Elisabet Einarsdottir

Developmental dyslexia (DD) is a heritable reading disorder characterized by phonological deficits. Still, the mechanisms through which genetic susceptibility influence early literacy development and speech sound processing remain unclear. This longitudinal study investigated associations between DD susceptibility genes and the development of pre-reading skills and neural speech discrimination between two and five years of age. We studied 159 children, most with familial risk of DD. Genetic susceptibility to DD was determined through six single nucleotide variants in the genes DYX1C1, DCDC2, KIAA0319, ROBO1, NCAN, and NRSN1, as well as an unweighted polygenic risk score across these variants capturing cumulative genetic burden. Pre-reading skills were assessed using a behavioral test battery, whereas neural speech discrimination was studied by recording event-related potentials to speech-sound changes.Individual genetic variants were associated with pre-reading abilities already at two years. Variants in DCDC2 and ROBO1 were linked to serial naming, whereas variants in DYX1C1, NRSN1, and ROBO1 were associated with auditory short-term memory. Variants in NCAN and DCDC2 were associated with reduced mismatch negativity (MMN) amplitudes at both two and five years. A higher polygenic risk was associated with reduced MMN and late discriminative negativity amplitudes at two years. Overall, this study suggests that genetic susceptibility mediated by at least five of the identified DD susceptibility genes influences both neural speech processing and cognitive precursors of reading since early childhood. It supports the view that DD is a neurodevelopmental condition with early-emerging biological signatures, and highlights mismatch responses as a potential neurophysiological endophenotype for DD.

Background: The malfunction of paravertebral muscles may contribute to the development of idiopathic scoliosis. Several candidate genes have been linked to scoliosis, but the underlying mechanisms and cell types remain unclear. Methods: We included 40 idiopathic scoliosis cases and 19 controls. Muscle biopsies were obtained bilaterally in the cases, and at least unilaterally in the controls. RNA sequencing, differential gene expression analysis and gene set enrichment analysis were performed between cases and controls, and between convex and concave sides in the cases. Hounsfield units (HU) in paravertebral muscles from preoperative CT were assessed at biopsy sites in cases. Results: Qualified transcriptome analysis included 56 samples (30 convex, 26 concave) from 35 scoliosis cases and 22 samples from 17 controls. Among 14,212 expressed genes included in the downstream analysis, 22 differentially expressed genes were identified between cases and controls and 16 between convex and concave sides. Scoliosis cases showed decreased fetal muscle and immune cells. Convex side showed decreased fibro-adipogenic progenitors, endothelial cell types, satellite cells and myeloid cells and increased fetal skeletal muscle cells. Morphological asymmetry was verified by the HU findings. Conclusion: These results indicated asymmetry of gene expression profiles and suggests a fetal developmental origin of idiopathic scoliosis, with increased muscle mass pushing convexity.

The SMARTer®Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian kit from Takara®(SMARTer Pico) has proved successful and reliable in generating stranded RNA Illumina libraries from degraded total RNA and ultra-low input amounts of total RNA below detection level. Here we attempted to streamline and simplify the library prep protocol at the key fragmentation step bottleneck. Our key findings were that reduced fragmentation times neither affect the depletion efficiency, nor the library complexity. Skipping the fragmentation resulted in longer libraries when examined in the capillary electrophoresis but this was compensated for during sequencing, as long fragments are less likely to form clusters during sequencing. Skipping the fragmentation also affected the gene body coverage, where a bias to the 5' end was observed though this compromised neither the data quality, complexity nor reproducibility. Additionally, using 16 PCR cycles seems to have little effect on the library complexity. Overall, we can see that sample input is the key to library complexity and reproducibility, while fragmentation time has less impact on data.

