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Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis’ potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidum in early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood., Current Biology, 30 (19), ISSN:0960-9822, ISSN:1879-0445

Levanluhta is a unique archaeological site with the remains of nearly a hundred Iron Age individuals found from a water burial in Ostrobothnia, Finland. The strongest climatic downturn of the Common Era, resembling the great Fimbulvinter in Norse mythology, hit these people during the 6th century AD. This study establishes chronological, dietary, and livelihood synthesis on this population based on stable carbon and nitrogen isotopic and radiocarbon analyses on human remains, supported by multidisciplinary evidence. Extraordinarily broad stable isotopic distribution is observed, indicating three subgroups with distinct dietary habits spanning four centuries. This emphasizes the versatile livelihoods practiced at this boundary of marine, freshwater, and terrestrial ecosystems. While the impact of the prolonged cold darkness of the 6th century was devastating for European communities relying on cultivation, the broad range of livelihoods provided resilience for the Levanluhta people to overcome the abrupt climatic decline.

In Europe, modern mitochondrial diversity is relatively homogeneous and suggests an ubiquitous rapid population growth since the Neolithic revolution. Similar patterns also have been observed in mitochondrial control region data in Finland, which contrasts with the distinctive autosomal and Y-chromosomal diversity among Finns. A different picture emerges from the 843 whole mitochondrial genomes from modern Finns analyzed here. Up to one third of the subhaplogroups can be considered as Finn-characteristic, i.e. rather common in Finland but virtually absent or rare elsewhere in Europe. Bayesian phylogenetic analyses suggest that most of these attributed Finnish lineages date back to around 3,000–5,000 years, coinciding with the arrival of Corded Ware culture and agriculture into Finland. Bayesian estimation of past effective population sizes reveals two differing demographic histories: 1) the ‘local’ Finnish mtDNA haplotypes yielding small and dwindling size estimates for most of the past; and 2) the ‘immigrant’ haplotypes showing growth typical of most European populations. The results based on the local diversity are more in line with that known about Finns from other studies, e.g., Y-chromosome analyses and archaeology findings. The mitochondrial gene pool thus may contain signals of local population history that cannot be readily deduced from the total diversity.

Preeclampsia is a common vascular disease of pregnancy with genetic predisposition. Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely understood. In this study, we determined the potential linkage of severe preeclampsia to the most central complement gene, C3. Three cohorts of Finnish patients and controls were recruited for a genetic case-control study. Participants were genotyped using Sequenom genotyping and Sanger sequencing. Initially, we studied 259 Finnish patients with severe preeclampsia and 426 controls from the Southern Finland preeclampsia and the Finnish population based preeclampsia cohorts. We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. Following the primary screening, C3 was selected as the candidate gene and consequently Sanger sequenced. Fourteen SNPs from C3 were also genotyped by a Sequenom panel in 960 patients with severe preeclampsia and 705 controls, including already sequenced individuals. Three of the 43 SNPs observed within C3 were associated with severe preeclampsia: rs2287845 (p=0.038, OR=1.158), rs366510 (p=0.039, OR=1.158), and rs2287848 (p=0.041, OR=1.155). We also discovered 16 SNP haplotypes with extreme linkage disequilibrium in the middle of the gene with a protective (p=0.044, OR=0.628) or a predisposing (p=0.011, OR=2.110) effect to severe preeclampsia depending on the allele combination. Genetic variants associated with preeclampsia are located in key domains of C3 and could thereby influence the function of C3. This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant preeclampsia subphenotype, severe preeclampsia. The result highlights a potential role for the complement system in the pathogenesis of preeclampsia and may help in defining prognostic and therapeutic subgroups of preeclamptic women.

A rare hereditary mechanobullous disorder called epidermolysis bullosa (EB) causes blistering in the skin and the mucosal membranes. To date, nineteen EB-related genes have been discovered in human and other species. We describe here a novel EB variant in dogs. Two newborn littermates of Central Asian Shepherd dogs with severe signs of skin blistering were brought to a veterinary clinic and euthanized due to poor prognosis. In post-mortem examination, the puppies were shown to have findings in the skin and the mucosal membranes characteristic of EB. A whole-genome sequencing of one of the affected puppies was performed to identify the genetic cause. The resequencing data were filtered under a recessive model against variants from 31 other dog genomes, revealing a homozygous case-specific nonsense variant in one of the known EB-causing genes, COL7A1 (c.4579C> T, p.R1527*). The variant results in a premature stop codon and likely absence of the functional protein in the basement membrane of the skin in the affected dogs. This was confirmed by immunohistochemistry using a COL7A1 antibody. Additional screening of the variant indicated full penetrance and breed specificity at similar to 28% carrier frequency. In summary, this study reveals a novel COL7A1 variant causing recessive dystrophic EB and provides a genetic test for the eradication of the disease from the breed.

The axon guidance receptor, Robo1, controls the pathfinding of callosal axons in mice. To determine whether the orthologous ROBO1 gene is involved in callosal development also in humans, we studied polymorphisms in the ROBO1 gene and variation in the white matter structure in the corpus callosum using both structural magnetic resonance imaging and diffusion tensor magnetic resonance imaging. We found that five polymorphisms in the regulatory region of ROBO1 were associated with white matter density in the posterior part of the corpus callosum pathways. One of the polymorphisms, rs7631357, was also significantly associated with the probability of connections to the parietal cortical regions. Our results demonstrate that human ROBO1 may be involved in the regulation of the structure and connectivity of posterior part of corpus callosum.

It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe.

Music perception and practice represent complex cognitive functions of the human brain. Recently, evidence for the molecular genetic background of music related phenotypes has been obtained. In order to further elucidate the molecular background of musical phenotypes we analyzed genome wide copy number variations (CNVs) in five extended pedigrees and in 172 unrelated subjects characterized for musical aptitude and creative functions in music. Musical aptitude was defined by combination of the scores of three music tests (COMB scores): auditory structuring ability, Seashores test for pitch and for time. Data on creativity in music (herein composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Several CNVRs containing genes that affect neurodevelopment, learning and memory were detected. A deletion at 5q31.1 covering the protocadherin-α gene cluster (Pcdha 1-9) was found co-segregating with low music test scores (COMB) in both sample sets. Pcdha is involved in neural migration, differentiation and synaptogenesis. Creativity in music was found to co-segregate with a duplication covering glucose mutarotase gene (GALM) at 2p22. GALM has influence on serotonin release and membrane trafficking of the human serotonin transporter. Interestingly, genes related to serotonergic systems have been shown to associate not only with psychiatric disorders but also with creativity and music perception. Both, Pcdha and GALM, are related to the serotonergic systems influencing cognitive and motor functions, important for music perception and practice. Finally, a 1.3 Mb duplication was identified in a subject with low COMB scores in the region previously linked with absolute pitch (AP) at 8q24. No differences in the CNV burden was detected among the high/low music test scores or creative/non-creative groups. In summary, CNVs and genes found in this study are related to cognitive functions. Our result suggests new candidate genes for music perception related traits and supports the previous results from AP study.