Molecular Anthropology in the genomic era

Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium ''Classification and Human Evolution'' ( 1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the approach from the genetic to the genomic level. In this framework, the meeting "DNA Polymorphisms in Human Populations: Molecular Anthropology in the Genomic Era" ( Rome, December 3-5, 2009) offered an opportunity for discussion among scholars from different disciplines, while paying attention to the impact of recent methodological innovations. Here we present an overview of the meeting and discuss perspectives and prospects of Molecular Anthropology in the genomic era

Insights into the demographic history of african pygmies from complete mitochondrial genomes

Pygmy populations are among the few hunter-gatherers currently living in sub-Saharan Africa and are mainly represented by two groups, Eastern and Western, according to their current geographical distribution. They are scattered across the Central African belt and surrounded by Bantu-speaking farmers, with whom they have complex social and economic interactions. To investigate the demographic history of Pygmy groups, a population approach was applied to the analysis of 205 complete mitochondrial DNA (mtDNA) sequences from ten central African populations. No sharing of maternal lineages was observed between the two Pygmy groups, with haplogroup L1c being characteristic of the Western group but most of Eastern Pygmy lineages falling into subclades of L0a, L2a, and L5. Demographic inferences based on Bayesian coalescent simulations point to an early split among the maternal ancestors of Pygmies and those of Bantu-speaking farmers (similar to 70,000 years ago [ya]). Evidence for population growth in the ancestors of Bantu-speaking farmers has been observed, starting similar to 65,000 ya, well before the diffusion of Bantu languages. Subsequently, the effective population size of the ancestors of Pygmies remained constant over time and similar to 27,000 ya, coincident with the Last Glacial Maximum, Eastern and Western Pygmies diverged, with evidence of subsequent migration only among the Western group and the Bantu-speaking farmers. Western Pygmies show signs of a recent bottleneck 4,000-650 ya, coincident with the diffusion of Bantu Languages, whereas Eastern Pygmies seem to have experienced a more ancient decrease in population size (20,000-4,000 ya). In conclusion, the results of this first attempt at analyzing complete mtDNA sequences at the population level in sub-Saharan Africa not only support previous findings but also offer new insights into the demographic history of Pygmy populations, shedding new light on the ancient peopling of the African continent.Direccion General de Investigacion, Ministerio de Educacion y Ciencia, Spain [CGL2007-61016]; Direccio General de Recerca, Generalitat de Catalunya [2009SGR1101]info:eu-repo/semantics/publishedVersio

The Genetic Structure and History of Africans and African Americans.

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies

Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model

Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans

Corrigendum to: Cohort profile: Extended Cohort for E-health, Environment and DNA (EXCEED)

This is a correction to: International Journal of Epidemiology, Volume 48, Issue 3, June 2019, Pages 678–679j, https://doi.org/10.1093/ije/dyz07

Visualisation of Integrated Patient-Centric Data as Pathways: Enhancing Electronic Medical Records in Clinical Practice

Routinely collected data in hospital Electronic Medical Records (EMR) is rich and abundant but often not linked or analysed for purposes other than direct patient care. We have created a methodology to integrate patient-centric data from different EMR systems into clinical pathways that represent the history of all patient interactions with the hospital during the course of a disease and beyond. In this paper, the literature in the area of data visualisation in healthcare is reviewed and a method for visualising the journeys that patients take through care is discussed. Examples of the hidden knowledge that could be discovered using this approach are explored and the main application areas of visualisation tools are identified. This paper also highlights the challenges of collecting and analysing such data and making the visualisations extensively used in the medical domain. This paper starts by presenting the state-of-the-art in visualisation of clinical and other health related data. Then, it describes an example clinical problem and discusses the visualisation tools and techniques created for the utilisation of these data by clinicians and researchers. Finally, we look at the open problems in this area of research and discuss future challenges