Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

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.

Discrimination power of Investigator DIPplex loci in Finnish and Somali populations.

In this study, the suitability of the Investigator DIPplex insertion/deletion polymorphism (indel) kit for forensic casework was assessed through the genotyping of 151 Finns and 175 Somalis. Allele frequency and heterozygosity (H) of this 30-indel marker set were determined, and forensic efficacy was evaluated through estimation of discrimination power (DP), match probability (MP), typical paternity index (TPI), power of paternity exclusion (PE), and polymorphic information content (PIC). A high level of discrimination power was observed for the marker set in both sample groups (CDP>0.9999). East-west population substructure found previously in uniparental markers within Finland was not evident for this autosomal set (E-W F(ST)=0.003). High exclusion probability and low subdivision together demonstrate that these markers are well-suited for identification of individuals in Finland. However, values for typical paternity index and power of paternity exclusion were low (TPI range Finns=0.750-1.190, PE=0.996; TPI Somalis=0.680-1.090, PE=0.986) in comparison to standard STR sets, and thus indels are not recommended for use in paternity or kinship investigations, except as a supplement to other more powerful tools.

Post-mortem ABCB1 genotyping reveals an elevated toxicity for female digoxin users.

BACKGROUND: P-glycoprotein, a common transporter molecule, is known to affect metabolic functions in humans. Polymorphisms of the multidrug resistance gene (ABCB1/MDR1) coding for P-glycoprotein have been linked to changes in the processing of several commonly used medications in patients. Here, we have evaluated the impact of ABCB1 single nucleotide polymorphisms on digoxin fatality, through investigation of the relationship between post-mortem digoxin concentration and ABCB1 genotype. METHODS: The effect of three ABCB1 single nucleotide polymorphisms (SNPs) (3435C>T, 1236C>T, and 2677G>T) on digoxin concentration was examined in 112 deceased Finnish subjects through RT-PCR genotyping of post-mortem blood samples. These subjects were selected on the basis of digoxin findings during the post-mortem toxicology screen, and categorized by digoxin concentration into three distinct groups. The distributions of mutant alleles and haplotypes in the deceased were compared to a random sample of 143 Finns. RESULTS: Mutant genotype frequencies showed a positive relationship with post-mortem digoxin concentration for all SNPs. Female subjects showed a more emphatic pattern, suggesting a higher risk of digoxin intoxication. CONCLUSIONS: These findings demonstrate a link between ABCB1 polymorphisms and increased mortality, and suggest that individualized genotyping should be considered prior to digoxin treatment. This research also exemplifies the value of gender-segregated genotyping studies in helping establish drug safety parameters, while allowing more decisive determination of cause and manner of death in a medico-legal context.