BACKGROUND: The Slavs are a major ethnolinguistic group of Europe, yet the process that led to their formation remains disputed. As of the sixth century CE, people supposedly belonging to the Slavs populated the space between the Avar Khaganate in the Carpathian Basin, the Merovingian Frankish Empire to the West and the Balkan Peninsula to the South. Proposed theories to explain those events are, however, conceptually incompatible, as some invoke major population movements while others stress the continuity of local populations. RESULTS: We report high-quality genomic data of 18 individuals from two nearby burial sites in South Moravia that span from the fifth to the tenth century CE, during which the region became the core of the ninth century Slavic principality. In contrast to existing data, the individuals reported here can be directly connected to an Early-Slavic-associated culture and include the earliest known inhumation associated with any such culture. CONCLUSIONS: The data indicates a strong genetic shift incompatible with local continuity between the fifth and seventh century, supporting the notion that the Slavic expansion in South Moravia was driven by population movement.

• MeSH
• History, Ancient MeSH
• Genome, Human * MeSH
• Humans MeSH
• Human Migration MeSH
• Genetics, Population * MeSH
• DNA, Ancient * analysis   MeSH
• Check Tag
• History, Ancient MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Names of Substances
• DNA, Ancient * MeSH

Familial clustering, twin concordance, and identification of high- and low-penetrance cancer predisposition variants support the idea that there are families that are at a high to moderate excess risk of cancer. To what extent there may be families that are protected from cancer is unknown. We wanted to test genetically whether cancer-free families share fewer breast, colorectal, and prostate cancer risk alleles than the population at large. We addressed this question by whole-genome sequencing (WGS) of 51 elderly cancer-free individuals whose numerous (ca. 1000) family members were found to be cancer-free ('cancer-free families', CFFs) based on face-to-face interviews. The average coverage of the 51 samples in the WGS was 42x. We compared cancer risk allele frequencies in cancer-free individuals with those in the general population available in public databases. The CFF members had fewer loss-of-function variants in suggested cancer predisposition genes compared to the ExAC data, and for high-risk cancer predisposition genes, no pathogenic variants were found in CFFs. For common low-penetrance breast, colorectal, and prostate cancer risk alleles, the results were not conclusive. The results suggest that, in line with twin and family studies, random environmental causes are so dominant that a clear demarcation of cancer-free populations using genetic data may not be feasible.

• Keywords
• high-risk genes, polygenic risk, predisposing genes, random environment,
• Publication type
• Journal Article MeSH

The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657del5 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657del5 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657del5 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the 'Slavic people'. We surmise that the higher fertility of female c.657del5 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2.

• MeSH
• Genetic Carrier Screening MeSH
• Adult MeSH
• Founder Effect * MeSH
• Haplotypes MeSH
• Nuclear Proteins genetics   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation * MeSH
• DNA Repair MeSH
• DNA Damage MeSH
• Cell Cycle Proteins genetics   MeSH
• Reproduction genetics   MeSH
• Nijmegen Breakage Syndrome ethnology   genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Slovakia MeSH
• Names of Substances
• Nuclear Proteins MeSH
• NBN protein, human MeSH Browser
• Cell Cycle Proteins MeSH

Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is nowadays spread across the entire continent. L2 movements were previously postulated to be related to the Bantu expansion, but L2 expansions eastwards probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new complete sequences) we provide insights on the complex net of within-African migrations in the last 60 thousand years (ka). Results show that lineages in Southern Africa cluster with Western/Central African lineages at a recent time scale, whereas, eastern lineages seem to be substantially more ancient. Three moments of expansion from a Central African source are associated to L2: (1) one migration at 70-50 ka into Eastern or Southern Africa, (2) postglacial movements (15-10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last 5 ka. The complementary population and L0a phylogeography analyses indicate no strong evidence of mtDNA gene flow between eastern and southern populations during the later movement, suggesting low admixture between Eastern African populations and the Bantu migrants. This implies that, at least in the early stages, the Bantu expansion was mainly a demic diffusion with little incorporation of local populations.

• MeSH
• Black People genetics   history   MeSH
• History, 15th Century MeSH
• History, 16th Century MeSH
• History, 17th Century MeSH
• History, 18th Century MeSH
• History, 19th Century MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• History, Medieval MeSH
• Emigration and Immigration history   MeSH
• Haplotypes genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• DNA, Mitochondrial genetics   history   MeSH
• Evolution, Molecular MeSH
• Molecular Sequence Data MeSH
• Base Sequence MeSH
• Check Tag
• History, 15th Century MeSH
• History, 16th Century MeSH
• History, 17th Century MeSH
• History, 18th Century MeSH
• History, 19th Century MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• History, Medieval MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Africa, Central MeSH
• Africa, Eastern MeSH
• Names of Substances
• DNA, Mitochondrial MeSH