How species adapt to diverse environmental conditions is essential for understanding evolution and the maintenance of biodiversity. The European cisco (Coregonus albula) is a salmonid that occurs in both fresh and brackish water, and this together with the presence of sympatric spring‐ and autumn‐spawning lacustrine populations provides an opportunity for studying the genetics of adaptation in relation to salinity and timing of reproduction. Here, we present a high‐quality reference genome of the European cisco based on PacBio HiFi long read sequencing and HiC‐directed scaffolding. We generated low‐coverage whole‐genome sequencing data from 336 individuals across 12 population samples to explore population structure and genetics of ecological adaptation. We found a major subdivision between two groups of populations most likely reflecting colonisation from different glacial refugia. Within the two major groups, we detected further genetic differentiation between spring‐ and autumn‐spawning populations and between populations from freshwater lakes, rivers and brackish water (Bothnian Bay). A genome‐wide screen for genetic differentiation among populations identified a set of outlier SNPs strongly correlated with spawning timing and salinity. Several of the genes associated with spawning time, including BHLHE40, TIMELESS and CPT1A, have previously been shown to have a role in circadian rhythm biology. As many as 17 loci were associated with genetic differentiation between populations reproducing in fresh and brackish water. This study provides insights into the genomic basis of ecological adaptation in European cisco with implications for sustainable fishery management.

The European green toad (Bufotes viridis) is geographically widely distributed. While the species global conservation status is labeled as of least concern by the IUCN, it is declining in many parts of its range where populations are fragmented and isolated. A high-quality reference genome is an important resource for conservation genomic researchers who are trying to understand and interpret the genomic signals of population decline, inbreeding, and the accumulation of deleterious mutations. Here, we assembled and annotated a chromosome-level reference genome for B. viridis as part of the European Reference Genome Atlas pilot project. The genome assembly, with a size of ∼3.89 Gb consists of 11 chromosomes and an additional 2,096 unplaced scaffolds. The final assembly had a scaffold N50 value of 478.39 Mb and covered 90.4% single copy tetrapod orthologs, and 46.7% repetitive elements. Finally, a total of 23,830 protein-coding genes matching a known gene, together with 56,974 mRNAs were predicted. This high-quality reference genome will benefit amphibian evolutionary genomics research and enable conservation genetic studies to inform practical conservation work on this species.

Introduction: Back pain is common in idiopathic scoliosis. The aim of this study was to study known genetic variants associated with pain in individuals with idiopathic scoliosis. Methods: We included 1442 individuals with juvenile or adolescent idiopathic scoliosis from Sweden and Denmark. Single nucleotide variants (SNV) genotyping was performed on 37 SNVs. Pain was assessed using 2 questionnaires. The mean pain domain score on the Scoliosis Research Society 22 revised questionnaire (SRS-22r) ranging between 1 (worst) and 5 (best) was dichotomized into a “back pain group” (score P-values ranging between 0.08 to 0.99 and 0.08 to 0.95. Conclusion: This study suggests that known genetic variants associated with pain do not play a significant role in the development of pain in individuals with idiopathic scoliosis.

The early evolution of sex chromosomes has remained obscure for more than a century. The Vandiemenella viatica species group of morabine grasshoppers is highly suited for studying the early stages of sex chromosome divergence and degeneration of the Y chromosome. This stems from the fact that neo‐XY sex chromosomes have independently evolved multiple times by X‐autosome fusions with different autosomes. Here, we generated new chromosome‐level assemblies for two chromosomal races representing karyotypes with and without neo‐sex chromosomes (P24XY and P24X0), and sequence data of a third chromosomal race with a different neo‐XY chromosome system (P25XY). Interestingly, these two neo‐XY chromosomal races are formed by different X‐autosome fusions (involving chr1 and chrB, respectively), and we found that both neo‐Y chromosomes have partly ceased to recombine with their neo‐X counterpart. We show that the neo‐XY chromosomes have diverged through accumulation of SNPs and structural mutations, and that many neo‐Y‐linked genes have degenerated since recombination ceased. However, the non‐recombining regions of neo‐Y chromosomes host non‐degenerated genes crucial for sex determination, such as sex‐lethal and transformer, alongside genes associated with spermatogenesis, fertility, and reproduction, illustrating their integrative role as a masculinizing supergene. Contrary to expectations, the neo‐Y chromosomes showed (slightly) lower density of transposable elements (TEs) compared to other genomic regions. The study reveals the unique dynamics of young sex chromosomes, with evolution of recombination suppression and pronounced decay of (some) neo‐sex chromosome genes, and provides a compelling case illustrating how chromosomal fusions and post‐fusion mutational processes contribute to the evolution of supergenes.

