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Human genomic diversity in Europe: a summary of recent research and prospects for the future
Abstract
Gene frequencies in Europe are intermediate with respect to those of other continents. A phylogenetic tree reconstructed from 95 gene frequencies tested on 26 European samples shows some deviant populations (Lapps, Sardinians, Greeks, Yugoslavs, Basques, Icelanders and Finns) and other weakly structured populations. This behavior may have a simple interpretation: Europeans have not evolved according to a tree of descent probably because of the major role played by migrations in prehistorical and historical times. The leading component of the European genetic landscape is a gradient that originates in the Middle East and is directed to the northwest. According to the hypothesis by Ammerman and Cavalli-Sforza this gradient was generated by a migration of Neolithic farmers from Anatolia followed by continuous, partial admixture of the expanding farmers with local hunter-gatherers. Other leading components of the gene frequencies in Europe show correlations with possible movements of Uralic-speaking people and pastoral nomads from a region north of the Caucasus and Black Sea, which according to Gimbutas is the area of origin of Indo-European speakers. This analysis is based on classical pre-DNA genetic markers. The prospect of future research using DNA polymorphisms is discussed in the context of the Human Genome Project.
... Due to its geographic isolation in the Mediterranean sea, the biological history of Sardinia has been the subject of extensive anthropological and population-genetics investigation. Several studies based on autosomal markers [1][2][3][4] , mitochondrial DNA (mtDNA) [5][6][7][8][9] and Y-chromosome polymorphisms [10][11][12][13] showed that the Sardinian population is one of the main European genetic outliers [14][15][16][17] and reported unusually high levels of internal diversity 18,19 . Most of these studies compared variation in Sardinia and in other European populations, but there is still uncertainty about past population dynamics and demographic processes within the island, as well as about the exact nature and the extent of the genetic exchanges that occurred over millennia, actually determining the existing Sardinian genetic structure. ...
... The second, which we called "discontinuity", assumed a complete replacement of ancient Mesolithic Sardinia by Neolithic people from Continental Europe. Under the third model the current inhabitants of Sardinia are a genetic mixture of local Mesolithic individuals and Neolithic individuals from the Sample ID 14 We determined the accuracy of our model choice inference by calculating the true and the false positive rates using 1,000 random simulations from each model as pseudo-observed datasets; the results are shown in Supplementary Table S9. The true positives rate was high for all the models, ranging from 0.64 to 0.89. ...
Little is known about the genetic prehistory of Sardinia because of the scarcity of pre-Neolithic human remains. From a genetic perspective, modern Sardinians are known as genetic outliers in Europe, showing unusually high levels of internal diversity and a close relationship to early European Neolithic farmers. However, how far this peculiar genetic structure extends and how it originated was to date impossible to test. Here we present the first and oldest complete mitochondrial sequences from Sardinia, dated back to 10,000 yBP. These two individuals, while confirming a Mesolithic occupation of the island, belong to rare mtDNA lineages, which have never been found before in Mesolithic samples and that are currently present at low frequencies not only in Sardinia, but in the whole Europe. Preliminary Approximate Bayesian Computations, restricted by biased reference samples for Mesolithic Sardinia (the two typed samples) and Neolithic Europe (limited to central and north European sequences), suggest that the first inhabitants of the island have had a small or negligible contribution to the present-day Sardinian population, which mainly derives its genetic diversity from continental migration into the island by Neolithic times.
... No prevalence data has been published for Denmark. Considering the genetic outliers of Europe to which Icelanders and Finns belong (Cavalli-Sforza & Piazza 1993), HD prevalence data exists for Greeks with an ascertained minimum prevalence of 2.5/100,000 and an extrapolated prevalence estimate of 5.4/100,000 based on information of relatives who have not been tested. Clusters of HD families were found in different parts of the country which was not surprising, considering the relative genetic isolation of the Greek population and the characteristics of the cluster areas. ...
... This overrepresentation is a consequence of founder effects, bottlenecks and random genetic drift in a small and isolated population. (Norio 2003a-b;Liu and Fu 2015) Finns have been identified as one of the genetic outlier populations of Europe along with Lapps, Sardinians, Greeks, Yugoslavs, Basques and Icelanders, but still being genetically the closest of these outliers to other European populations (Cavalli-Sforza & Piazza 1993). A recent study concluded that Finns should be placed further apart from other European populations, including Greeks and Yugoslavs (Lao et al. 2008). ...
Huntington's disease (HD) is a lethal, dominantly inherited neurodegenerative disorder reported to be unusually rare in Finland. The overall HD prevalence and the proportion of late-onset cases (LOHD) are increasing in many populations. The characteristics of LOHD are nevertheless poorly understood. Information on neurological comorbidity in patients with HD is also scarce. These retrospective studies analyzed a national Finnish HD cohort in the time frame 1987-2010 by searching national registries and archives. Data was extracted from medical records. Population genotypes were obtained from the 1000 Genomes project.
The prevalence of HD in Finland was found to be 2.12/100,000, or over four times more common than reported previously. Nonetheless, HD is more uncommon than in other Western European countries. The national cohort of 207 patients included 52 (25%) patients with LOHD; they had poorer motor status at the time of diagnosis than patients with mid-age onset, possibly because of the diagnostic delay. No other differences were detected between these groups. Interestingly, only one individual (0.5% of all HD patients in Finland) with juvenile-onset HD was identified.
The length of the affected CAG repeat or its intergenerational stability did not differ from those reported in other populations. However, the high risk chromosome 4 haplogroup A was relatively uncommon in the Finnish general population (39.2%), possibly partly explaining the relative rarity of HD in Finland.
Patients with adult-onset HD had epilepsy and strokes as often as reported in the general population. HD patients were, however, at an increased risk of suffering subdural haematomas.
... The genetic diversity observed in our sample is broadly comparable to that seen in European populations, which exhibit variation along both East-West and North-South axes (28,29). The investigation of genetic risks for common disorders, prevalent across all populations, underscores the necessity of including large, continental samples. ...
Genome-wide association studies across diverse populations may help validate and confirm genetic contributions to risk of disease. We estimated the extent of population stratification as well as the predictive accuracy of polygenic scores (PGS) derived from European samples to a data set from India. We analysed 2685 samples from two data sets, a population neurodevelopmental study (cVEDA) and a hospital-based sample of bipolar affective disorder (BD) and obsessive-compulsive disorder (OCD). Genotyping was conducted using Illumina's Global Screening Array.
Population structure was examined with principal component analysis (PCA), uniform manifold approximation and projection (UMAP), support vector machine (SVM) ancestry predictions, and admixture analysis. PGS were calculated from the largest available European discovery GWAS summary statistics for BD, OCD, and externalizing traits using two Bayesian methods that incorporate local linkage disequilibrium structures (PGS-CS-auto) and functional genomic annotations (SBayesRC). Our analyses reveal global and continental PCA overlap with other South Asian populations. Admixture analysis revealed a north-south genetic axis within India (FST 1.6%). The UMAP partially reconstructed the contours of the Indian subcontinent.
The Bayesian PGS analyses indicates moderate-to-high predictive power for BD. This was despite the cross-ancestry bias of the discovery GWAS dataset, with the currently available data. However, accuracy for OCD and externalizing traits was much lower. The predictive accuracy was perhaps influenced by the sample size of the discovery GWAS and phenotypic heterogeneity across the syndromes and traits studied. Our study results highlight the accuracy and generalizability of newer PGS models across ancestries. Further research, across diverse populations, would help understand causal mechanisms that contribute to psychiatric syndromes and traits.
... Finland is a relatively sparsely inhabited country, with a total population of slightly over 5.5 million (Figure 1), and it is within the genetic margins of Europe [1][2][3]. Its genetic history is marked by bottlenecks, founder effects and drift [4][5][6]. ...
