Bioethical issues of preventing hereditary diseases with late onset in the Sakha Republic (Yakutia)

Background: Prenatal diagnosis of congenital and hereditary diseases is a priority for the development of medical technologies in Russia. However, there are not many published research results on bioethical issues of prenatal DNA testing. Objective: The main goal of the article is to describe some of the bioethical aspects of prenatal DNA diagnosis of hereditary diseases with late onset in genetic counselling practice in the Sakha Republic (Yakutia) – a far north-eastern region of Russia. Methods: The methods used in the research are genetic counselling, invasive chorionic villus biopsy procedures, molecular diagnosis, social and demographic characteristics of patients. Results: In 10 years, 48 (76%) pregnant women from families tainted with hereditary spinocerebellar ataxia type 1 and 15 pregnant women from families with myotonic dystrophy have applied for medical and genetic counselling in order to undergo prenatal DNA testing. The average number of applications is 7–8 per year. There are differences in prenatal genetic counselling approaches. Conclusion: It is necessary to develop differentiated ethical approaches depending on the mode of inheritance, age of manifestation, and clinical polymorphism of hereditary disease

Association of SNPs of CD40 Gene with Multiple Sclerosis in Russians

<div><p>Multiple sclerosis (MS) is a serious, incurable neurological disease. In 2009, the ANZgene studies detected the suggestive association of located upstream of CD40 gene in chromosome 20q13 (p = 1.3×10⁻⁷). Identification of the causal variant(s) in the <i>CD40</i> locus leads to a better understanding of the mechanism underlying the development of autoimmune pathologies. We determined the genotypes of rs6074022, rs1883832, rs1535045, and rs11086996 in patients with MS (n = 1684) and in the control group (n = 879). Two SNPs were significantly associated with MS: rs6074022 (additive model C allele OR = 1.27, 95% CI = [1.12–1.45], <i>p</i> = 3×10⁻⁴) and rs1883832 (additive model T allele OR = 1.20, 95% CI = [1.05–1.38], <i>p</i> = 7×10⁻³). In the meta-analysis of our results and the results of four previous studies, we obtain the association <i>p</i>-value of 2.34×10⁻¹², which confirmed the association between MS and rs6074022 at a genome-wide significant level. Next, we demonstrated that the model including rs6074022 only sufficiently described the association. From our analysis, we can speculate that the association between rs1883832 and MS was induced by LD, whereas rs6074022 was a marker in stronger LD with the functional variant or was the functional variant itself. Our results indicated that the functional variants were located in the upstream region of the gene <i>CD40</i> and were in higher LD with rs6074022 than LD with rs1883832.</p></div

Logistic regression association results for SNPs of <i>CD40</i> gene with the development of MS.

<p>Abbreviations: 95% CI, 95% confidence interval; OR, odds ratio; NA, not applicable; RAF, risk allele frequency in control group; SNP, single-nucleotide polymorphism; HWE-p-value of exact test for deviation from Hardy-Weinberg equilibrium in groups; AIC–Akaike Information Criterion. Analysis was performed for four models: co-dominant, dominant, additive and recessive. Significant associations are shown in italic. The best model for each of significant associated SNPs is shown in bold.</p

LD between the SNPs <i>CD40</i> gene.

<p>According to the result of the HapMap Project (v.3). union panel for Utah residents with Northern and Western European (CEU) and Toscans in Italy (TSI). SNPs from our study are shown in red frame.</p

Meta-analysis of our results with previously published data on the association between rs6074022 and MS.

<p>Abbreviation: GenMSA (NL), GenMSA (US), GenMSA (CH), IMSGC (UK), IMSGC (US), BWH/TT, and ANZgene. In the meta-analysis the total OR for all studies was 1.17 (95% CI = 1.10–1.23) with a statistical significance of <i>p</i> = 2.24×10⁻¹². The heterogeneity test (<i>Q</i>-test) did not find significant differences between the studies (<i>χ</i>² (7) = 12.16, <i>p</i> = 0.10).</p

Ancient human genomes suggest three ancestral populations for present-day Europeans

We sequenced the genomes of a ~7,000-year-old farmer from Germany and eight ~8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes ¹⁻⁴ with 2,345 contemporary humans to show thatmost present-day Europeans derive from atleast three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians³, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages

Ancient human genomes suggest three ancestral populations for present day Europeans

We sequenced genomes from a $\sim$7,000 year old early farmer from Stuttgart in Germany, an $\sim$8,000 year old hunter-gatherer from Luxembourg, and seven $\sim$8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations' deep relationships and show that EEF had $\sim$44% ancestry from a "Basal Eurasian" lineage that split prior to the diversification of all other non-African lineages