Mutations in the lipase member H (LIPH) gene cause autosomal recessive hypotrichosis with woolly hair. We report herein on five consanguineous families from Pakistan segregating hypotrichosis and woolly hair. Genetic investigation using polymorphic microsatellite markers revealed homozygosity for a region spanning the HYPT7 locus on chromosome 3 in affected individuals of all five families. Sequence analysis of the LIPH gene revealed a novel nonsense mutation (p.Arg260X) associated with hypotrichosis without woolly hair in one family. In the remaining four families we identified previously described mutations in a homozygous state in affected members. These findings extend the spectrum of known LIPH mutations in the Pakistani population.

The rhizosphere is a critical microenvironment that plays key roles in plant nutrient availability, largely due to root interactions with rhizospheric microbes. However, we lack suitable methods that can elucidate mechanisms determining rhizospheric community structure and function within the context of a dynamic, undisturbed soil. Microdialysis has been used for low intrusive soil nutrient sampling at the scale of a fine root, with small probes that also enable release of defined compounds. We evaluated whether microdialysis could simulate exudation, by the release of sucrose, and stimulate changes in a soil microbial community, allowing us to determine the microbes that responded most to carbon release. Microdialysis successfully stimulated growth on probe surfaces of fungi and bacteria, which were extracted and sequenced for identification. Microbial growth was also visualized with scanning electron microscopy. The majority of the species stimulated were classified as fast growing or opportunistic, e.g. yeasts, moulds, proteobacteria and actinobacteriota, which are known to respond quickly (within days) to the release of simple sugars as exudates in the rhizosphere. The study demonstrates the potential of using microdialysis as a tool to investigate interactions between root exudation and soil microbial community composition, initially for individual compounds and in the future for more complex compositions.

Bicuspid aortic valve, a prevalent congenital malformation, predisposes individuals to severe complications. Although the condition exhibits substantial heritability, known protein-coding and common regulatory mutations explain a minority of cases. To assess the contribution of rare regulatory variants, here we integrate high-resolution three-dimensional genome organization profiling with matched whole-genome sequencing from eight individuals with bicuspid aortic valves and eight with standard tricuspid aortic valves. In bicuspid aortic valve patients, mutation-driven chromatin rewiring affected 1.8-fold more valve development genes than in healthy individuals. Genome-wide in silico analyses show that rare regulatory mutations disrupt the transcriptomes of mesenchymal cell populations necessary for endocardial cushion formation. We identify 198 candidate genes associated with bicuspid aortic valve, revealing pronounced heterogeneity and complex interplay between coding and regulatory mutations. Collectively, our findings establish rare regulatory mutations as contributors to the heritability of bicuspid aortic valve and underscore the need to elucidate their mechanistic roles in disease pathogenesis.

The blue antelope (Hippotragus leucophaeus) is the only large African mammal species to have become extinct in historical times, yet no nuclear genomic information is available for this species. A recent study showed that many alleged blue antelope museum specimens are either roan (Hippotragus equinus) or sable (Hippotragus niger) antelopes, further reducing the possibilities for obtaining genomic information for this extinct species. While the blue antelope has a rich fossil record from South Africa, climatic conditions in the region are generally unfavorable to the preservation of ancient DNA. Nevertheless, we recovered two blue antelope draft genomes, one at 3.4× mean coverage from a historical specimen (∼200 years old) and one at 2.1× mean coverage from a fossil specimen dating to 9,800-9,300 cal years BP, making it currently the oldest paleogenome from Africa. Phylogenomic analyses show that blue and sable antelope are sister species, confirming previous mitogenomic results, and demonstrate ancient gene flow from roan into blue antelope. We show that blue antelope genomic diversity was much lower than in roan and sable antelope, indicative of a low population size since at least the early Holocene. This supports observations from the fossil record documenting major decreases in the abundance of blue antelope after the Pleistocene-Holocene transition. Finally, the persistence of this species throughout the Holocene despite low population size suggests that colonial-era human impact was likely the decisive factor in the blue antelope's extinction.

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

Rice cultivation on paddy soil is commonly associated with emissions of methane, a greenhouse gas, but rice varieties may differ in their actual level of emissions. This study analysed methane emissions associated with 22 distinct rice genotypes, using gas chromatography, and identified the cultivar Heijing 5 from northern China as a potential low-methane rice variety. To confirm this and to examine whether Heijing 5 can perform similarly at higher latitudes, Heijing 5 was cultivated in field trials in China (lat. 32° N) and Sweden (lat. 59° N) where (i) methane emissions were measured, (ii) methanogen abundance in the rhizosphere was determined using quantitative PCR, and (iii) the concentrations of nutrients in water and of heavy metals in rice grain and paddy soil were analysed. The results demonstrated that the low-methane rice cultivar Heijing 5 can successfully complete an entire growth period at high-latitude locations such as central Sweden. Massively parallel sequencing of mRNAs identified candidate genes involved in day length and cold acclimatisation. Cultivation of Heijing 5 in central Sweden was also associated with relatively low heavy metal accumulation in rice grains and lowered nutrient losses to neighbouring water bodies.

Nitrogen can be taken up by trees in the form of nitrate, ammonium and amino acids, but the influence of the different forms on tree growth and development is poorly understood in angiosperm species like Populus. We studied the effects of both organic and inorganic forms of nitrogen on growth and wood formation of hybrid aspen trees in experimental conditions that allowed growth under four distinct steady-state nitrogen levels. Increased nitrogen availability had a positive influence on biomass accumulation and the radial dimensions of both xylem vessels and fibers, and a negative influence on wood density. An optimal level of nitrogen availability was identified where increases in biomass accumulation outweighed decreases in wood density. None of these responses depended on the source of nitrogen except for shoot biomass accumulation, which was stimulated more by treatments complemented with nitrate than by ammonium alone or the organic source arginine. The most striking difference between the nitrogen sources was the effect on lignin composition, whereby the abundance of H-type lignin increased only in the presence of nitrate. The differential effect of nitrate is possibly related to the well-known role of nitrate as a signaling compound. RNA-sequencing revealed that while the lignin-biosynthetic genes did not significantly (FDR <0.01) respond to added NO3 - , the expression of several laccases, catalysing lignin polymerization, was dependent on N-availability. These results reveal a unique role of nitrate in wood formation and contribute to the knowledge basis for decision-making in utilizing hybrid aspen as a bioresource.