Finland is a relatively small genetic isolate with a genetically non-homogenous population. Available Finnish data on neuroepidemiology of adult-onset disorders are limited, and this paper describes the conclusions that can be drawn and their implications. Apparently, Finnish people have a (relatively) high risk of developing Unverricht-Lundborg disease (EPM1), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Spinal muscular atrophy, Jokela type (SMAJ) and adult-onset dystonia. On the other hand, some disorders, such as Friedreich’s ataxia (FRDA) and Wilson’s disease (WD), are almost absent or completely absent in the population. Valid and timely data concerning even many common disorders, such as stroke, migraine, neuropathy, Alzheimer’s disease and Parkinson’s disease, are unavailable, and there are virtually no data on many less-common neurological disorders, such as neurosarcoidosis or autoimmune encephalitides. There also appear to be marked regional differences in the incidence and prevalence of many diseases, suggesting that non-granular nationwide data may be misleading in many cases. Concentrated efforts to advance neuroepidemiological research in the country would be of clinical, administrative and scientific benefit, but currently, all progress is blocked by administrative and financial obstacles.
... Like many other genetic polymorphisms, the ε4 allele's prevalence in Europeans exhibits a remarkably interesting gradient that is oriented from south to north. The proportion of ε4 carriers increases from 10%-15% in southern Europe to 40%-50% in the northern part of the continent [46]. The frequency of the ε4 allele in our population of Romania does not respect the geographical pattern of ApoE alleles' frequencies. ...
Background
Apolipoprotein E (ApoE) is a ubiquitous protein involved in maintaining cholesterol homeostasis and lipoprotein clearance from circulation. It is coded by three alleles (ε2, ε3, ε4) with six genotypes (ε3/ε3, ε3/ε4, ε2/ε3, ε4/ε4, ε2/ε4, and ε2/ε2). Several studies have shown a relationship between ApoE-specific isoforms and different diseases. There are few data about the prevalence of ApoE polymorphism in the Romanian population. We aimed to assess the prevalence of Apolipoprotein E alleles in a healthy population from Romania and compare it with the data found in other countries of Europe.
Methods
ApoE genotype was examined in 187 unrelated healthy volunteers (131 males and 56 females) from the region of southwest Romania (mean age 48.04 ± 8.35 years). Analysis of ApoE genotype variants was done using the PCR method with allele-specific oligonucleotide primers.
Results
The frequency of heterozygote genotypes ε2/ε3, ε2/ε4, and ε3/ε4 was 4.8%, 1.6%, and 24.73%, respectively, while the frequency of homozygote genotypes ε2/ε2, ε3/ε3, ε4/ε4 was 0.5%, 66.12%, and 2.1%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 6.9%, 96.25%, and 28.49%, respectively. East European countries have the lowest mean frequency of the ε4 allele (9.96%), and the highest frequency of the ε4 allele (23.38%) is in the Nordic Countries.
Conclusions
The ε4 allele prevalence in this Romanian population is higher in comparison with other European countries, similar to Nordic countries of Europe.
... Sardinia is the second largest Mediterranean island characterized by a relative socio-cultural isolation over the centuries (4,5). This probably accounts for some peculiarities of ALS in Sardinia, including the high frequency of family history and of patients carrying TARDBP and C9orf72 mutations (6,7). ...
Objective: This study assessed amyotrophic lateral sclerosis (ALS) incidence in Sardinia, Italy, and the combined contribution of age and gender to disease risk. We also checked disease incidence for spatial-temporal variability. Methods: ALS patients from all neurological centers of the study area who had onset during 2010-2019 and fulfilled El Escorial revised diagnostic criteria were included. Incidence was calculated for the overall study area and each province separately. Additive interaction between age and sex on ALS incidence was assessed. Results: The average crude annual incidence rate was 3.6/100,000 person-years (95% CI, 3.2-4.1), 3.1/100,000 person-years (95% CI, 2.7-3.5) when age-adjusted. Incidence was greater among people aged ≥65 years and men, with the two variables undergoing significant additive interaction. Incidence increased yearly over the study period, with annual incidence correlating with the increasing yearly frequency of people aged ≥65 years, but not with the proportion of incident cases carrying genetic mutations. Stratifying by province, the rates from Oristano and South Sardinia were higher than the rate from Cagliari. ALS patients from areas at different risk were comparable for frequency of clinical/genetic features. Conclusion: ALS incidence in Sardinia was in the upper part of the European range of variability. We also provided new information about age and sex as risk factors for ALS, showing male sex as a modifier of the effect of aging on ALS incidence. Spatial-temporal variations in ALS incidence correlated to changes in the proportion of the aging population rather than to the distribution of genetic factors.
... From the archaeological standpoint, although it is apparent a significant population expansion coinciding with the Early Neolithic period occurred (about 7,700 years ago), there is also evidence of a stable Mesolithic occupation, raising the question of whether the neolithisation was carried out by people who replaced the autochthonous residents, or if there was an appreciable genetic contribution by the pre-Neolithic population, and farming was at least partially due to cultural acquisition. In addition, Sardinia has also been defined as a genetically isolated population on the basis of classical autosomal markers, uniparental markers, and elevated linkage disequilibrium (Barbujani and Sokal 1990;Cavalli-Sforza and Piazza 1993;Zavattari et al. 2000;Cal o et al. 2008;Piras et al. 2012), and it would be rather surprising if such an elevated genetic drift, able to move Sardinians to an outlier position in the European genetic variability, would have maintained the original Neolithic genetic frequencies unaltered for over seven millennia. ...
Context
For many years the Sardinian population has been the object of numerous studies because of its unique genetic structure. Despite the extreme abundance of papers, various aspects of the peopling and genetic structure of Sardinia still remain uncertain and sometimes controversial.
Objective
We reviewed what has emerged from different studies, focussing on some still open questions, such as the origin of Sardinians, their relationship with the Corsican population, and the intra-regional genetic heterogeneity.
Methods
The various issues have been addressed through the analysis of classical markers, molecular markers and, finally, genomic data through next generation sequencing.
Results and conclusions
Although the most ancient human remains date back to the end of the Palaeolithic, Mesolithic populations brought founding lineages that left evident traces in the modern population. Then, with the Neolithic, the island underwent an important demographic expansion. Subsequently, isolation and genetic drift contributed to maintain a significant genetic heterogeneity, but preserving the overall homogeneity on a regional scale. At the same time, isolation and genetic drift contributed to differentiate Sardinia from Corsica, which saw an important gene flow from the mainland. However, the isolation did not prevent gene flow from the neighbouring populations whose contribution are still recognisable in the genome of Sardinians.
... Sardinians, albeit clearly Europeans, represent the main outlying gene pool in the European genetic landscape [1][2][3][4][5]. To understand the origin and the evolutionary forces at the basis of their differentiation, Sardinians have been the subject of numerous genetic, linguistic and anthropological analyses. ...
Many anthropological, linguistic, genetic and genomic analyses have been carried out to evaluate the potential impact that evolutionary forces had in shaping the present-day Sardinian gene pool, the main outlier in the genetic landscape of Europe. However, due to the homogenizing effect of internal movements, which have intensified over the past fifty years, only partial information has been obtained about the main demographic events. To overcome this limitation, we analyzed the male-specific region of the Y chromosome in three population samples obtained by reallocating a large number of Sardinian subjects to the place of origin of their monophyletic surnames, which are paternally transmitted through generations in most of the populations, much like the Y chromosome. Three Y-chromosome founding lineages, G2-L91, I2-M26 and R1b-V88, were identified as strongly contributing to the definition of the outlying position of Sardinians in the European genetic context and marking a significant differentiation within the island. The present distribution of these lineages does not always mirror that detected in ancient DNAs. Our results show that the analysis of the Y-chromosome gene pool coupled with a sampling method based on the origin of the family name, is an efficient approach to unravelling past heterogeneity, often hidden by recent movements, in the gene pool of modern populations. Furthermore, the reconstruction and comparison of past genetic isolates represent a starting point to better assess the genetic information deriving from the increasing number of available ancient DNA samples.
