Role of Genetic Ancestry in Oropharyngeal Squamous-Cell Carcinoma: A Cross-Sectional Study in Brazil

Background: HPV infection represents an important etiologic factor for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The different ethnic backgrounds could be related to different susceptibility to Human Papillomavirus (HPV). The aim of our study was to assess the whole of genetic ancestry in HPV status in OPSCC patients. Methods: We conducted a cross-sectional study on patients with OPSCC admitted to the Barretos Cancer Hospital, Brazil from 2014 to 2019. Of these, DNA extraction was performed on 40 patients and genetic ancestry was assessed using a specific panel of 46 informative ancestry markers. Results: We observed a predominance of European ancestry (63%), followed by African (18%), Amerindian (9%) and Asian (8%) both in the OPSCC HPV-positive and HPV-negative group. We did not find any statistically significant differences between the HPV-positive and HPV-negative OPSCC groups in relation to European (p = 0.499), African (p = 0.448), Asian (p = 0.275) or Amerindian (p = 0.836) ancestry. Conclusions: We found a predominance of European ancestry, both in the HPV-positive and HPV-negative groups. In our study, we did not find statistically significant differences between HPV-positive or HPV-negative groups in relation to ancestry.

Pairwise Shared Ancestry in Random-Mating Constant-Size Populations

In a panmictic population of constant size N, random pairs of individuals will have a most recent shared ancestor who lived slightly more than 0.5 log2N generations previously, on average. The probability that a random pair of individuals will share at least one ancestor who lived 0.5 log2N generations ago, or more recently, is about 50%. Those individuals, if they do share an ancestor from that generation, would be cousins of degree (0.5 log2N) - 1. Shared ancestry from progressively earlier generations increases rapidly until there is universal pairwise shared ancestry. At that point, every individual has one or more ancestors in common with every other individual in the population, although different pairs may share different ancestors. Those ancestors lived approximately 0.7 log2N generations in the past, or more recently. Qualitatively, the ancestries of random pairs have about 50% similarity for ancestors who lived about 0.9 log2N generations before the present. That is, about half of the ancestors from that generation belonging to one member of the pair are present also in the genealogy of the other member. Qualitative pairwise similarity increases to more than 99% for ancestors who lived about 1.4 log2N generations in the past. Similar results apply to a metric of quantitative pairwise genealogical overlap.

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

AIM:To study the association between genetic ancestry,non-alcoholic fatty liver disease(NAFLD) metabolic characteristics in two cohorts of patients,from Brazil and Portugal. METHODS:We included 131 subjects from Brazil [(n = 45 with simple steatosis(S. Steatosis) and n = 86 with nonalcoholic steatohepatitis(NASH)] and 90 patients from Portugal(n = 66,S. Steatosis; n = 24,NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis:simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers(AT3-I/D,LPL,Sb19.3,APO,FYNull,PV92,and CKMM) with the greatest ethnicgeographical differential frequencies(≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP onlineand the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant(P < 0.05). RESULTS:In the Brazilian sample,NASH was significantly more frequent among the elderly patients with diabetes(NASH 56 ± 1.1 years old vs S. Steatosis 51 ± 1.5 years old,P = 3.7 x 10-9),dyslipidemia(NASH 63% vs S. Steatosis 37%,P = 0.009),higher fasting glucose levels(NASH 124 ± 5.2 vs S. Steatosis 106 ± 5.3,P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3(70.8%) vs S. Steatosis 4.6(29.2%) P = 0.04]. In the Portuguese study population,dyslipidemia was present in all patients with NASH(P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group(P = 0.003,respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort(Brazilian cohort:P = 0.75; Portuguese cohort:P = 0.97). Nonetheless,the genetic ancestry contribution of the Brazilian and Portuguese population were different,and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups.CONCLUSION:There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.

The Future Common Ancestry of All Present-Day Humans

At some future time, each person alive today will be either an ancestor of everyone or an ancestor of no one. If the global population were unstructured by geography, race, religion and other factors, the time to future common ancestry for present-day humans would be between 33 and 66 generations, or about 1000 - 2000 years. In a structured population, migration and intermarriage are the necessary conditions for global common ancestry. Simulation of random and hierarchical migration models, shows that time to future global ancestry is generally less than triple, and often less than twice, that required for an unstructured population. The models suggest that someone alive today will become a common ancestor of the entire world population by about 5000 CE, or sooner;and that all current humans who are destined to become global common ancestors will be so by about 8000 CE, or sooner. At which time, everybody then alive will have the exact same genealogical ancestors from the present day.

