Complex Genetic Interactions between Piwi and HP1a in the Repression of Transposable Elements and Tissue-Specific Genes in the Ovarian Germline

Insertions of transposable elements (TEs) in eukaryotic genomes are usually associated with repressive chromatin, which spreads to neighbouring genomic sequences. In ovaries of Drosophila melanogaster, the Piwi-piRNA pathway plays a key role in the transcriptional silencing of TEs considered to be exerted mostly through the establishment of H3K9me3 histone marks recruiting Heterochromatin Protein 1a (HP1a). Here, using RNA-seq, we investigated the expression of TEs and the adjacent genomic regions upon Piwi and HP1a germline knockdowns sharing a similar genetic background. We found that the depletion of Piwi and HP1a led to the derepression of only partially overlapping TE sets. Several TEs were silenced predominantly by HP1a, whereas the upregulation of some other TEs was more pronounced upon Piwi knockdown and, surprisingly, was diminished upon a Piwi/HP1a double-knockdown. We revealed that HP1a loss influenced the expression of thousands of protein-coding genes mostly not adjacent to TE insertions and, in particular, downregulated a putative transcriptional factor required for TE activation. Nevertheless, our results indicate that Piwi and HP1a cooperatively exert repressive effects on the transcription of euchromatic loci flanking the insertions of some Piwi-regulated TEs. We suggest that this mechanism controls the silencing of a small set of TE-adjacent tissue-specific genes, preventing their inappropriate expression in ovaries.

Diversity And Population Structure of Nordic Potato Cultivars and Breeding Clones Grown Under Long Daylength in Europe

The genetic diversity and population structure of breeding germplasm is central knowledge for crop improvement. To gain insight into the genetic potential of the germplasm used for potato breeding in a Nordic breeding program as well as the collections from the Nordic genebank (NordGen), 133 potato genotypes were genotyped using the Infinium Illumina 20K SNP array. After SNP filtering, 11 610 polymorphic SNPs were included in the analysis. In addition, data from three important breeding traits – percent dry matter and uniformity of tuber shape and eye – were scored to measure the variation be-tween groups. The genetic diversity among the genotypes was estimated using principal coordinate analysis based on the genetic distance between individuals, as well as by using the software STRUC-TURE. Both methods suggest that the collected breeding material and the germplasm from the gene-bank are closely related, with a low degree of population structure between the groups. The phenotypic distribution among the genotypes revealed significant differences, especially between farmer’s cultivars and released cultivars and breeding clones. The percent heterozygosity was similar between the groups, with a mean average of 58–60%. Overall, the breeding germplasm and the collection of genotypes from the Nordic gene bank seems to be closely related with similar genetic background. This gains insight that the genetic potential of available Nordic potato breeding germplasm is low, and for genetic hybridi-zation purposes, genotypes from outside the Nordic region should be employed.

Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5−/− Mice

Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (Alox5-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid oxygenase activity. Here we characterized the polyenoic fatty acid metabolism of these mice in more detail and tested the animals in three different experimental inflammation models. In experimental autoimmune encephalomyelitis (EAE), Alox5-KI mice displayed an earlier disease onset and a significantly higher cumulative incidence rate than wildtype controls but the clinical score kinetics were not significantly different. In dextran sodium sulfate-induced colitis (DSS) and in the chronic constriction nerve injury model (CCI), Alox5-KI mice performed like wildtype controls with similar genetic background. These results were somewhat surprising since in previous loss-of-function studies targeting leukotriene biosynthesis (Alox5−/− mice, inhibitor studies), more severe inflammatory symptoms were observed in the EAE model but the degree of inflammation in DSS colitis was attenuated. Taken together, our data indicate that these mutant Alox5-KI mice respond differently in two models of experimental inflammation than Alox5−/− animals tested previously in similar experimental setups.

SARS-CoV-2 under an elimination strategy in Hong Kong

Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity.

Hypertrophic Cardiomyopathy and Primary Restrictive Cardiomyopathy: Similarities, Differences and Phenocopies

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These “sarcomeric cardiomyopathies” also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy. To further complicate this scenario some infiltrative (amyloidosis) and storage diseases (Fabry disease and glycogen storage diseases) may show either a hypertrophic or restrictive phenotype according to left ventricular wall thickness and filling pattern. Establishing a correct etiological diagnosis among HCM, primary RCM, and hypertrophic or restrictive phenocopies is of paramount importance for cascade family screening and therapy.

Concordant acute myeloblastic leukemia in identical twins treated with allogeneic transplantation from a younger HLA-identical sibling following a single apheresis procedure

A concordant leukemia is that which occurs in a pair of monozygotic twins; a similar genetic background suggests an in utero monoclonal origin. We present the case of a pair of monozygotic infants with concordant acute myeloid leukemia who underwent a peripheral blood hematopoietic stem-cell transplant (HSCT) from a single, younger human leukocyte antigen-identical sibling donor, using a fractioned graft collected during only one apheresis procedure. Twin A relapsed at +456 and received a second haploidentical HSCT from his father, twin B has been in complete remission since the first HSCT. Both children are in complete remission and with negative minimal residual disease at +900 (after second transplant) and +1488, respectively.

Does Functionality Condition the Population Structure and Genetic Diversity of Endangered Dog Breeds under Island Territorial Isolation?