... One key characteristic of Sardinia is its differentiation from mainland populations, as evidenced by a distinctive cultural, linguistic, and archaeological legacy 10,11 . Early genetic studies made clear that Sardinia has also been a genetically isolated population on the basis of classical autosomal markers, uniparental markers, and elevated linkage disequilibrium (LD) [12][13][14][15][16][17] . Partly on this basis, Sardinia was included in the Human Genome Diversity Project (HGDP; see Cann 18 ), which has been used as a reference sample in many studies, including recent ancient DNA (aDNA) studies of Europe [19][20][21][22][23] . ...
The population of the Mediterranean island of Sardinia has made important contributions to genome-wide association studies of complex disease traits and, based on ancient DNA studies of mainland Europe, Sardinia is hypothesized to be a unique refuge for early Neolithic ancestry. To provide new insights on the genetic history of this flagship population, we analyzed 3,514 whole-genome sequenced individuals from Sardinia. Sardinian samples show elevated levels of shared ancestry with Basque individuals, especially samples from the more historically isolated regions of Sardinia. Our analysis also uniquely illuminates how levels of genetic similarity with mainland ancient DNA samples varies subtly across the island. Together, our results indicate that within-island substructure and sex-biased processes have substantially impacted the genetic history of Sardinia. These results give new insight into the demography of ancestral Sardinians and help further the understanding of sharing of disease risk alleles between Sardinia and mainland populations.
... The number of copies correlates with reliance on a starch-rich diet (probably initially due to exploitation of roots and tubers, and later due to agriculture), with up to nine copies found in some contemporary populations. Such populationlevel differences in allele frequencies can be used to test hypotheses about early human movements, such as the origins and early movements of Indo-European language speakers into Europe and India, complementing historical linguistic data (Bouckaert et al., 2012;Cavalli-Sforza & Piazza, 1993;Gray & Atkinson, 2003). But again, none of these differences are likely to provide clues to genes involved specifically in language, because of the homogeneity of the human language faculty. ...
The study of language evolution, and human cognitive evolution more generally, has often been ridiculed as unscientific, but in fact it differs little from many other disciplines that investigate past events, such as geology or cosmology. Well-crafted models of language evolution make numerous testable hypotheses, and if the principles of strong inference (simultaneous testing of multiple plausible hypotheses) are adopted, there is an increasing amount of relevant data allowing empirical evaluation of such models. The articles in this special issue provide a concise overview of current models of language evolution, emphasizing the testable predictions that they make, along with overviews of the many sources of data available to test them (emphasizing comparative, neural, and genetic data). The key challenge facing the study of language evolution is not a lack of data, but rather a weak commitment to hypothesis-testing approaches and strong inference, exacerbated by the broad and highly interdisciplinary nature of the relevant data. This introduction offers an overview of the field, and a summary of what needed to evolve to provide our species with language-ready brains. It then briefly discusses different contemporary models of language evolution, followed by an overview of different sources of data to test these models. I conclude with my own multistage model of how different components of language could have evolved.
... It has been shown that average estimates of G ST obtained from a representative set of polymorphic markers can reflect a selectively neutral process in the formation of a gene pool (Bowcock et al., 1991;Cavalli-Sforza and Piazza, 1993;Poloni et al., 1995). This method has been used for the analysis of cranial nonmetric trait diversity in world populations, and a strong similarity between genetic and phenetic estimates was found (Movsesian, 2005). ...
Objectives:
Within the fields of archaeology and anthropology, there is a long history of disputes concerning the origin of the northern Black Sea Scythians. One of the main points of contention is whether the Scythian gene pool was derived from the preceding local Bronze Age population or whether their population history can be connected to invaders from Central Asia. To test these hypotheses, we investigated Late Scythian populations from the northern Black Sea region and compared them to Bronze Age groups from Eastern Europe and Central Asia.
Materials and methods:
We studied a cranial series of five Late Scythian populations from the northern Black Sea region (N = 323), as well as local Bronze Age groups (N = 109), Central Asian Bronze Age groups (N = 79), and Sarmatians (N = 110). Biological diversity was analyzed by the mean measure of divergence (MMD).
Results:
The Late Scythian population considered in this study proved to be genetically homogeneous, although some connections with the Sarmatians were found. We also revealed similarities between the Scythian groups and the local Bronze Age population of the Srubnaya culture, as well as, to a lesser extent, a group representative of the Central Asian Bronze Age Okunevo culture.
Discussion:
The similarities between Late Scythians and various Sarmatian groups could be the result of genetic contacts between the groups, as well as shared genetic origins. The gene pool of the Scythian population likely comprises both local and Central Asian genetic components, though the exact origins and proportion of the eastern component currently remains unknown.
... Today, the term "predictive medicine" is replaced by one that is more precise: "personalized medicine" and "precision medicine" enabled by the introduction and availability of high-throughput genomics technologies ( Hizel et al., 2009;Aydin Son et al., 2013). As a consequence of genetic diversity and the existence of our genes in different forms in different environments with different lifestyles, the genetic basis of individual approach is resumed as "we are all different," which reflects the presence of genetic diversity (Cavalli Sforza and Piazza, 1993;Cavalli-Sforza, 1997). Behind this expression, there is a scientific phenomenon called polymorphism. ...
With the availability of high-throughput genomics technologies and the completion of the Human Genome Project in 2003, we are now in the “postgenomics era.” The concept of precision medicine evolved over time and was popularized only recently. It became a hot topic in the medical community as well as in public sphere due to president Obama's announcement of the “Precision Medicine Initiative” at the beginning of 2015. In principle, the term “precision medicine” referring to multiple omics profiles, which include genomics, pharmacogenomics, proteomics, metabolomics, transcriptomics, epigenomics, and metagenomics, takes into account family history and lifestyles to make more tailored diagnostic and therapeutic strategies to a particular patient with different monogenic and multifactorial polygenic complex diseases, such as diabetes. The term “personalized medicine” is wider, more inclusive of subjects' environment, exposure, and socioeconomic status. However, besides technical issues, as a cornerstone of individual approach, precision medicine can fulfill its promise and build its sustainable existence by addressing and asking precision questions regarding structural deficiencies in health care system for the most vulnerable patients and pathologies including neglected diseases and global epidemic of complex noncommunicable diseases, such as diabetes in the society of not only high-income but also in low- and middle-income countries.
... The picture emerging here, then, is one of acquisition of Neolithic technology by hunter-gatherers and commercialisation of hunter-gatherer communities during some 3000 years before the final adoption of farming (Tab. 1, Fig. 5 A wide range of genetic studies, relating to the agricultural transition in Europe and the origins of the Neolithic, has been carried out to date (i.e. Ammerman and Cavalli-Sforza 1984; Cavalli-Sforza 1991; Cavalli-Sforza and Piazza 1993; Cavalli-Sforza et al. 1994; Cavalli-Sforza and Cavalli-Sforza 1995; Richards et al. 1996; Calafell and Betranpetit 1993; Barbujani and Sokal 1990; Sokal et al. 1989; 1991; Torronni et al. 1998; Renfrew and Boyle 2000; etc.). These studies include human DNA, as well as the DNA of domestic plants and animals (i.e. ...
The origin of Neolithic societies and the agricultural transition have been a subject of concentrated attention and a subject of debate and controversy among archaeologist, geneticists and linguists. In my contribution I review and evaluate different archaeological interpretations of the transition to farming. I will also discuss the archaeogenetic evidence and its integration with archaeological data.
