Viitasammakon (Rana arvalis Nilsson) populaatiogenetiikka Pohjois-Euroopassa

The ongoing climate change along with increasing levels of pollutants, diseases, habitat loss and fragmentation constitute global threats to the persistence of many populations, species and ecosystems. However, for the long-term persistence of local populations, one of the biggest threats is the intrinsic loss of genetic variation. In order to adapt to changes in the environment, organisms must have a sufficient supply of heritable variation in traits important for their fitness. With a loss of genetic variation, the risk of extinction will increase. For conservational practices, one should therefore understand the processes that shape the genetic population structure and also the broader (historical) phylogenetic patterning of the species in focus. In this thesis, microsatellite markers were applied to study genetic diversity and population differentiation of the protected moor frog (Rana arvalis) in Fennoscandia from both historical (evolutionary) and applied (conservation) perspectives. The results demonstrate that R. arvalis populations are highly structured over rather short geographic distances. Moreover, the results suggest that R. arvalis recolonized Fennoscandia from two directions after the last ice age. This has had implications for the genetic structuring and population differentiation, especially in the northernmost parts where the two lineages have met. Compared to more southern populations, the genetic variation decreases and the interpopulation differentiation increases dramatically towards north. This could be an outcome of serial population bottlenecking along the recolonization route. Also, current isolation and small population sizes increase the effect of drift, thus reinforcing the observed pattern. The same pattern can also be seen in island populations. However, though R. arvalis on the island of Gotland has lost most of its neutral genetic variability, our results indicate that the levels of additive genetic variation have remained high. This conforms to the conjecture that though neutral markers are widely used in conservation purposes, they may be quite uninformative about the levels of genetic variation in ecologically important traits. Finally, the evolutionary impact of the typical amphibian mating behaviour on genetic diversity was investigated. Given the short time available for larval development, it is important that mating takes place as early as possible. The genetic data and earlier capture-recapture data suggest that R. arvalis gather at mating grounds they are familiar with. However, by forming leks in random to relatedness, and having multiple paternities in single clutches, the risk of inbreeding may be minimized in this otherwise highly philopatric species.Ilmastonmuutos, saasteet sekä sairaudet uhkaavat monien lajien, yksittäisten populaatioiden tai kokonaisten ekosysteemien tulevaisuutta. Suurin uhka on kuitenkin elinympäristön häviäminen ja pirstoutuminen, sekä niiden aiheuttama geneettisen monimuotoisuuden väheneminen. Ilman riittävää geneettistä vaihtelua eliöiden sopeutuminen muuttuvaan elinympäristöön vaikeutuu ja riski lajin tai populaation häviämiselle kasvaa. Luonnon suojelemisen kannalta onkin siksi tärkeää ymmärtää eri lajien erityspiirteitä populaatiorakenteessa, sekä niiden historiallisia taustoja. Näin käynnissä olevien muutosten vaikutukset lajiin on mahdollista havaita tai jopa ennaltaehkäistä. Väitöskirjassa tarkastellaan uhanalaisen viitasammakon (Rana arvalis) populaatiogenetiikkaa evolutiivisesta näkökulmasta. Historian antamia tuloksia voidaan käyttää paikallisten tutkimusten tukena esimerkiksi suojelupäätöksiä tehtäessä. Väitöskirjassa osoitetaan, että viitasammakkopopulaatiot ovat geneettisesti merkittävästi erilaistuneet hyvin lyhyiden etäisyyksien ylitse. Tähän sekä geneettiseen vaihteluun vaikuttaa kuitenkin populaatioiden maantieteellinen sijainti. Pohjoismaihin laji on viime jääkauden jälkeen saapunut todennäköisesti kahdesta eri suunnasta, Suomeen idästä ja Ruotsiin etelästä päin, kohtauspaikkana Pohjois-Ruotsi. Pohjoisen alueen viitasammakkopopulaatiot ovat geneettiseltä monimuotoisuudeltaan köyhempiä ja populaatioiden väliset erot suurempia eteläisiin populaatioihin verrattuna. Nämä erot johtunevat kolonisaatiotavasta, jossa muutama yksilö on perustanut uuden populaation muiden edellä ja näin geneettinen muuntelu on vähitellen kadonnut pohjoiseen tultaessa. Myös pienissä ja eriytyneissä populaatioissa geneettinen muuntelu häviää nopeammin ja aikaansaa voimakasta erilaistumista populaatioden välillä, mikä on selvästi nähtävissä saaripopulaatioissa. Gotlannin viitasammakoista neutraali geneettinen muuntelu on radikaalisti vähentynyt. Mutta toisin kuin aikaisemmin on usein oletettu, tämä ei näytä pätevän muunteluun ekologisesti tärkeitä ominaisuuksia koodaavissa geeneissä. Väitöskirjassa pohditaan myös sammakoille tyypillisen lisääntymistavan evolutiivista merkitystä geneettiselle monimuotoisuudelle. Koska lyhyessä kesässä aikaa on vähän toukkien kehitykselle, nopea lisääntyminen on elintärkeää. Tämä saattaa selittää sen, että sammakot kerääntyvät lisääntymään tutuille paikoille kuten tutkimuksesta saatu geneettinen data ja aikaisemmin kirjattu aikuisten yksilöiden paikkauskollisuus osoittavat. Lisääntymispaikoilla koiraat kuitenkin näyttävät ryhmittyvän sattumanvaraisesti sukulaisuussuhteista riippumatta. Sisäsiittoisuuden riskejä saattaa myös minimoida yksittäisten viitasammakkonaaraiden munaklimpeissä havaittu moni-isyys

