RESUMO
PURPOSE: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center. METHODS: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria. RESULTS: The WERA matrix overlooked an active screening area of 821 postal code areas - representing about 50 % of Bavaria´s spatial expansion and more than six million inhabitants. The WERA matrix identified regions successfully connected to our outreach structures in terms of subsidiarity - with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog - characterized by high levels of cancer care performed by WERA and low levels or no MTB representation. CONCLUSIONS: The WERA matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers.
Assuntos
Acessibilidade aos Serviços de Saúde , Oncologia , Neoplasias , Medicina de Precisão , Humanos , Alemanha , Acessibilidade aos Serviços de Saúde/organização & administração , Neoplasias/terapia , Oncologia/organização & administração , Institutos de Câncer/organização & administração , População RuralRESUMO
A 5,000-year-old Yersinia pestis genome (RV 2039) is reconstructed from a hunter-fisher-gatherer (5300-5050 cal BP) buried at Rinnukalns, Latvia. RV 2039 is the first in a series of ancient strains that evolved shortly after the split of Y. pestis from its antecessor Y. pseudotuberculosis â¼7,000 years ago. The genomic and phylogenetic characteristics of RV 2039 are consistent with the hypothesis that this very early Y. pestis form was most likely less transmissible and maybe even less virulent than later strains. Our data do not support the scenario of a prehistoric pneumonic plague pandemic, as suggested previously for the Neolithic decline. The geographical and temporal distribution of the few prehistoric Y. pestis cases reported so far is more in agreement with single zoonotic events.
Assuntos
Peste/microbiologia , Yersinia pestis/fisiologia , Humanos , Letônia , Funções Verossimilhança , FilogeniaRESUMO
Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years, is one of the most devastating recorded in human history. To investigate the potential impact of Y. pestis on human immunity genes, we extracted DNA from 36 plague victims buried in a mass grave in Ellwangen, Germany in the 16th century. We targeted 488 immune-related genes, including HLA, using a novel in-solution hybridization capture approach. In comparison with 50 modern native inhabitants of Ellwangen, we find differences in allele frequencies for variants of the innate immunity proteins Ficolin-2 and NLRP14 at sites involved in determining specificity. We also observed that HLA-DRB1*13 is more than twice as frequent in the modern population, whereas HLA-B alleles encoding an isoleucine at position 80 (I-80+), HLA C*06:02 and HLA-DPB1 alleles encoding histidine at position 9 are half as frequent in the modern population. Simulations show that natural selection has likely driven these allele frequency changes. Thus, our data suggest that allele frequencies of HLA genes involved in innate and adaptive immunity responsible for extracellular and intracellular responses to pathogenic bacteria, such as Y. pestis, could have been affected by the historical epidemics that occurred in Europe.
Assuntos
Peste , Yersinia pestis , DNA , Genômica , Humanos , Pandemias/história , Peste/genética , Yersinia pestis/genéticaRESUMO
Medieval Europe was repeatedly affected by outbreaks of infectious diseases, some of which reached epidemic proportions. A Late Medieval mass burial next to the Heiligen-Geist-Hospital in Lübeck (present-day Germany) contained the skeletal remains of more than 800 individuals who had presumably died from infectious disease. From 92 individuals, we screened the ancient DNA extracts for the presence of pathogens to determine the cause of death. Metagenomic analysis revealed evidence of Salmonella enterica subsp. enterica serovar Paratyphi C, suggesting an outbreak of enteric paratyphoid fever. Three reconstructed S. Paratyphi C genomes showed close similarity to a strain from Norway (1200 CE). Radiocarbon dates placed the disease outbreak in Lübeck between 1270 and 1400 cal CE, with historical records indicating 1367 CE as the most probable year. The deceased were of northern and eastern European descent, confirming Lübeck as an important trading center of the Hanseatic League in the Baltic region.
RESUMO
The historical phylogeography of Ostrea edulis was successfully depicted in its native range for the first time using ancient DNA methods on dry shells from museum collections. This research reconstructed the historical population structure of the European flat oyster across Europe in the 1870s-including the now extinct population in the Wadden Sea. In total, four haplogroups were identified with one haplogroup having a patchy distribution from the North Sea to the Atlantic coast of France. This irregular distribution could be the result of translocations. The other three haplogroups are restricted to narrow geographic ranges, which may indicate adaptation to local environmental conditions or geographical barriers to gene flow. The phylogenetic reconstruction of the four haplogroups suggests the signatures of glacial refugia and postglacial expansion. The comparison with present-day O. edulis populations revealed a temporally stable population genetic pattern over the past 150 years despite large-scale translocations. This historical phylogeographic reconstruction was able to discover an autochthonous population in the German and Danish Wadden Sea in the late nineteenth century, where O. edulis is extinct today. The genetic distinctiveness of a now-extinct population hints at a connection between the genetic background of O. edulis in the Wadden Sea and for its absence until today.
