Genomic identification in the historical case of the Nicholas II royal family.

Accurate unambiguous identification of ancient or historical specimens can potentially be achieved by DNA analysis. The controversy surrounding the fate of the last Russian Emperor, Nicholas II, and his family has persisted, in part, because the bodies of 2 children, Prince Alexei and 1 of his sisters, have not been found. A grave discovered in 1991 contained remains putatively identified as those of the Russian Royal family. However, not all family members were represented. Here, we report the results of genomic analyses of new specimens, the human remains of 2 burned skeletons exhumed from a grave discovered in July 2007, and the results of a comprehensive genomic analysis of remains from the 1991 discovery. Additionally, approximately 117 years old archival blood specimens from Nicholas II were obtained and genotyped, which provided critical material for the specific determination of individual identities and kinship identifications. Results of genotypic analyses of damaged historical specimens were evaluated alongside samples from descendants of both paternal and maternal lineages of the European Royal families, and the results conclusively demonstrate that the recently found remains belong to children of Nicholas II: Prince Alexei and his sister. The results of our studies provide unequivocal evidence that the remains of Nicholas II and his entire family, including all 5 children, have been identified. We demonstrate that convergent analysis of complete mitochondrial genome sequences combined with nuclear DNA profiles is an efficient and conclusive method for individual and kinship identification of specimens obtained from old historic relics.

Ethnic differences in the serotonin transporter polymorphism (5-HTTLPR) in several European populations.

The serotonin transporter (5-HTT) is a protein that has a major role in divergent psychiatric disorders, personality traits and behaviors, by regulating serotonergic synaptic function. Transcriptional activity of the 5-HTT gene (5-HTT or SLC6A4) is modulated by a polymorphic repetitive element (5-HTT gene-linked polymorphic region, 5-HTTLPR), which consists of a 44-base pairs insertion-deletion in the promoter region, creating a short (S) allele and a long (L) allele. Ethnic differences in the allele frequencies of the 5-HTTLPR exist between Caucasian and Asian populations. This study investigated ethnic differences in 5-HTTLPR in 1804 healthy Caucasian subjects from several European populations living in Croatia and the Russian Federation. The genotype and allele frequency of the 5-HTTLPR differed significantly (P<0.001) between male and female Croats, Russians, Tatars and Bashkirs, due to the lower frequency of the S allele (38% and 37%) and S/S genotype (14% and 15%) in Croat men and women compared to other studied groups. When male and female data were collapsed, Russians had marginally different allele and genotype distribution compared to Bashkirs and Tatars. Bashkirs and Tatars had similar allele and genotype frequency. The higher frequency of the S/S genotype was found in Tatars and Bashkirs compared to Croats and Russians. Gender related differences occurred only in the allele distribution within Bashkir population. These ethnic differences might be responsible for the inconsistent findings in the studies of the association between various psychiatric disorders, personality traits, behaviors and 5-HTTLPR across different ethnicities, and should be controlled to enable the generalization of results across various population groups.

Genotype analysis identifies the cause of the "royal disease".

The "royal disease," a blood disorder transmitted from Queen Victoria to European royal families, is a striking example of X-linked recessive inheritance. Although the disease is widely recognized to be a form of the blood clotting disorder hemophilia, its molecular basis has never been identified, and the royal disease is now likely extinct. We identified the likely disease-causing mutation by applying genomic methodologies (multiplex target amplification and massively parallel sequencing) to historical specimens from the Romanov branch of the royal family. The mutation occurs in F9, a gene on the X chromosome that encodes blood coagulation factor IX, and is predicted to alter RNA splicing and to lead to production of a truncated form of factor IX. Thus, the royal disease is the severe form of hemophilia, also known as hemophilia B or Christmas disease.

Polymorphisms of the serotonin transporter gene (5-HTTLPR, A/G SNP in 5-HTTLPR, and STin2 VNTR) and their relation to personality traits in healthy individuals from Russia.

OBJECTIVE: Numerous studies have reported association of the serotonin transporter gene (5-HTT) polymorphisms and neuroticism and traits characterizing sociability and activity. This study aimed to define a single genotype effect of three polymorphic markers in the 5-HTT gene (5-HTTLPR, A/G SNP in 5-HTTLPR and STin2 VNTR) and to check possible association of the 5-HTT haplotypes and personality traits [assessed with Eysenck Personality Inventory (EPI) and Temperament and Character Inventory (TCI) questionnaires] in 301 healthy young individuals. METHODS: To investigate single genotype and haplotype effects of all polymorphic markers, multivariate analysis of variance and haplotype trend regression analyses were conducted correspondingly. RESULTS: Individuals with STin2.10 allele scored significantly lower on Neuroticism (EPI) (P=0.007) and Harm Avoidance (P=0.005) in the overall sample. The same pattern of association was reported in women: carriers of STin2.10 allele scored lower on Harm Avoidance (TCI) (P=0.008). Haplotype trend regression analyses revealed that carriers of S12 haplotype had lower sociability-related traits such as Extraversion (EPI) and Novelty Seeking (TCI), whereas Harm Avoidance (TCI) (anxiety-related trait) was higher. Opposite association was observed for S10 haplotype: Extraversion (EPI) score was higher, whereas Harm Avoidance (TCI) score was lower in carriers of this haplotype. CONCLUSION: As single polymorphism effect of STin2 was observed in relation to anxiety-related traits, opposite S10 and S12 haplotype effects on Neuroticism and Harm Avoidance could be explained by the larger impact of STin2 polymorphism. Controversially, we consider that the variance in sociability-related traits is related to specific haplotypes of 5-HTT gene.