Karyotypic analysis and FISH mapping of microsatellite motifs reveal highly differentiated XX/XY sex chromosomes in the pink-tailed worm-lizard (Aprasia parapulchella, Pygopodidae, Squamata)

BACKGROUND: The infraorder Gekkota is intriguing because it contains multiple chromosomal and environmental sex determination systems that vary even among closely related taxa. Here, we compare male and females karyotypes of the pink-tailed worm-lizard (Aprasia parapulchella), a small legless lizard belonging to the endemic Australian family Pygopodidae. RESULTS: We applied comparative genomic hybridization to reveal an XX/XY sex chromosome system in which the Y chromosome is highly differentiated from the X in both gross morphology and DNA sequence. In addition, FISH mapping has revealed that two microsatellite repeat motifs, (AGAT)n and (AC)n, have been amplified multiple times on the Y chromosome. CONCLUSION: XY karyotypes are found in other pygopodids (Delma inornata and Lialis burtonis), suggesting that the common ancestor of Pygopodidae also had XY sex chromosomes. However, the morphology and size of the Y chromosomes are different among the three species, suggesting that the processes underlying the evolution of sex chromosomes in the Pygopodidae involved chromosome rearrangements and accumulation and amplification of repeats

An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access

PurposeAdvanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed 'Type 1'), but it is unclear how variant prevalences differ between AMD patients from different ethnicities.MethodsCollective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls.ResultsType 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49-53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities.ConclusionsThe relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care.Peer reviewe

Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation.

Psoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17Aind/+ , IL-17Aind/+ control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin-/luminol-based assays, respectively. Quantitative RT-PCR determined neutrophilic activity and inflammation-related markers in skin and aorta. To track skin-derived immune cells, we used PhAM-K14-IL-17Aind/+ mice allowing us to mark all cells in the skin by photoconversion of a fluorescent protein to analyze their migration into spleen, aorta, and lymph nodes by flow cytometry. Compared to controls, K14-IL-17Aind/+ mice exhibited elevated ROS levels in the skin and a higher neutrophilic oxidative burst accompanied by the upregulation of several activation markers. In line with these results psoriatic mice displayed elevated expression of genes involved in neutrophil migration (e.g., Cxcl2 and S100a9) in skin and aorta. However, no direct immune cell migration from the psoriatic skin into the aortic vessel wall was observed. Neutrophils of psoriatic mice showed an activated phenotype, but no direct cellular migration from the skin to the vasculature was observed. This suggests that highly active vasculature-invading neutrophils must originate directly from the bone marrow. Hence, the skin-vasculature crosstalk in psoriasis is most likely based on the systemic effects of the autoimmune skin disease, emphasizing the importance of a systemic therapeutic approach for psoriasis patients

Recontacting biobank participants to collect lifestyle, behavioural and cognitive information via online questionnaires : lessons from a pilot study within FinnGen

OBJECTIVES: To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform. DESIGN: Biobank-based recontacting pilot study. SETTING: Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021. PARTICIPANTS: All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s). OUTCOME MEASURES: The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies. RESULTS: The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18-69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92. CONCLUSION: In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.publishedVersionPeer reviewe

An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access

PurposeAdvanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed ‘Type 1’), but it is unclear how variant prevalences differ between AMD patients from different ethnicities.MethodsCollective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls.ResultsType 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49–53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities.ConclusionsThe relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care.</p

The first complete mitochondrial genome of Pygopodidae (Aprasia parapulchella Kluge)

The Pygopodidae comprise an enigmatic group of legless lizards endemic to the Australo-Papuan region. Here we present the first complete mitochondrial genome for a member of this family, Aprasia parapulchella, from Australia. The mitochondrial genome of A. parapulchella is 16528 base pairs long and contains 13 protein-coding genes, 22 tRNA genes, two rRNA genes and the control region, conforming to the typical vertebrate gene order. The overall mitochondrial nucleotide composition is 31.7% A, 24.5% T, 30.5% C and 13.2% G. This corresponds to a total A+T content of 56.3%, which is similar to that of other squamate lizard genomes