Assuntos
Ostrea/genética , Animais , Ostrea/classificação , Filogenia , Refúgio de Vida SelvagemRESUMO
The Wartberg culture (WBC, 3500-2800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We performed genome-wide analyses of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3300-3200 cal. BCE). The results showed that the farming population of Niedertiefenbach carried a surprisingly large hunter-gatherer ancestry component (34-58%). This component was most likely introduced during the cultural transformation that led to the WBC. In addition, the Niedertiefenbach individuals exhibited a distinct human leukocyte antigen gene pool, possibly reflecting an immune response that was geared towards detecting viral infections.
Assuntos
Agricultura , Comportamento Alimentar/fisiologia , Antígenos HLA/genética , Comportamento Predatório/fisiologia , Animais , Arqueologia , DNA Antigo/análise , Europa (Continente) , Evolução Molecular , Variação Genética , Genética Populacional , Genoma Humano , Estudo de Associação Genômica Ampla , Alemanha , História Antiga , Migração Humana , Humanos , Polimorfismo de Nucleotídeo Único , Grupos Raciais/genética , Características de ResidênciaRESUMO
Ancient genomic studies have identified Yersinia pestis (Y. pestis) as the causative agent of the second plague pandemic (fourteenth-eighteenth century) that started with the Black Death (1,347-1,353). Most of the Y. pestis strains investigated from this pandemic have been isolated from western Europe, and not much is known about the diversity and microevolution of this bacterium in eastern European countries. In this study, we investigated human remains excavated from two cemeteries in Riga (Latvia). Historical evidence suggests that the burials were a consequence of plague outbreaks during the seventeenth century. DNA was extracted from teeth of 16 individuals and subjected to shotgun sequencing. Analysis of the metagenomic data revealed the presence of Y. pestis sequences in four remains, confirming that the buried individuals were victims of plague. In two samples, Y. pestis DNA coverage was sufficient for genome reconstruction. Subsequent phylogenetic analysis showed that the Riga strains fell within the diversity of the already known post-Black Death genomes. Interestingly, the two Latvian isolates did not cluster together. Moreover, we detected a drop in coverage of the pPCP1 plasmid region containing the pla gene. Further analysis indicated the presence of two pPCP1 plasmids, one with and one without the pla gene region, and only one bacterial chromosome, indicating that the same bacterium carried two distinct pPCP1 plasmids. In addition, we found the same pattern in the majority of previously published post-Black Death strains, but not in the Black Death strains. The pla gene is an important virulence factor for the infection of and transmission in humans. Thus, the spread of pla-depleted strains may, among other causes, have contributed to the disappearance of the second plague pandemic in eighteenth century Europe.
Assuntos
Proteínas de Bactérias/genética , Genoma Bacteriano , Peste/microbiologia , Ativadores de Plasminogênio/genética , Yersinia pestis/genética , DNA Bacteriano/genética , Epidemias , Europa (Continente)/epidemiologia , Humanos , Metagenoma , Pandemias , Peste/epidemiologia , Virulência/genética , Yersinia pestis/isolamento & purificaçãoRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ'≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Admixture estimates obtained by a maximum likelihood method using HLA-A/-B/-DRB1 as genetic estimators revealed that the main genetic components in Mexico as a whole are Native American (ranging from 37.8% in the northern part of the country to 81.5% in the southeastern region) and European (ranging from 11.5% in the southeast to 62.6% in northern Mexico). African admixture ranged from 0.0 to 12.7% not following any specific pattern. We were able to detect three major immunogenetic clusters correlating with genetic diversity and differential admixture within Mexico: North, Central and Southeast, which is in accordance with previous reports using genome-wide data. Our findings provide insights into the population immunogenetic substructure of the whole country and add to the knowledge of mixed ancestry Latin American population genetics, important for disease association studies, detection of demographic signatures on population variation and improved allocation of public health resources.