... Genetic analysis has proven that the historical, geographical and cultural isolation of Sardinia from European and African populations has maintained the genome background of Sardinians stable for centuries [8,9]. The identification of Sardinia as an area with an elevated T1DM incidence renders the island an ideal epidemiological environment to design studies aimed at identifying individuals at risk of developing the disease [10]. ...
... Such variation seems unlikely to be explained by genetic differences, since Europeans (except for some outlying populations) are more homogeneous compared with the indigenous populations of other continents. 13 Although the independence of primary and secondary sources of ascertainment cannot easily be verified our assessment of completeness is more thorough than in most previous studies of international variations in incidence, and underascertainment is unlikely to be a major factor in explaining the incidence variation described here. ...
Background To study the epidemiology of childhood-onset type 1 insulin-dependent diabetes in Europe, the EURODIAB collaborative group established in 1988 prospective geographically-defined registers of new cases diagnosed under 15 years of age. This report is based on 16 362 cases registered during the period 1989-94 by 44 centres representing most European countries and Israel and covering a population of about 28 million children. Methods Multiple sources of ascertainment were used in most centres to Validate the completeness of registration by the capture-recapture method. Trends in incidence during the period were analysed by Poisson regression, the data from centres within each country being pooled. Findings The standardised average annual incidence rate during the period 1989-94 ranged from 3.2 cases per 100 000 per year in the Former Yugoslav Republic of Macedonia to 40.2 cases per 100 000 per year in two regions of Finland. By pooling over all centres, the annual rate of increase in incidence was 3.4% (95% CI 2.5-4.4%), but in some central European countries it was more rapid than this. Pooled over centres and sexes, the rates of increase were 6.3% (4.1-8.5%) for children aged 0-4 years, 3.1% (1.5-4.8%) for 5-9 years, and 2.4% (1.0-3.8%) for 10-14 years. Interpretation The results confirm a very wide range of incidence rates within Europe and show that the increase in incidence during the period varied from country to country. The rapid rate of increase in children aged under 5 years is of particular concern.
... Through genetical markers some populations that clearly deviate from the rest of Europe has been identified. Those are the Sardinians, Greeks, Basques, Finns and particularly the Sami (Cavalli-Sforza & Piazza 1993;Tambets et al. 2004;Beckman et al. 2001;Fan et al. 1993). Even if the genetical composition of the Sami regarding certain markers resembles some Asiatic-Mongoloid populations, the Sami is believed to have their genetical roots in a small, distinctive European subpopulation. ...
... Найдена лишь слабая взаи мосвязь с климатическими особенностями, что поз волило предположить, что климатические особенно сти не являются объяснением имеющегося широтного градиента. Авторы предлагают альтерна тивное объяснение, что в основе широтного градиен та могут лежать генетические различия популяций, отражающие историческую миграцию населения древнего мира со Среднего Востока через Восточную Европу в северо-западном направлении и частичного смешения с местными племенами [38]. ...
В последние десятилетия в различных регионах мира проводятся углубленные эпидемиологические исследования СД (СД) типа 1, которые позволят уточнить вопросы этиопатогенеза этого заболевания. Международная группа (IDF) по изучению эпидемиологии СД типа 1 включает 32 страны мира. Наиболее полно распространенность и заболеваемость СД типа 1 изучена в следующих регионах: африканском регионе (AFR); восточно-средиземноморском регионе и странах Ближнего Востока (ЕММЕ); европейском регионе (EUR); Северной Америке (NA); Южной и Центральной Африке (SACA); странах Юго-Восточной Азии (SEA); западном тихоокеанском регионе (WP).
... The low prevalence of HD in Finland has been attributed to the geographic, cultural and linguistic isolation of the Finnish population. Among Caucasian populations a similar low prevalence has been reported among the Greeks and Icelanders [19], [20] that, together with Finns, belong to the genetic outliers in Europe [21]. The genetic structure of outlying populations may determine their susceptibility to certain genetic diseases. ...
To estimate the prevalence of Huntington's disease (HD) in Finland.Methods
Persons diagnosed with HD from 1987 to 2010 were identified in the national registers and hospital records of the identified patients, and death certificates of the deceased subjects were obtained. Results of genetic analyses were obtained from the two national laboratories.ResultsFollowing the discovery of the Huntingtin gene (HTT), the rate of new diagnoses of HD has increased in Finland. We ascertained 207 patients with HD, 114 of whom were alive on 31 December, 2010 suggesting a minimum estimate of point prevalence of 2.12/100,000. The age at the time of diagnosis was 52.6 ± 12.1 years (mean ± standard deviation) and the duration of the disease was 8.5 ± 4.4 years among deceased patients. The length of the CAG repeats in the affected allele was 43.3 ± 3.5 repeats and the length was inversely correlated with the age at diagnosis (β = −0.73, p < 0.001). The number of diagnoses varied regionally, whereas the repeat length did not. The frequency of the high risk HTT haplogroup A was 39% in Finnish chromosomes abstracted from the 1000 Genomes database compared to 53% in other European samples (p = 0.024).Conclusions
The annual rate of HD diagnoses and the age at diagnosis have increased. The prevalence of HD in the Finnish population is lower than that of other Caucasian populations, partly explained by the low frequency of HTT haplogroup A among the Finns.
http://www.prd-journal.com/article/S1353-8020%2814%2900410-6/fulltext
... These studies of Sardinian migrants show beyond any doubt that the much higher incidence of Type 1 diabetes they have, compared to other neighbouring populations, is an exclusive consequence of their genetic features. In fact, Sardinians are a homogeneous population that originated from an early split in the Caucasian cluster and are genetically distinct from other European populations, including Italians [60]. This is the basis of the differences in frequencies of some HLA haplotypes among Sardinians and other Caucasians, as shown in Table 2, and hence of the peculiar proneness of Sardinians to Type 1 diabetes. ...
In Mediterranean countries, the incidence (per 100 000 per year) of Type 1 diabetes in children aged under 15 years shows wide variation from country to country, ranging from 2.45 in Macedonia to 34.4 in Sardinia. By interacting with environmental factors such as diet, toxins or viral infections, the HLA plus non-HLA genes of susceptibility or resistance to Type 1 diabetes so far identified are the strongest determinants of the disease as far as incidence, age at onset and sex ratio are concerned. The distribution of these genes in the Mediterranean region is still not completely known.Sardinians are the most suitable population for studying such phenomena for three main reasons: their genetic features have been repeatedly analysed in depth; their incidence rate of Type 1 diabetes is by far the highest in the Mediterranean area; and considerable colonies of Sardinian emigrants settled in neighbouring low-incidence Italian regions. Studies on Spaniards and Jews have also contributed to a better understanding of the respective roles of genetic and environmental factors. From a body of research on the Mediterranean populations, it can be concluded that great genetic heterogeneity accounts for the wide variation in incidence of Type 1 diabetes, while rather ubiquitous environmental factors trigger the disease in genetically predisposed individuals. Copyright © 1999 John Wiley & Sons, Ltd.
... . A survey reported F ST estimates with a median of 0.008 and a 90th percentile of 0.028 among Europeans; the corresponding values were 0.027 and 0.14, respectively, among Africans, and 0.043 and 0.12, respectively, among Asian (Cavalli-Sforza and Piazza, 1993). The values for Wright's F ST were assumed to be 0.005, 0.01, and 0.05. ...
Motivation:
Individuals in each family are genetically more homogeneous than unrelated individuals, and family-based designs are often recommended for the analysis of rare variants. However, despite the importance of family-based samples analysis, few statistical methods for rare variant association analysis are available.
