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Fragmentation of isolated populations increases the risk of inbreeding and loss of genetic diversity. The endemic Saimaa ringed seal (Pusa hispida saimensis) is one of the most endangered pinnipeds in the world with a population of only ~ 400 individuals. The current genetic diversity of this subspecies, isolated in Lake Saimaa in Finland for ca. 1000 generations, is alarmingly low. We performed whole-genome sequencing on Saimaa ringed seals (N = 30) and analyzed the level of homozygosity and genetic composition across the individual genomes. Our results show that the Saimaa ringed seal population has a high number of runs of homozygosity (RoH) compared with the neighboring Baltic ringed seal (Pusa hispida botnica) reference population (p

Depression is known to be a risk factor for suicide. Currently, the most used antidepressants are selective serotonin reuptake inhibitors (SSRIs). Not all users, however, benefit from them. In such cases, treatment failure can be explained in part by genetic differences. In this study, we investigated the role of pharmacogenetic factors in citalopram-positive completed suicides (n = 349). Since citalopram is metabolized by CYP2C19 and CYP2D6 enzymes, the study population was genotyped for clinically relevant CYP2C19 and CYP2D6 polymorphisms and CYP2D6 copy number variation. To assess genetic differences between suicide cases and Finns in general, Finnish population samples (n = 855) were used as controls. Also, the role of drug interactions among suicide cases was evaluated. We found enrichment of a combined group of genetically predicted poor and ultrarapid metabolizer phenotypes (gMPs) of CYP2C19 among suicide victims compared to controls 0.356 [0.31-0.41] vs. 0.265 [0.24-0.30] (p = 0.0065). In CYP2D6 gMPs, there was no difference between cases and controls when the study population was analyzed as a whole. However, there were significantly more poor metabolizers among females who committed suicide by poisoning compared to female controls. In 8% of all drug poisoning deaths, lifetime drug-drug interaction was evaluated having a contribution to the fatal outcome. From clinical perspective, pharmacogenetic testing prior to initiation of SSRI drug could be beneficial. It may also be useful in medico-legal settings as it may elucidate obscure poisoning cases. Also, the possibility of unintentional drug interactions should be taken into account in drug poisoning deaths.

Diabetes and alcohol abuse may cause severe metabolic disturbances that can be fatal. These may be difficult to diagnose in autopsies based solely on macroscopical and histological findings. In such cases, metabolic markers, such as postmortem glucose and ketone levels, can provide supporting information. Glucose or combined glucose and lactate, the Traub value, is often used to indicate hyperglycemia. The use of the Traub value, however, has been questioned by some, because the lactate levels are known to elevate in postmortem samples also due to other reasons than glycolysis of glucose molecules. Ketoacidosis can be detected by analyzing ketone body levels, especially beta-hydroxybutyric acid (BHB). Acetone is also elevated in severe cases of ketoacidosis. Here, we have evaluated the value of these biomarkers for postmortem determination of the metabolic disturbances. Retrospective data of 980 medico-legal autopsies performed in Finland, where glucose, lactate and ketone bodies were analyzed, was collected. Our findings show that the Traub value indicates hyperglycemia, even when glucose levels are low. For diagnosis, evaluation of complementing markers, e.g. ketone bodies and glycated hemoglobin is needed. Our results show that BHB can be used for screening and diagnosis of ketoacidosis. Acetone alone is not sufficient, since it is elevated only in the most severe cases. We also found that alcohol abuse rarely causes severe ketoacidosis. However, sporadic cases do exist where ketone body levels are extremely high. Despite this, alcoholic ketoacidosis is very rarely diagnosed as the cause of death.

Molecular-genetic assessments of demographic history, population structure, and loss of genetic variation in small natural populations are often hampered by a lack of information on initial diversity, isolation time, and migration rates. The landlocked population of currently less than 300 ringed seals inhabiting Lake Saimaa in southeastern Finland offers a unique model for studying these questions in small populations. It has remained completely isolated since the last ice age, information on its initial genetic diversity can be inferred from the large marine source population in the Baltic Sea, and its ecology is well studied. We analyzed the mitochondrial DNA diversity of 215 Saimaa ringed seals spanning three decades in order to assess long- and short-term changes in the gene pool of this critically endangered subspecies. The mtDNA diversity of the Saimaa ringed seal is low, consisting of only eight haplotypes. Nevertheless, coalescent simulations show that the diversity is unexpectedly high when contrasted with the over 800 generations of isolation and the estimated historical carrying capacity of the lake. In the short term, marked temporal and spatial differentiation was observed among three decades and four regions of Lake Saimaa, suggesting extremely low effective subpopulation sizes and limited migration of females within the lake. Our study strongly suggests that enhancing gene flow and population growth is crucial for maintaining the remaining genetic diversity of the Saimaa ringed seal.

The Finnish population in Northern Europe has been a target of extensive genetic studies during the last decades. The population is considered as a homogeneous isolate, well suited for gene mapping studies because of its reduced diversity and homogeneity. However, several studies have shown substantial differences between the eastern and western parts of the country, especially in the male-mediated Y chromosome. This divergence is evident in non-neutral genetic variation also and it is usually explained to stem from founder effects occurring in the settlement of eastern Finland as late as in the 16th century. Here, we have reassessed this population historical scenario using Y-chromosomal, mitochondrial and autosomal markers and geographical sampling covering entire Finland. The obtained results suggest substantial Scandinavian gene flow into south-western, but not into the eastern, Finland. Male-biased Scandinavian gene flow into the south-western parts of the country would plausibly explain the large inter-regional differences observed in the Y-chromosome, and the relative homogeneity in the mitochondrial and autosomal data. On the basis of these results, we suggest that the expression of 'Finnish Disease Heritage' illnesses, more common in the eastern/north-eastern Finland, stems from long-term drift, rather than from relatively recent founder effects.