Assuntos
Alelos , Genética Populacional/métodos , Antígenos HLA/genética , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único , DNA/genética , DNA/isolamento & purificação , Frequência do Gene , Genoma Humano , Haplótipos , Humanos , Desequilíbrio de Ligação , MéxicoRESUMO
The forced relocation of several thousand Africans during Mexico's historic period has so far been documented mostly through archival sources, which provide only sparse detail on their origins and lived experience. Here, we employ a bioarchaeological approach to explore the life history of three 16th century Africans from a mass burial at the San José de los Naturales Royal Hospital in Mexico City. Our approach draws together ancient genomic data, osteological analysis, strontium isotope data from tooth enamel, δ13C and δ15N isotope data from dentine, and ethnohistorical information to reveal unprecedented detail on their origins and health. Analyses of skeletal features, radiogenic isotopes, and genetic data from uniparental, genome-wide, and human leukocyte antigen (HLA) markers are consistent with a Sub-Saharan African origin for all three individuals. Complete genomes of Treponema pallidum sub. pertenue (causative agent of yaws) and hepatitis B virus (HBV) recovered from these individuals provide insight into their health as related to infectious disease. Phylogenetic analysis of both pathogens reveals their close relationship to strains circulating in current West African populations, lending support to their origins in this region. The further relationship between the treponemal genome retrieved and a treponemal genome previously typed in an individual from Colonial Mexico highlights the role of the transatlantic slave trade in the introduction and dissemination of pathogens into the New World. Putting together all lines of evidence, we were able to create a biological portrait of three individuals whose life stories have long been silenced by disreputable historical events.
Assuntos
DNA Antigo/análise , Pessoas Escravizadas/história , Nível de Saúde , Hepatite B/história , Bouba/história , Adulto , Arqueologia , População Negra/história , Vírus da Hepatite B/isolamento & purificação , História do Século XVI , Humanos , Masculino , México , Treponema/isolamento & purificação , Adulto JovemRESUMO
The Cucuteni-Trypillia complex (CTC) flourished in eastern Europe for over two millennia (5100-2800 BCE) from the end of the Neolithic to the Early Bronze Age. Its vast distribution area encompassed modern-day eastern Romania, Moldova and western/central Ukraine. Due to a lack of existing burials throughout most of this time, only little is known about the people associated with this complex and their genetic composition. Here, we present genome-wide data generated from the skeletal remains of four females that were excavated from two Late CTC sites in Moldova (3500-3100 BCE). All individuals carried a large Neolithic-derived ancestry component and were genetically more closely related to Linear Pottery than to Anatolian farmers. Three of the specimens also showed considerable amounts of steppe-related ancestry, suggesting influx into the CTC gene-pool from people affiliated with, for instance, the Ukraine Mesolithic. The latter scenario is supported by archaeological evidence. Taken together, our results confirm that the steppe component arrived in eastern Europe farming communities maybe as early as 3500 BCE. In addition, they are in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations.
Assuntos
Arqueologia , Fluxo Gênico , Genética Populacional , Migração Humana , Europa Oriental , Feminino , Genoma Humano , Humanos , MasculinoRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 173 Mexicans from the state of Chiapas living in the city of Tuxtla Gutiérrez (Nâ¯=â¯52) and rural communities (Nâ¯=â¯121), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in Chiapas include 12 Native American and one European haplotype. Admixture estimates revealed that the main genetic components in Chiapas are Native American (71.61⯱â¯0.58% by ML; 53.16% of Native American haplotypes) and European (26.39⯱â¯5.05% by ML; 25.86% of European haplotypes), and a less prominent African genetic component (2.00⯱â¯5.20% by ML; 9.77% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Cidades , Frequência do Gene , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 122 Mexicans from the state of Hidalgo living in the city of Pachuca (Nâ¯=â¯41) and rural communities (Nâ¯=â¯81), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in Hidalgo include eight Native American and one European haplotypes. Admixture estimates revealed that the main genetic components in Hidalgo are Native American (58.93⯱â¯2.16% by ML; 54.51% of Native American haplotypes) and European (32.49⯱â¯2.88% by ML; 28.69% of European haplotypes), and a relatively high African genetic component (8.58⯱â¯0.93% by ML; 6.97% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Frequência do Gene , Genótipo , Geografia , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 81 Mexicans from the state of Campeche living in the city of Campeche (Nâ¯=â¯34) and rural communities (Nâ¯=â¯47), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Campeche include ten Native American, three European, one African and one Asian haplotype. Admixture estimates revealed that