Results:
In this report, we propose a FAmily-based Rare Variant Association Test (FARVAT). FARVAT is based on the quasi-likelihood of whole families, and is statistically and computationally efficient for the extended families. FARVAT assumed that families were ascertained with the disease status of family members, and incorporation of the estimated genetic relationship matrix to the proposed method provided robustness under the presence of the population substructure. Depending on the choice of working matrix, our method could be a burden test or a variance component test, and could be extended to the SKAT-O-type statistic. FARVAT was implemented in C++, and application of the proposed method to schizophrenia data and simulated data for GAW17 illustrated its practical importance.
Availability:
The software calculates various statistics for the analysis of related samples, and it is freely downloadable from http://healthstats.snu.ac.kr/software/farvat.
Contact:
won1@snu.ac.kr or tspark@stats.snu.ac.kr
Supplementary information:
supplementary data are available at Bioinformatics online.
... Finally, Spanish sample size was relatively small and other genetic variants were previously investigated in this sample ( Arias et al., 2003;Arias et al., 2006;Arias et al., 2009;Mitjans et al., 2012). A point of strength of the present study is the selection of the sample in the north-east of Spain, a region characterized by a substantial genetic homogeneity (Cavalli-Sforza and Piazza, 1993). ...
Background
Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MDD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISC1), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DAOA) were suggested since their regulator role in neurodevelopment, neuroplasticity and neurotransmission, and previous evidence of cross-involvement in major psychiatric diseases.
Methods
The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case-control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR⁎D genome-wide dataset (n=1892) for replication.
Results
Evidence of association among rs3738401 (DISC1), rs1615409 and rs766288 (TSNAX) and MDD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISC1 rs821616 and DAOA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR⁎D a cluster of SNPs from 20 to 40 Kbp from DISC1 findings in the original sample was associated with citalopram response, as well as rs778330 (12,325 bp from rs778294).
Limitations
Relatively small size of the original sample and focus on only three candidate genes.
Conclusions
The present study supported a role of DISC1-TSNAX variants in MDD susceptibility. On the other hand, genetic regions around DAOA rs778294 and DISC1 rs6675281-rs1000731 may influence citalopram efficacy.
... Sardinians have long been recognized as forming a distinct outlier within contemporary European genetic diversity (e.g. [37]), often interpreted as a consequence of genetic isolation and/or founder effects in the demographic history of the island. It is thought that permanent settlement of the island was established by around 10,000 YBP, and recent results from both genetic and cranial morphological data suggest population continuity since the Neolithic [38][39][40]. ...
Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.
... Sardinians have long been recognized as forming a distinct outlier within contemporary European genetic diversity (e.g. [37]), often interpreted as a consequence of genetic isolation and/or founder effects in the demographic history of the island. It is thought that permanent settlement of the island was established by around 10,000 YBP, and recent results from both genetic and cranial morphological data suggest population continuity since the Neolithic [38][39][40]. ...
Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.
... [5][6][7] Cavalli-Sforza et al proposed a phylogenetic tree dividing the world population into nine subpopulations: New Guinean and Australian, Pacific Islander, Southeast Asian, Northeast Asian, Arctic Northeast Asian, Amerind, European, North African and West Asian, and African. [8][9][10] This subdivision is based on genetic polymorphism studies in various populations grouped by continental sub-areas. F ST statistics compute genetic distance between populations by measuring the portion of total genetic variation attributed to differences between them. ...
3D analysis of facial morphology has delineated facial phenotypes in many medical conditions and detected fine grained differences between typical and atypical patients to inform genotype-phenotype studies. Next-generation sequencing techniques have enabled extremely detailed genotype-phenotype correlative analysis. Such comparisons typically employ control groups matched for age, sex and ethnicity and the distinction between ethnic categories in genotype-phenotype studies has been widely debated. The phylogenetic tree based on genetic polymorphism studies divides the world population into nine subpopulations. Here we show statistically significant face shape differences between two European Caucasian populations of close phylogenetic and geographic proximity from the UK and The Netherlands. The average face shape differences between the Dutch and UK cohorts were visualised in dynamic morphs and signature heat maps, and quantified for their statistical significance using both conventional anthropometry and state of the art dense surface modelling techniques. Our results demonstrate significant differences between Dutch and UK face shape. Other studies have shown that genetic variants influence normal facial variation. Thus, face shape difference between populations could reflect underlying genetic difference. This should be taken into account in genotype-phenotype studies and we recommend that in those studies reference groups be established in the same population as the individuals who form the subject of the study.European Journal of Human Genetics advance online publication, 8 January 2014; doi:10.1038/ejhg.2013.289.
... It has been shown that average estimates of G ST obtained from a representative set of polymorphic markers can reflect a selectively neutral process in the formation of a gene pool (Bowcock et al., 1991;Cavalli-Sforza and Piazza, 1993;Poloni et al., 1995). This method has been used for the analysis of cranial nonmetric trait diversity in world populations, and a strong similarity between genetic and phenetic estimates was found (Movsesian, 2005). ...
The population history of the East Slavs is complicated. There are still many unanswered questions relating to the origins and formation of the East Slavic gene pool. The aims of the current study were as follows: (1) to assess the degree of biological affinity in medieval East Slavic tribes and to test the hypothesis that East Slavic peoples have a common origin; (2) to show their genetic connections to the autochthonous populations of the northern part of Eastern Europe (Baltic and Finno-Ugric tribes); and (3) to identify a genetic continuity between the bearers of Chernyakhov culture and medieval Eastern Slavs. In this study, nonmetric cranial trait data for medieval East Slavic tribes and comparative samples from unrelated groups were examined. Analyzes of phenotypic differentiation were based on Nei's standard genetic distance and hierarchical GST statistics. The results obtained suggest that the genetic affinity of the East Slavic tribes is due not only to inter-tribal gene flow, but is, more importantly, a result of their common population history. Evidence of gene flow from the Baltic and Finno-Ugric groups was showed in the gene pool of Eastern Slavs, as was genetic continuity between medieval East Slavic tribes and the populations of the preceding Chernyakhov culture. These findings support a "generalizing" hypothesis of East Slavic origin, in which a Slavic community was formed in some particular ancestral area, and subsequently spread throughout Eastern Europe. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc.
... Further, only limited data for assessing FST values are yet available on the relevant demographic scales. Published estimates of FST at forensic loci are usually small (16,17), typically much smaller than the values for traditional loci (18), although recent analyses of forensic data using a different method of estimation (D.J.B. and R. A. Nichols, unpublished work) suggest appreciable values of FST which cannot reasonably be ignored in forensic settings. ...
The controversy over the interpretation of DNA profile evidence in forensic identification can be attributed in part to confusion over the mode(s) of statistical inference appropriate to this setting. Although there has been substantial discussion in the literature of, for example, the role of population genetics issues, few authors have made explicit the inferential framework which underpins their arguments. This lack of clarity has led both to unnecessary debates over ill-posed or inappropriate questions and to the neglect of some issues which can have important consequences. We argue that the mode of statistical inference which seems to underlie the arguments of some authors, based on a hypothesis testing framework, is not appropriate for forensic identification. We propose instead a logically coherent framework in which, for example, the roles both of the population genetics issues and of the nonscientific evidence in a case are incorporated. Our analysis highlights several widely held misconceptions in the DNA profiling debate. For example, the profile frequency is not directly relevant to forensic inference. Further, very small match probabilities may in some settings be consistent with acquittal. Although DNA evidence is typically very strong, our analysis of the coherent approach highlights situations which can arise in practice where alternative methods for assessing DNA evidence may be misleading.
... In case of rs3740487 and rs3824783, no subpopulations were with alternative alleles " A " and " G " , respectively [Figures 4,5,8,9]. These allelic frequency variations may be due to within and between population stratification, ancestral geographical migration, marriage practices, reproductive expansions and bottlenecks, and stochastic variation. [9,10] The extent of genetic diversity among different Indian population is well observed in the entire globe with the exception of African population. [11] However, the Indian(d). (Freq ≥0.90 & <1.00), P15, P48 (2 population) (e). (Freq=1.00), P19 (1 ...
