesis, we demonstrated that one of the life history genomic regions tested (six6) was indeed associated with age-dependent differences in stomach fullness. Prey composition was marginally linked to both genomic regions (six6 and vgll3). We further showed Atlantic salmon switched to the so-called "feast and famine" strategy along the ontogeny, where older age groups exhibited heavier stomach content, but that came at the expense of running on empty more often. C_LIO_LIThese results suggest genetic variation underlying resource utilization variation may explain the genetic basis of age structure in Atlantic salmon. Given that ontogenetic diet has a genetic component and the strong spatial diversity associated with these genomic regions, we predict populations with diverse maturation age will have diverse evolutionary responses to future changes in marine food-web structures. C_LI

ecology↗

bioRxiv2017

Neolithization of North Africa involved the migration of people from both the Levant and Europe

The extent to which prehistoric migrations of farmers influenced the genetic pool of western North Africans remains unclear. Archaeological evidence suggests the Neolithization process may have happened through the adoption of innovations by local Epipaleolithic communities, or by demic diffusion from the Eastern Mediterranean shores or Iberia. Here, we present the first analysis of individuals genome sequences from early and late Neolithic sites in Morocco, as well as Early Neolithic individuals from southern Iberia. We show that Early Neolithic Moroccans are distinct from any other reported ancient individuals and possess an endemic element retained in present-day Maghrebi populations, confirming a long-term genetic continuity in the region. Among ancient populations, Early Neolithic Moroccans are distantly related to Levantine Natufian hunter-gatherers ([~]9,000 BCE) and Pre-Pottery Neolithic farmers ([~]6,500 BCE). Although an expansion in Early Neolithic times is also plausible, the high divergence observed in Early Neolithic Moroccans suggests a long-term isolation and an early arrival in North Africa for this population. This scenario is consistent with early Neolithic traditions in North Africa deriving from Epipaleolithic communities who adopted certain innovations from neighbouring populations. Late Neolithic ([~]3,000 BCE) Moroccans, in contrast, share an Iberian component, supporting theories of trans-Gibraltar gene flow. Finally, the southern Iberian Early Neolithic samples share the same genetic composition as the Cardial Mediterranean Neolithic culture that reached Iberia [~]5,500 BCE. The cultural and genetic similarities of the Iberian Neolithic cultures with that of North African Neolithic sites further reinforce the model of an Iberian migration into the Maghreb.\n\nSIGNIFICANCE STATEMENTThe acquisition of agricultural techniques during the so-called Neolithic revolution has been one of the major steps forward in human history. Using next-generation sequencing and ancient DNA techniques, we directly test if Neolithization in North Africa occurred through the transmission of ideas or by demic diffusion. We show that Early Neolithic Moroccans are composed of an endemic Maghrebi element still retained in present-day North African populations and distantly related to Epipaleolithic communities from the Levant. However, late Neolithic individuals from North Africa are admixed, with a North African and a European component. Our results support the idea that the Neolithization of North Africa might have involved both the development of Epipaleolithic communities and the migration of people from Europe.

genetics↗

bioRxiv2016

Ancient individuals from the North American Northwest Coast reveal 10,000 years of regional genetic continuity

Recent genome-wide studies of both ancient and modern indigenous people of the Americas have shed light on the demographic processes involved during the first peopling. The Pacific northwest coast proves an intriguing focus for these studies due to its association with coastal migration models and genetic ancestral patterns that are difficult to reconcile with modern DNA alone. Here we report the genome-wide sequence of an ancient individual known as \"Shuka Kaa\" (\"Man Ahead of Us\") recovered from the On Your Knees Cave (OYKC) in southeastern Alaska (archaeological site 49-PET-408). The human remains date to approximately 10,300 cal years before present (BP). We also analyze low coverage genomes of three more recent individuals from the nearby coast of British Columbia dating from approximately 6075 to 1750 cal years BP. From the resulting time series of genetic data, we show that the Pacific Northwest Coast exhibits genetic continuity for at least the past 10,300 cal BP. We also infer that population structure existed in the late Pleistocene of North America with Shuka Kaa on a different ancestral line compared to other North American individuals (i.e., Anzick-1 and Kennewick Man) from the late Pleistocene or early Holocene. Despite regional shifts in mitochondrial DNA haplogroups we conclude from individuals sampled through time that people of the northern Northwest Coast belong to an early genetic lineage that may stem from a late Pleistocene coastal migration into the Americas.\n\nSignificance StatementThe peopling of the Americas has been examined on the continental level with the aid of single-nucleotide polymorphism arrays, next generation sequencing, and advancements in ancient DNA, all of which have helped elucidate major population movements. Regional paleogenomic studies, however, have received less attention and may reveal a more nuanced demographic history. Here we present genomewide sequences of individuals from the northern Northwest Coast covering a time span of ~10,000 years and show that continental patterns of demography do not necessarily apply on the regional level. In comparison with existing paleogenomic data, we demonstrate that geographically linked population samples from the Northwest Coast exhibit an early ancestral lineage and find that population structure existed among Native North American groups as early as the late Pleistocene.

genomics↗