the main genetic components in the state of Campeche are Native American (65.56⯱â¯0.96% by ML; 51.24% of Native American haplotypes), European (34.44⯱â¯10.94% by ML; 30.25% of European haplotypes), and a virtually absent African genetic component (0.00⯱â¯10.31% by ML; 9.26% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Cidades , Frequência do Gene , Genótipo , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 112 Mexicans from the state of Morelos living in the city of Cuernavaca (Nâ¯=â¯82) and rural communities (Nâ¯=â¯30), to obtain information regarding allelic and haplotypic frequencies. The most frequent haplotypes in Morelos include seven Native American, one European, one African and one Asian haplotype. Admixture estimates revealed that the main genetic components in Morelos are Native American (60.43⯱â¯2.22% by ML; 53.57% of Native American haplotypes) and European (39.58⯱â¯3.70% by ML; 27.68% of European haplotypes), and a virtually absent African genetic component (0.00⯱â¯4.93% by ML; but 11.16% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Frequência do Gene , Genótipo , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 224 Mexicans from the state of Tabasco living in the city of Villahermosa (Nâ¯=â¯82) and rural communities (Nâ¯=â¯142), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in Tabasco include 13 Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in Tabasco are Native American (67.79⯱â¯1.59% by ML; 56.25% of Native American haplotypes) and European (27.21⯱â¯3.97% by ML; 29.91% of European haplotypes), and a less prominent African genetic component (5.01⯱â¯4.42% by ML; 8.93% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Cidades , Frequência do Gene , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 88 Mexicans from the state of Querétaro living in the city of Querétaro (Nâ¯=â¯45) and rural communities (Nâ¯=â¯43), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Querétaro include seven Native American, two European and one Asian haplotype. Admixture estimates revealed that the main genetic components in the state of Querétaro are Native American (51.82⯱â¯4.42% by ML; 42.61% of Native American haplotypes) and European (48.18⯱â¯3.55% by ML; 46.02% of European haplotypes), with a virtually absent African genetic component (0.00⯱â¯4.25% by ML; 4.55% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Frequência do Gene , Genótipo , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1217 Mexicans from the Mexico City Metropolitan Area living in the northern (Nâ¯=â¯751), southern (Nâ¯=â¯52), eastern (Nâ¯=â¯79), western (Nâ¯=â¯33), and central (Nâ¯=â¯152) Mexico City, and rural communities (Nâ¯=â¯150), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes include 11 Native American haplotypes. Admixture estimates revealed that the main genetic components are Native American (63.85⯱â¯1.55% by ML; 57.19% of Native American haplotypes) and European (28.53⯱â¯3.13% by ML; 28.40% of European haplotypes), and a less apparent African genetic component (7.61⯱â¯1.96% by ML; 7.17% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Cidades , Frequência do Gene , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , México , População RuralRESUMO
We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 144 Mexicans from the state of Guerrero to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes in the state of Guerrero include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Guerrero are Native American (61.36⯱â¯2.69% by ML; 54.17% of Native American haplotypes) and European (35.01⯱â¯4.59% by ML; 32.29% of European haplotypes), and a relatively low African genetic component (3.63⯱â¯2.38% by ML; 5.90% of African haplotypes).
Assuntos
Etnicidade/genética , Variação Genética , Genética Populacional , Antígenos HLA/genética , Alelos , Frequência do Gene , Genótipo , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , MéxicoRESUMO
The indigenous populations of inner Eurasia-a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra-harbour tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine and Uzbekistan. We furthermore report additional damage-reduced genome-wide data of two previously published individuals from the Eneolithic Botai culture in Kazakhstan (~5,400 BP). We find that present-day inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries, mirroring geography. The Botai and more recent ancient genomes from Siberia show a decrease in contributions from so-called 'ancient North Eurasian' ancestry over time, which is detectable only in the northern-most 'forest-tundra' cline. The intermediate 'steppe-forest' cline descends from the Late Bronze Age steppe ancestries, while the 'southern steppe' cline further to the south shows a strong West/South Asian influence. Ancient genomes suggest a northward spread of the southern steppe cline in Central Asia during the first millennium BC. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.
Assuntos
Povo Asiático , Fluxo Gênico , Geografia , Humanos , Federação RussaRESUMO
Riemerella anatipestifer is a Gram-negative bacterium belonging to the family Flavobacteriaceae It is primarily associated with acute septicemia in younger birds. The R. anatipestifer isolate 17CS0503 described here was isolated from a Peking duck (Anas platyrhynchos domesticus) in Hannover, Germany, in 1999.