Evolution paved the way for many social constructs. Race is the social construct of evolution. Europeans are the least genetically diverse race thus resulting in their toxic individualism and white privilege. Europeans were the last race to settle. The Europeans are part of the Causcioids and diverged out of the Mongoloids. The Mongoloids had previously diverged out of the Negroids. Thus, emerged the two main political divisions of the Europeans, the conservatives and the liberals. The conservatives care less about nature. The liberals care more about nature. Such is the result of being removed from genetic diversity by mutations due to cold weather. The current threat of climate change is posed to global genetic diversity due to global warming. Europeans originate from decreased genetic diversity due to cooling. Thus, Europeans may instinctively know of the benefits of cooler weather towards them, so by the Lindy effect they created the Democratic party of the United States of America. The Democratic Party is the oldest voter based political party in the world and has always been about representing the common man. Capitalism was created and performed largely due to the individualism of Europeans. As such, Wagner's Law represents the move of many Europeans towards liberalism both socially and fiscally. Even if Europeans believe themselves to be conservatives, they still are part of a trend of increasing social and fiscal liberalism consciously or not. Rather exemplary are the three presidents of the progressive era. All racially European. All fiscally and socially progressive with respect to their era. Thus, white privilege is largely the benefits of individualism and the increased capability to have stronger political power as either a liberal or a conservative.
White Privilege Theorem:
(group theory), A theorem which proves that, given Plato's forms demonstrating the barrier between the abstract and the concrete, the Lindy effect supporting the Democrats because they are the oldest lasting voter based political party in the planet, the Fundamental theorem of calculus supporting the category fiscal being a derivative of the category social and their integration with their common category of liberalism, as well Europeans being privileged due to being the evolutionary derivative of all other races, and the physics of entropy barring the concrete from the abstract, and Wagner's Law further exemplifying the Fundamental Theorem of Calculus, the Europeans have a privilege that they can either use for progress or regress of civilization.
https://www.amazon.com/gp/aw/d/B0BQG94G2P?ref_=dbs_p_pwh_awm_anx_cl_1&storeType=ebooks.
As the ancestral homeland of our species, Africa contains elevated levels of genetic diversity and substantial population structure. Importantly, African genomes are heterogeneous: they contain mixtures of multiple ancestries, each of which have experienced different evolutionary histories. In this review, we view population genetics through the lens of admixture, highlighting how multiple demographic events have shaped African genomes. Each of these historical vignettes paints a recurring picture of population divergence followed by secondary contact. First, we give a brief overview of African genetic variation and examine deep population structure within Africa, including evidence of ancient introgression from archaic "ghost" populations. Second, we describe the genetic legacies of admixture events that have occurred during the past 10,000 years. This includes gene flow between different click-speaking Khoe-San populations, the stepwise spread of pastoralism from eastern to southern Africa, multiple migrations of Bantu speakers across the continent, as well as admixture from the Middle East and Europe into the Sahel region and North Africa. Furthermore, the genomic signatures of more recent admixture can be found in the Cape Peninsula and throughout the African diaspora. Third, we highlight how natural selection has shaped patterns of genetic variation across the continent, noting that gene flow provides a potent source of adaptive variation and that selective pressures vary across Africa. Finally, we explore the biomedical implications of African population genetic structure on health and disease and call for more ethically conducted studies of African genetic variation.
Genotype-phenotype correlation data covering all ages of Wilson's disease onset in Caucasian patients are limited. We therefore analyzed genotype-phenotype correlations in a retrospective cohort of Finnish patients. Six homozygous (HoZ) and 11 compound heterozygous (CoHZ) patients were included. There were no differences in the presence/absence of hepatic, neurological, psychiatric or any symptoms at diagnosis (p > 0.30 for all) between HoZ and CoHZ patients, but HoZ patients had an earlier age of diagnosis (median 6.7 versus 34.5; p = 0.003). Severe liver affliction was almost exclusively associated with the p.H1069Q variant. Patients with p.H1069Q had a later mean age of diagnosis (30.2 ± 11.6 vs. 8.7 ± 4.9 years; p < 0.001) compared to those without. There were no differences in the presence/absence of hepatic, neurological, psychiatric or any symptoms at diagnosis between p.H1069Q-positive and p.H1069Q-negative patients (p > 0.54 for all). These results suggest that population-specific factors may partly explain the high clinical variability of Wilson's disease.
The biological adaptation of the human lineage to its environment is a recurring question in paleoanthropology. Particularly, how eco‐geographic factors (e.g., environmental temperature and humidity) have shaped upper airway morphology in hominins have been subject to continuing debate. Nasal shape is the result of many intertwined factors that include, but are not limited to, genetic drift, sexual selection, or adaptation to climate. A quantification of nasal airway (NA) morphological variation in modern human populations is crucial to better understand these multiple factors. In the present research, we study 195 in vivo CT scans of adult individuals collected in five different geographic areas (Chile, France, Cambodia, Russia, and South Africa). After segmentation of the nasal airway, we reconstruct 3D meshes that are analyzed with a landmark‐free geometric morphometrics method based on surface deformation. Our results highlight subtle but statistically significant morphological differences between our five samples. The two morphologically closest groups are France and Russia, whose NAs are longer and narrower, with an important protrusion of the supero‐anterior part. The Cambodian sample is the most morphologically distinct and clustered sample, with a mean NA that is wider and shorter. On the contrary, the Chilean sample form the most scattered cluster with the greatest intra‐population variation. The South African sample is morphologically close to the Cambodian sample, but also partially overlaps the French and Russian variation. Interestingly, we record no correlation between NA volume and geographic groups, which raises the question of climate‐related metabolic demands for oxygen consumption. The other factors of variation (sex and age) have no influence on the NA shape in our samples. However, NA volume varies significantly according both to sex and age: it is higher in males than in females and tends to increase with age. In contrast, we observe no effect of temperature or humidity on NA volume. Finally, we highlight the important influence of asymmetries related to nasal septum deviations in NA shape variation. Nasal shape is the result of many intertwined factors, including genetic drift and climatic adaptation. In this study, we quantify nasal airway morphological variation on 195 CT scans of five modern human populations. Our results highlight shape differences between these samples. This shape variation is, however, not correlated with a volume variation, which raises questions about climate‐related energetics demands. Other factors of variation influence internal nasal morphology (i.e., sex, age).
Background
The frequency of Huntington’s disease (HD) may vary considerably, with higher estimates in non-Asian populations. We have recently examined the prevalence of HD in the southern part of Sardinia, a large Italian Mediterranean island that is considered a genetic isolate. We observed regional microgeographic differences in the prevalence of HD across the study area similar to those recently reported in other studies conducted in European countries. To explore the basis for this variability, we undertook a study of the incidence of HD in Sardinia over a 10-year period, 2009 to 2018.Methods
Our research was conducted in the 5 administrative areas of Sardinia island. Case patients were ascertained through multiple sources in Sardinia and Italy.ResultsDuring the incidence period 53 individuals were diagnosed with clinically manifested HD. The average annual incidence rate 2009–2018 was 2.92 per 106 persons-year (95% CI, 2.2 to 3.9). The highest incidence rate was observed in South Sardinia (6.3; 95% CI, 4.2–9.5). This rate was significantly higher (p<0.01) than the rates from Cagliari, Oristano, and Sassari provinces but did not significantly differ (p = 0.38) from the Nuoro rate.Conclusions
The overall incidence of HD in Sardinia is close to the correspondent estimates in Mediterranean countries. Our findings highlight also the possibility of local microgeographic variations in the epidemiology of HD that might reflect several factors, including a possible founder effect in the rural areas of South Sardinia and Nuoro.