Despite the undefinition of the origins of Ca de Rater (CR) and Ca de Bestiar (CB) dogs, references to these endangered autochthonous breeds highlighted their ratting/pet and shepherding/guard skills for centuries. Genealogical historical records were traced back to founders. Founder number in the reference population (146 and 53 for CR and CB, respectively), historical and reference maximum generations traced (eight and seven for CR and CB, respectively), and historical average number of complete generations (1.04 for both breeds) were determined. Structure assessment revealed the existence of subpopulations regarding criteria such as breeders (75 and 17), breeder location (32 and eight), owners (368 and 198), and owner location (73 and 51) for CR and CB, respectively. Average inbreeding (F) within breed subpopulations ranged from 0.27–1.20% for CB breeders and the rest of subpopulation criteria for both breeds, respectively, except for CB owners and owner location. F ranged from 0.27–1.41% for CB historical population and CR current population, respectively. The study of genetic diversity revealed a relatively similar genetic background between subpopulations. Average coancestry between and within breeds suggested a similar evolutionary process. However, Mann–Whitney U test determined significant differences for diversity parameters (F, ΔR, coancestry, nonrandom mating degree, maximum, complete, and equivalent generations, ΔF, and genetic conservation index) between breeds and their functionalities. Conclusively, functionality in dog breeds may determine the genetic diversity evolution of endangered breeds, even when these share the same geographic isolation conditions.

Characterizing the metabolites related to rice salt tolerance with introgression lines exhibiting contrasting performances in response to saline conditions

Rice is susceptible to salt stress at the seedling stage. To explore the molecular mechanisms underlying salt tolerance, the metabolic responses to salt stress were investigated with a metabolite-profiling technique. Gas chromatography–mass spectrometry was used to profile metabolite changes in five rice lines with a similar genetic background, but with obviously diverse growth performances under saline conditions. A total of 84 metabolites were detected in rice leaf extracts under control and saline conditions. The data revealed that amino acids were enriched more in three salt-tolerant lines (G58, G1710, and IR64) than in two salt-sensitive lines (G45 and G52) under control conditions, suggesting that there were basal metabolite differences between the tolerant and sensitive lines. Additionally, significantly higher allantoin levels in G58, G1710, and IR64 under both stress and control conditions were observed, implying allantoin was important for the better growth of the three rice lines. Moreover, sorbitol, melezitose, and pipecolic acid levels increased considerably in response to salt stress in the five lines, indicating they contribute to rice responses to salt stress significantly. Interestingly, the similar metabolic patterns were regulated by salt stress in the salt-sensitive and salt-tolerant lines, and the main difference was quantitative. The sensitive lines had more pronounced increases during the early stages of the stress treatment than the tolerant lines. Thus, monitoring the metabolome changes of plants may provide crucial insights into how plants tolerate stress. The results presented herein provide valuable information for further elucidating the molecular mechanisms underlying rice salt tolerance.

Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background

Primary plasma cell leukemia (pPCL) is a highly aggressive plasma cell dyscrasia characterised by short remissions and very poor survival. Although the 17p deletion is associated with poor outcome and extramedullary disease in MM, its presence does not confer the degree of aggressiveness observed in pPCL. The comprehensive exploration of isoform expression and RNA splicing events may provide novel information about biological differences between the two diseases. Transcriptomic studies were carried out in nine newly diagnosed pPCL and ten MM samples, all of which harbored the 17p deletion. Unsupervised cluster analysis clearly distinguished pPCL from MM samples. In total 3584 genes and 20033 isoforms were found to be deregulated between pPCL and MM. There were 2727 significantly deregulated isoforms of non-differentially expressed genes. Strangely enough, significant differences were observed in the expression of spliceosomal machinery components between pPCL and MM, in respect of the gene, isoform and the alternative splicing events expression. In summary, transcriptome analysis revealed significant differences in the relative abundance of isoforms between pPCL and MM, even when they both had the 17p deletion. The mRNA processing pathway including RNA splicing machinery emerged as one of the most remarkable mechanisms underlying the biological differences between the two entities.

A Transcriptomic Study of the Tail Fat Deposition in Two Types of Hulun Buir Sheep According to Tail Size and Sex

Hulun Buir sheep of similar genetic background were divided into two lines based on tail types: Small- and big fat-tailed. To explore the molecular mechanism of fat deposition in sheep tails, we firstly evaluated the morphology and transcription level differences of tail fat between these two lines. RNA-Seq technology was used to identify differentially expressed genes (DEGs) in phenotypic extremes of tail sizes. Five comparisons were performed taking into account two factors, sex and tail type. We screened out 373 DEGs between big-tailed and small-tailed Hulun Buir sheep, and 775 and 578 DEGs between two types of tails in male and female sheep, respectively. The results showed an obvious sex difference in the fat metabolism in sheep based on gene ontology (GO), pathway, and network analyses. Intriguingly, there were two different co-expression networks only respectively shown in male and female sheep, which were insulin-related network acting on upstream pathways and PPARG-related network effect in downstream pathways. Furthermore, these two networks were linked by a classic pathway of regulating adipogenesis. This is the first study to investigate the sex differences of fat metabolism in domestic animals, and it demonstrates a new experimental way to study fat metabolism. Our findings will provide theoretical background in understanding the tail-size phenotype in sheep and can be exploited in breeding small-tailed sheep.