Morabine grasshoppers in the Vandiemenella viatica species group, which show karyotype diversity, have been studied for their ecological distribution and speciation in relation to their genetic and chromosomal diversity. They are good models for studying sex chromosome evolution as “old” and newly emerged sex chromosomes co-exist within the group. Here we present a reference genome for the viatica19 chromosomal race, that possesses the ancestral karyotype within the group. Using PacBio HiFi and Hi-C sequencing, we generated a chromosome-level assembly of 4.09 Gb in span, scaffold N50 of 429 Mb, and complete BUSCO score of 98.1%, containing 10 pseudo-chromosomes. We provide Illumina datasets of males and females, used to identify the X chromosome. The assembly contains 19,034 predicted protein-coding genes, and a total of 75.21% of repetitive DNA sequences. By leveraging HiFi reads, we mapped the genome-wide distribution of methylated bases (5mC and 6 mA). This comprehensive assembly offers a robust reference for morabine grasshoppers and supports further research into speciation and sex chromosome diversification within the group and its related species.

Background: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in childhood. We set out to investigate the effects of a 20‐week exercise intervention on whole‐blood transcriptome profile (RNA‐seq) in children with overweight/obesity.Methods: Twenty‐four children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20‐week exercise program (intervention group; n = 10), or to a no‐exercise control group (n = 14). Whole‐blood transcriptome profile was analyzed using RNA‐seq by STRT technique with GlobinLock technology.Results: Following the 20‐week exercise intervention program, 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p‐value 0.05). Genes enriched in GO processes and molecular pathways showed different immune response in boys (antigen processing and presentation, infections, and T cell receptor complex) and in girls (Fc epsilon RI signaling pathway) (FDR <0.05).Conclusion: These results suggest that 20‐week exercise intervention program alters the molecular pathways involved in immune processes in children with overweight/obesity.

Purpose: Idiopathic scoliosis is the most common spinal deformity and affects 1–3% of children and adolescents. Idiopathic scoliosis may run in families and the purpose of this systematic review was to describe the degree of heritability. Methods: We searched Medline, Web of Science and EMBASE for family and twin studies reporting heritability estimates for idiopathic scoliosis, or studies from which heritability estimates could be calculated. Reference lists were screened for additional papers. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered at PROSPERO (registration number: CRD42022307329). Results: The literature search identified 1134 reports. After full-text screening, nine eligible reports were included for data extraction. Seven were twin studies containing between 5 and 526 pairs, and two were family studies with 1149 and 2732 individuals, respectively. Quality was ‘good’ in four studies and ‘fair’ in five studies. In general, studies with radiograph-confirmed diagnosis reported higher heritability estimates than studies with self-reported diagnosis. Population-based twin studies reported lower heritability estimates than clinic-based twin studies. Family-based studies reported higher heritability estimates than twin studies. Pairwise concordance for scoliosis ranged from 0.11 to 1.00 in monozygotic twins and from 0 to 1.0 in dizygotic twins. A meta-analysis of three studies resulted in a narrow sense heritability estimate of 0.57 (95% CI: 0.29–0.86). Conclusion: Twin and family studies indicate a hereditary component in idiopathic scoliosis, but study heterogeneity is large, and the degree of the heritability is uncertain. Nevertheless, known genetic variants associated with idiopathic scoliosis can still only explain a minor part of heritability.