The Y-chromosomal diversity among Finnish males is characterized by low diversity and substantial geographical substructuring. In a 12-locus data set (PowerPlexY), espe-cially the eastern parts of the country showed low levels of variation, and the western, middle, and eastern parts of Finland differed from each other by their Y-short tandem repeat (STR) haplotype frequencies (Palo et al., Forensic Sci Int Genet 1:120–124, 2007). In this paper, we have analyzed geographical patterns of Y-STR diversity using both 12-locus (PowerPlexY) and 17-locus (Yfiler) data sets from the same set of geographically structured samples. In the larger data set, the haplotype diversity is significantly higher, as expected. The geographical distribution of haplotypes is similar in both data sets, but the level of interregional differences is significantly lower in the Yfiler data. The implications of these observations on the forensic casework are discussed.

Northwest Siberia is geographically remote territory, which has been settled by indigenous human populations probably since the Upper Paleolithic. To investigate the genetic landscape of Northwest Siberians, we have analyzed mitochondrial and Y chromosome DNA polymorphisms of 169 unrelated individuals from Khanty and Mansi ethnic groups in Northwest Siberia. In addition, HVS-I sequences (N = 3522) and Y chromosome SNP data (N = 2175), obtained from the literature, were used to elucidate the genetic relationships among the North Eurasian populations. The results show clinal distributions of mtDNA and Y chromosome haplogroups along East-West axis of Northern Eurasia. In this context, the Ugric-speaking Khanty and Mansi appear as unique intermediate populations carrying Upper Paleolithic and more recent haplotypes typical for both West and East Eurasian gene pools. This admixture indicates that the Khanty and Mansi populations have resided in the contact zone of genetically distinguishable eastern and western Eurasia.

The Lake Saimaa ringed sealPhoca hispida saimensis has lived as anisolated landlocked population in easternFinland since the early post-glacial. In thelast century, the population crashed down to c.200 individuals, and is under a constant threatof extinction. We evaluated the genetic historyof the Saimaa population through a comparisonwith the conspecific sister populations in theArctic Ocean and the Baltic Sea, which haveretained high levels of variation since thedeglaciation. At eight microsatellite loci, thecurrent gene diversity (heterozygosity) of theSaimaa seal was 69% lower than in thereference populations. Allowing reasonablemutation rates (μ = 10−4), thisimplies a long-term post-glacial effectivepopulation size of Ne ≃ 350,and a slow average rate of inbreeding ΔF≃ 0.15% per generation during the c.860 generations (9 500 years) of isolation. Thecurrent Ne is an order of magnitudesmaller and ΔF correspondinglylarger. Whereas the additional loss of markervariation in the short term will not be highrelative to that already taken place, it seemsunwarranted to suppose that the past, slowinbreeding would have effectively purged thepopulation of genetic load and reduced thegenetic risks from small population size.Although the population is now clearlygeographically subdivided in the complex lakesystem, we found little genetic differentiationbetween main breeding areas (FST =0.02). However, at the current low populationdensities, the subdivision may markedly furtherincrease the future rate of inbreeding.

Interest in long-term population size monitoring programmes of amphibians has recently been fuelled by the global decline of their populations (Alford and Richards 1999; Houlahan et al. 2000). Many of these ongoing monitoring schemes are based on spawn clump counts, which can be used to approximate local female population sizes (e.g. Loman 1996). However, these estimations can be hampered by the difficulty to distinguish spawn clumps of some closely related and co-existing species. For instance, in Rana temporaria (the common frog) and R. arvalis (the moor frog) – which occur in sympatry through much of Europe – species identification based on spawn clump characteristics (e.g. size and appearance of clump and eggs) is not 100% reliable and even experienced herpetologists may have to leave up to 15% of the egg clusters unidentified (e.g. Loman 2001, p. 3). We became particularly aware of this problem in the course of population genetic studies of these two species after discovering that samples collected by an experienced herpetologist frequently did not show the expected DNA banding patterns. Here, we present a simple PCR-RFLP method for species identification of R. arvalis and R. temporaria that can be used to pre-screen samples if the species identity is in question. Our method will also be useful for monitoring studies of small and declining R. arvalis populations of Central Europe (Gasc et al. 1997), where even small errors in species identification can be of particular concern. DNA was extracted from one egg (the Karelian and Estonian samples) or app. 4–8 mm3 piece of muscle tissue (other samples, Table 1) using standard SDS – proteinase K digestion treatment followed by NaCl extraction and isopropanol precipitation (e.g. Bruford et al. 1992). A 605-bp Cytb segment was amplified Table 1. R. arvalis and R. temporaria samples analysed

Background Factors affecting the success of short tandem repeat (STR) amplification of poorly preserved samples are generally known, but as of yet, they have seldom been systematically assessed. Using two different maximum likelihood-based methods, the relative importance of DNA quantity, degradation and inhibition in STR genotyping was studied with DNA extracts from a set of old bone samples. First, the effects of different factors related to PCR amplification were estimated with a generalized linear mixed model. Second, error rates of allelic drop-out and drop-in were estimated on the basis of the frequency and nature of mismatches between replicates. Results In autosomal STR analyses, the most important factor was the DNA quantity, followed by the degradation, whereas in Y-chromosomal STR analysis, the most important factor was the degradation. Inhibition was a minor concern in STR analyses of poorly preserved bones. Conclusions The success of PCR amplification depends largely on the template DNA quality (amount and degradation), but these problems can be partly compensated for by different primer design and amplification chemistry. Consequently, the relative roles of the compromising factors differ according to the kit used.