Compared to the rest of the African continent, North Africa has provided limited genomic data. Nonetheless, the genetic data available show a complex demographic scenario characterized by extensive admixture and drift. Despite the continuous gene flow from the Middle East, Europe, and sub-Saharan Africa, an autochthonous genetic component is still present in North African groups that dates back to pre-Holocene times. The comparison of ancient and modern genomes has evidenced a genetic continuity in the region since Epipaleolithic times. Later population movements, especially the gene flow from the Middle East associated with the Neolithic, have diluted the genetic autochthonous component, creating an east to west gradient. Recent historical movements, such as the Arabization, have also contributed to the genetic landscape observed currently in North Africa and have culturally transformed the region. Genome analyses have not shown evidence of a clear correlation between cultural and genetic diversity in North Africa, as there is no genetic pattern of differentiation between Tamazight (i.e. Berber) and Arab speakers as a whole. Besides the gene flow received from neighboring areas, the analysis of North African genomes has shown that the region has also acted as a source of gene flow since ancient times. As a result of the genetic uniqueness of North African groups and the lack of available data, there is an urgent need for the study of genetic variation in the region and its implications in health and disease.
Background and purpose. The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 × 10 5 to 10.8 × 10 5. Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate.
Methods. The study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy.
Results. We identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 × 10 5 in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 × 10 5 vs. 3.0 × 10 5, p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 ± 2.1 vs. 17.7 ± 2.2, p = 0.5).
Conclusions. The overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.
Background
Data on the epidemiology and prognosis of Wilson's disease are scarce, and no clinical data are available from Finland.
Methods
All persons diagnosed and treated for Wilson's disease in Finnish hospitals in 1998 to 2017 were identified. Data were collected from national registries and patient charts.
Results
The point prevalence was 0.45/100,000 (95% confidence interval, 0.29–0.67) on December 31, 2017, but no more than 0.35/100,000 (95% confidence interval, 0.21–0.55) among native Finns. Annual incidence was 0.016/100,000 (95% confidence interval, 0.0093–0.026). Median age at diagnosis was 15.8 years (interquartile range, 8.3–32.2; range, 3.8–48.1 years). Upon presentation, liver damage was observed in 58%, neurological signs and symptoms (most often tremor and dysarthria) in 40%, and 32% of patients were asymptomatic. Patients had poorer long‐term survival (hazard ratio, 2.92 for death; P = 0.005) compared with matched controls.
Conclusions
Wilson's disease is very rare in Finland. Patients have an increased risk of death indicating an unmet treatment need.
Finland is a high‐risk region for multiple sclerosis (MS) with several epidemiological studies on the subject published since 1964 but these have not been comprehensively scrutinized. The objective of this study was to review previous studies of Finnish MS epidemiology, introduce new data on MS prevalence in western parts of Finland and do further analyses on data from previous studies. We performed a systematic search on articles regarding MS epidemiology in Finland in PubMed database and all relevant articles were included in this review. MS prevalences in the western hospital districts of Vaasa, South Ostrobothnia and Pirkanmaa were calculated in 1980‐2007 by using previously unpublished data obtained from a retrospective search from hospital administrative registries. To enhance comparability of the epidemiological figures, we calculated age‐standardized prevalence of MS from the new data from western hospital districts and previous data from North Ostrobothnia, Southwest Finland and North Karelia. Marked regional differences in MS epidemiology were confirmed with concentration of the disease in the western and southwestern parts of the country. The highest regional age‐standardized MS prevalence of 288/100 000 was reported in South Ostrobothnia in 2007. A clear and stable increase in MS prevalence was observed through the decades but the only marked increase in incidence happened in 1990s. Methodological differences hampered direct comparisons of different studies, highlighting the importance of common principles of reporting and standardizing the epidemiological figures. More comprehensive studies on MS epidemiology are still warranted to yield important information concerning the aetiology of the disease.
Background Children of Sardinian heritage are at high risk of type 1 diabetes, whereas no data are available in young adults. Age at onset of type 1 diabetes could be associated with different relative weight of genetic susceptibility and environmental determinants in the pathogenesis of the disease. We test this hypothesis in subjects with Sardinian heritage 0–29 years of age living in the city of Turin, a highly industrialized area in Northern Italy.
Methods In all, 202 cases with onset of type 1 diabetes aged 0–29 years during 1984–1991 and 1010 controls randomly selected from residents of the city of Turin, frequency-matched by sex and year of birth to cases, were included in this study. Name and place of birth of parents were ascertained by postal inquiry and linkage with city population and census files. Social class was based on the highest educational level of parents abstracted from 1991 and 1981 census files.
Results Differential effects on risk of type 1 diabetes of Sardinian heritage and social class in the age groups 0–14 and 15–29 years were found. In children with one and both Sardinian parents the odds ratios (OR) were 2.09 (95% CI : 0.85–5.15) and 3.20 (95% CI : 0.75–13.64); in young adults 0.81 (95% CI : 0.18–3.64) and 1.95 (95% CI : 0.51–7.40), respectively. In subjects with low social class the OR were 1.16 (95% CI : 0.68–1.97) in children and 0.66 (95% CI : 0.41–1.05) in young adults.
Conclusions This study shows higher risk of type 1 diabetes in subjects of Sardinian heritage; higher risk in children than in young adults and a protective effect of low social class in young adults. These findings are consistent with the hypothesis of heterogeneity of type 1 diabetes by age at onset, with prevailing genetic effect in childhood and environmental determinants in adulthood.
The genetic mechanism of MHC polymorphism generation is a controversial issue and it has been supposed to vary from locus to locus [1,2]. Recombination mechanisms (gene duplication, gene conversion, inter-allelic/inter-locus sequence exchange) and point mutations are thought to have played different roles during the evolution of the various HLA class II loci [3–5]. In this respect, recombination events promoted by conserved χ-like putative recombination signals, found in HLA-DRB 1 and -DPB 1 genes between the β-sheet and α-helix domains, are believed to have significantly contributed to polymorphism generation at these loci [5,6]. By contrast, the fact that χ-like sequences have not been observed at the DQB1 locus has been put forward to explain why recombination-like events are less frequently seen at this locus where point mutations are considered to have played the major role in polymorphism generation [1]. We indicate that a χ-like sequence is also present within the DQB1 locus (5’-GCTGGGG-3’, nucleotide position 156–162) and that this motif may have contributed, through intralocus gene conversion, to the generation of the novel DQB 1 *0305 allele.
A bibliography of material relating to the use of DNA in human identification is presented. It includes bibliographies previously compiled by the author and other individuals, the DNA Legal Assistance Subunit of the FBI, and references from all the chapters in this volume.
Language is the expression of human communication through which knowledge, belief, and behavior can be experienced, explained, and shared. What are the origins of language? How did language develop? Who were the first characters the first in human history to use language? What disorders/diseases are associated with speech and language?
This research evaluates these issues from a contemporary viewpoint. The Biblical text was examined and verses related to language development in humans were studied closely.
Migration is a widespread human activity dating back to the origin of our species. Advances in genetic sequencing have greatly increased our ability to track prehistoric and historic population movements and allowed migration to be described both as a biological and socioeconomic process. Presenting the latest research, Causes and Consequences of Human Migration provides an evolutionary perspective on human migration past and present. Crawford and Campbell have brought together leading thinkers who provide examples from different world regions, using historical, demographic and genetic methodologies, and integrating archaeological, genetic and historical evidence to reconstruct large-scale population movements in each region. Other chapters discuss established questions such as the Basque origins and the Caribbean slave trade. More recent evidence on migration in ancient and present day Mexico is also presented. Pitched at a graduate audience, this book will appeal to anyone with an interest in human population movements.
