Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.
BackgroundThe date palm is one of the oldest cultivated fruit trees. It is critical in many ways to cultures in arid lands by providing highly nutritious fruit while surviving extreme heat and environmental conditions. Despite its importance from antiquity, few genetic resources are available for improving the productivity and development of the dioecious date palm. To date there has been no genetic map and no sex chromosome has been identified.ResultsHere we present the first genetic map for date palm and identify the putative date palm sex chromosome. We placed ~4000 markers on the map using nearly 1200 framework markers spanning a total of 1293 cM. We have integrated the genetic map, derived from the Khalas cultivar, with the draft genome and placed up to 19% of the draft genome sequence scaffolds onto linkage groups for the first time. This analysis revealed approximately ~1.9 cM/Mb on the map. Comparison of the date palm linkage groups revealed significant long-range synteny to oil palm. Analysis of the date palm sex-determination region suggests it is telomeric on linkage group 12 and recombination is not suppressed in the full chromosome.ConclusionsBased on a modified gentoyping-by-sequencing approach we have overcome challenges due to lack of genetic resources and provide the first genetic map for date palm. Combined with the recent draft genome sequence of the same cultivar, this resource offers a critical new tool for date palm biotechnology, palm comparative genomics and a better understanding of sex chromosome development in the palms.
The date palm tree is a commercially important member of the genus Phoenix whose 14 species are dioecious with separate male and female individuals. To identify sex determining genes we sequenced the genomes of 15 female and 13 male Phoenix trees representing all 14 species. We identified male-specific sequences and extended them using phased single-molecule sequencing or BAC clones. We observed that only four genes contained sequences conserved in all analyzed Phoenix males. Most of these sequences showed similarity to a single genomic locus in the closely related monoecious oil palm. CYP703 and GPAT3, two single copy genes present in males and critical for male flower development in other monocots, were absent in females. A LOG-like gene appears translocated into the Y-linked region and is suggested to play a role in suppressing female flowers. Our data are consistent with a two-mutation model for the evolution of dioecy in Phoenix.
The date palm (Phoenix dactylifera L.) is one of the oldest cultivated trees and is intimately tied to the history of human civilization. There are hundreds of commercial cultivars with distinct fruit shapes, colors, and sizes growing mainly in arid lands from the west of North Africa to India. The origin of date palm domestication is still uncertain, and few studies have attempted to document genetic diversity across multiple regions. We conducted genotyping-by-sequencing on 70 female cultivar samples from across the date palm–growing regions, including four Phoenix species as the outgroup. Here, for the first time, we generate genome-wide genotyping data for 13,000–65,000 SNPs in a diverse set of date palm fruit and leaf samples. Our analysis provides the first genome-wide evidence confirming recent findings that the date palm cultivars segregate into two main regions of shared genetic background from North Africa and the Arabian Gulf. We identify genomic regions with high densities of geographically segregating SNPs and also observe higher levels of allele fixation on the recently described X-chromosome than on the autosomes. Our results fit a model with two centers of earliest cultivation including date palms autochthonous to North Africa. These results adjust our understanding of human agriculture history and will provide the foundation for more directed functional studies and a better understanding of genetic diversity in date palm.
The date palm tree is a commercially important member of the genus Phoenix whose 14 species are all dioecious with separate male and female individuals.Previous studies identified a multi-megabase region of the date palm genome linked to sex and showed that dioecy likely developed in Phoenix prior to speciation. To identify genes critical to sex determination we sequenced the genomes of 28 Phoenix trees representing all 14 species. Male-specific sequences were identified and extended using phased single molecule sequencing or BAC clones to distinguish X and Y alleles.Here we show that only four genes contain sequences conserved in all analyzed males, likely identifying the changes foundational to dioecy in Phoenix. The majority of these sequences show similarity to a single genomic locus in the closely related oil palm. CYP703 and GPAT3, two genes critical to male flower development in other monocots, appear fully deleted in females while maintained as single copy in males. A LOG-like gene appears translocated into the Y chromosome and a cytidine deaminase-like appears at the border of a chromosomal rearrangement. Our data supports a two-mutation model for the evolution from hermaphroditism to dioecy through a gynodioecious intermediate. Phoenix sex determinationPage nr. 3 of 26
Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.
Background The date palm is one of the oldest cultivated fruit trees. The tree can withstand high temperatures and low water and the fruit can be stored dry offering nutrition across the year. The first region of cultivation is believed to be near modern day Iraq, however, where and if the date palm was domesticated is still a topic of debate. Recent studies of chloroplast and genomic DNA revealed two major subpopulations of cultivars centered in both the Eastern range of date palm cultivation including Arabian Peninsula, Iraq and parts of South Asia, and the Western range, including North Africa. Results To better understand the origins of date palm cultivation we sequenced and analyzed over 200 mitochondrial and chloroplast genomes from a geographically diverse set of date palms. Here we show that, based on mitochondrial and chloroplast genome-wide genotyping data, the most common cultivated date palms contain 4 haplotypes that appear associated with geographical region of cultivar origin. Conclusions These data suggest at least 3 and possibly 4 original maternal contributions to the current date palm population and doubles the original number. One new haplotype was found mainly in Tunisia, Algeria and Egypt and the second in Iraq, Iran and Oman. We propose that earliest date palm cultivation occurred independently in at least 3 distinct locations. This discovery will further inform understanding of the history and origins of cultivated date palm. Electronic supplementary material The online version of this article (10.1186/s12864-019-5834-7) contains supplementary material, which is available to authorized users.
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