RESUMO
The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country.
Assuntos
Variação Genética , Adulto , Doenças Transmissíveis/genética , Demografia , Haplótipos , Humanos , Mutação INDEL , Farmacogenética , Fenótipo , Filogeografia , Polimorfismo de Nucleotídeo Único , Federação Russa/etnologia , Seleção Genética , Sequenciamento Completo do GenomaRESUMO
Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = -0.81); most patients with low-medium (39-55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39-55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow's index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.
Assuntos
Ataxina-1/genética , Aptidão Genética , Seleção Genética , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Coeficiente de Natalidade , Estudos de Coortes , Feminino , Heterozigoto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mutação , Sibéria/epidemiologiaRESUMO
Viliuisk encephalomyelitis (VE) is a neurodegenerative disease that afflicts aboriginal people of Yakutia in Siberia with unknown etiology. Oligoclonal IgG bands (OCBs) were discovered in the VE patients (Green et al., 2003). In this study we analysed the association of OCBs with clinical symptoms in 58 VE patients. Positive oligoclonal IgG are associated with a shorter duration of disease (p=0.002), older age of onset (p=0.023) and high frequency of main neurological VE symptoms such as dementia, frontal dysbasia, bulbar disorders, muscle atrophy and centrally caused pelvic disorders. Our results show that the OCBs in VE patients are associated with more severe central nervous system (CNS) damage and may cause secondary complications in the course of the disease.