The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Eu-rope, is however missing. In the present study we show genetic information on ancient populations of the SouthEast of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Câr-cea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from NorthWest Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.
Stable genetic background makes individuals from the Mediterranean island of Sardinia ideal to define the predictive power of islet-related autoantibodies (IRAs): glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase-like antibodies (IA-2A), islet cell antibodies (ICA) to identify T1DM progressors. The aims of the present study were: (1) determination of IRAs reference limits in healthy non-diabetic Sardinian schoolchildren (SSc). (2) Predictive power evaluation of IRAs as single or combined determination to identify islet to identify T1DM progressors.
Between 1986 and 1994, 8448 SSc were tested for IRAs. All were followed up for 10 years. The predictive power of single or combination of IRAs was determined as hazard ratio (HR), sensitivity, specificity, area under the ROC curve, negative and positive predictive value (NPV, PPV).
All 43 progressors to T1DM, but three showed at least one autoantibody positivity. HR for any single-autoantibody positivity was 55.3 times greater when compared to SSc negative for all IRAs. Any single autoantibody performed at least 64.9 % sensitivity with PPV always lower than 16 %. The best performing combination was ICA, plus IA-2A (showing 52.6 % sensitivity, 99.8 % specificity, 0.76 area under the ROC curve, 51.3 % PPV and 99.8 % NPV.
Determination of IRAs reference limits in healthy SSc by standard statistical methods is crucial to establish the power of IRAs as progression markers to T1DM. Our data offer a solid rationale for future testing of ICA and IA-2A as routine laboratory markers to identify individuals at high risk of T1DM in the general population.
S cientists' perceptions of their discipline clearly in-fluence how they frame their research agenda. See-ing bioarchaeology as anthropology profoundly affects the problems that capture one's interest, the questions that one seeks to answer, and the methods one uses to resolve them. Bioarchaeology as anthropology reaffirms a worldview that incorporates an intradisciplinary biocultural approach with a cross-cultural perspective. The field is committed to understanding the adaptation and the evolution of social systems. Given the post-processual rejection of cultural evolutionary theory, re-jection of scientific methodology, rejection of culture as a means of extrasomatic adaptation, rejection of culture as a system, rejection of ecological interpre-tations, and rejection of etic analysis (Johnson 1999), the perspective presented in this chapter may be seen as a defense of an earlier era of scientific anthropology. Emotionally, a rejection of the postprocessual criticism may feel like the best response; however, a reasoned evaluation of the criticism and measured response is a much more effective strategy. This strategy is reflected in Charles and Buikstra's (2001) effective use of "miti-gated objectivism" championed by Wylie (1992). I will argue that bioarchaeology as anthropology, by incorpo-rating aspects of the postprocessual and antiprocessual critiques, has positioned itself to make new and sig-nificant contributions to knowledge. In this essay, I have two objectives. The first is to discuss the development of bioarchaeology (Larsen 1987, 1997) from within anthropology at the time the discipline espoused a four-field approach. The sec-ond objective is to demonstrate the usefulness of an intradisciplinary bioarchaeology in understanding problems in contemporary human adaptation. Specifi-cally, I will suggest how the post-Neolithic transfor-mation may play a role in helping us understand health problems related to diet and disease in contemporary society.
Aim:
Functional polymorphism ER22/23EK glucocorticoid receptor leads to reduction of its resistance and to increase in its sensitivity to the glucocorticoid that regulate the functioning of the axis hypothalamus - pituitary - adrenal glands. Disturbances in the regulation of this axis are observed in patients with psychiatric disorders. The aim of this study was to demonstrate the association ER22/23EK polymorphism with bipolar disorder and major depressive disorders.
Methods:
In the study 144 patients with unipolar disorders and 479 patients with bipolar disorder were included. Patients were diagnosed by two psychiatrists on the basis of medical records and interview based on SCID criteria (Structured Clinical Interview for DSM Disorders). The control group comprised 595 healthy subjects. As the research material peripheral blood was used, from which DNA was obtained. Genotyping was performed using PCR - RFLP method.
Results:
No association of ER22/23EK polymorphism with unipolar disorder or with bipolar disorder was found. GA genotype was not observed in any of the subjects.
Conclusion:
ER22/23EK functional polymorphism of the glucocorticoid receptor gene is not associated with unipolar and bipolar disorder.
Background To study the epidemiology of childhood-onset type 1 insulin-dependent diabetes in Europe, the EURODIAB collaborative group established in 1988 prospective geographically-defined registers of new cases diagnosed under 15 years of age. This report is based on 16 362 cases registered during the period 1989—94 by 44 centres representing most European countries and Israel and covering a population of about 28 million children. Methods Multiple sources of ascertainment were used in most centres to validate the completeness of registration by the capture-recapture method. Trends in incidence during the period were analysed by Poisson regression, the data from centres within each country being pooled. Findings The standardised average annual incidence rate during the period 1989—94 ranged from 3.2 cases per 100 000 per year in the Former Yugoslav Republic of Macedonia to 40.2 cases per 100 000 per year in two regions of Finland. By pooling over centres, the annual rate of increase in incidence was 3.4% (95% Cl 2.5—4.4%), but in some central European countries it was more rapid than this. Pooled over centres and sexes, the rates of increase were 6.3% (4.1—8.5%) for children aged 0—4 years, 3.1% (1.5—4.8%) for 5—9 years, and 2.4% (1.0—3.8%) for 10—14 years. Interpretation The results confirm a very wide range of incidence rates within Europe and show that the increase in incidence during the period varied from country to country. The rapid rate of increase in children aged under 5 years is of particular concern.
The HLA haplotype B18-DR3 has a widespread geographical distribution, but has its greatest frequencies in Southern Europe, probably vestigial of the earliest populations of this region, particularly in the Pays Basque and Sardinia. This haplotype is of medical significance, being that most implicated as a factor of risk in insulin-dependent diabetes mellitus. In this study, the closely linked microsatellite markers (TNFa,b,c) in the region of the tumor necrosis factor (TNF) genes have been used in an attempt to subtype this haplotype in the two populations and/or in healthy and diabetic populations. A total of 79 HLA-B18-DR3 haplotypes were analyzed: 54 in Basques (12 from healthy individuals and 42 from diabetics or their first-degree relatives) and 25 in Sardinians (13 from healthy and 13 from diabetic individuals). The TNF haplotype a1-b5-c2 is completely associated with B18-DR3 in both populations. The homogeneity of the B18-DR3 haplotype in two ethnically pure populations implies stability in evolution, which suggest that the mutation rate of these microsatellite markers must be less than is usually assumed (i.e., {approximately} 5x10{sup {minus}6} per site per generation). Such markers should be powerful tools for studying genetic drift and admixture of populations, but it remains to be established whether this stability is a rule for all microsatellites in HLA haplotypes or whether or whether it is restricted to some microsatellites and/or some HLA haplotypes. The population genetics of those microsatellites associated with HLA B18-DR3 was also studied in a random sample of the Basque population. 44 refs., 3 tabs.
Le polymorphisme des gènes HLA-DRB1 et HLA-DQB1 a été étudié, chez 100 Algériens non apparentés originaires d'Alger, par P.C.R et oligosondes spécifiques de séquence. Comparée aux populations d'Europe Occidentale, cette population se caractérise par une fréquence haplotypique plus élevée des DRB1*03-DQB1*0201 (21,5 %) et une fréquence moins élevée des DRB1*0101-DQB1*0501 (2 %). Deux haplotypes inattendus ont été observés: DRB1*07-DQB1*0301 et DRB1*0406-DQB1*0402. DRB1*0402 est le sous-type DRB1*04 le plus fréquent. De plus l'étude de ces sujets nous a permis de mettre en évidence un rare allèle DQB1*0305 décrit uniquement chez un sujet sarde à ce jour.
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