Pairwise Shared Genealogical Ancestry in Structured Populations

Simulation was used to investigate the effects of population structure and migration on metrics of pairwise shared ancestry. Random and hierarchical structures, or migration geometries, were examined. Compared to panmictic populations, progress to all qualitative metrics of pairwise ancestry is delayed in structured populations. However, unless migration is very low, the time required is generally less than triple and often less than twice that required in a panmictic population of the same total size. Population structure also increases, to a similar degree, the time required for a population-wide most recent common ancestor (MRCA). As a result, the relationships between various qualitative metrics of pairwise shared ancestry and MRCA time are relatively unaffected by population structure. For example, the mean time to most recent shared ancestor (MRSA) with global sampling of pairs is 40% - 50% of the MRCA time for almost all simulated structures and migration levels. Quantitative pairwise genealogical overlap is strongly affected by population structure. With global sampling, pairwise quantitative overlap never approaches 1.0, as it does in panmictic populations;and instead eventually becomes stationary at much lower values. Possible implications of the present results for human pairwise shared ancestry are discussed. For globally sampled pairs, the longest time to most recent shared ancestor (MRSA) for humans is suggested to be approximately 2100 years before the present. If generation time is 30 years, then all humans are 69th, or closer, cousins. For people with recent European ancestry, the MRSA time may be only half as long, about 1000 years.

The Probability of Pairwise Shared Ancestry and the Expected Number of Pairs of k-th Cousins in a Population Sample

An analytical solution is derived for the probability that a random pair of individuals from a panmictic population of size N will share ancestors who lived G generations previously. The analysis is extended to obtain 1) the probability that a sample of size s will contain at least one pair of (G - 1)th cousins;and 2) the expected number of pairs of (G - 1)th cousins in that sample. Solutions are given for both monogamous and promiscuous (non-monogamous) cases. Simulation results for a population size of N = 20,000 closely approximate the analytical expectations. Simulation results also agree very well with previously derived expectations for the proportion of unrelated individuals in a sample. The analysis is broadly consistent with genetic estimates of relatedness among a sample of 406 Danish school children, but suggests that a different genetic study of a heterogenous sample of Europeans overestimates the frequency of cousin pairs by as much as one order of magnitude.

New Evidence on the Common Ancestry of Tetrapods and Lungfish

As reported in a recent issue of Nature (Aug. 15, 2002),two Chinese scientists pinpoint their newly discovered fossil fish as the most direct piece of evi dence on the common ancestry shared by tetrapods (all land verte brates including human beings) and lungfish. This latest advance in studying the origin and evolution of early fishes was jointly made by Professor Zhu Min from the CAS Institute of Vertebrate Paleontology & Paleoanthropology and his colleague Yu Xiaobo, now a Professor at the Biology Department of Kean University (New Jersey, USA).……

Large-scale genome-wide SNP analysis reveals the rugged(and ragged)landscape of global ancestry,phylogeny,and demographic history in chicken breeds

The worldwide chicken gene pool encompasses a remarkable,but shrinking,number of divergently selected breeds of diverse origin.This study was a large-scale genome-wide analysis of the landscape of the complex molecular architecture,genetic variability,and detailed structure among 49 populations.These populations represent a significant sample of the world's chicken breeds from Europe(Russia,Czech Republic,France,Spain,UK,etc.),Asia(China),North America(USA),and Oceania(Australia).Based on the results of breed genotyping using the Illumina 60K single nucleotide polymorphism(SNP)chip,a bioinformatic analysis was carried out.This included the calculation of heterozygosity/homozygosity statistics,inbreeding coefficients,and effective population size.It also included assessment of linkage disequilibrium and construction of phylogenetic trees.Using multidimensional scaling,principal component analysis,and ADMIXTURE-assisted global ancestry analysis,we explored the genetic structure of populations and subpopulations in each breed.An overall 49-population phylogeny analysis was also performed,and a refined evolutionary model of chicken breed formation was proposed,which included egg,meat,dual-purpose types,and ambiguous breeds.Such a large-scale survey of genetic resources in poultry farming using modern genomic methods is of great interest both from the viewpoint of a general understanding of the genetics of the domestic chicken and for the further development of genomic technologies and approaches in poultry breeding.In general,whole genome SNP genotyping of promising chicken breeds from the worldwide gene pool will promote the further development of modern genomic science as applied to poultry.

Local ancestry and selection in admixed Sanjiang cattle

The majority of native cattle are taurine×indicine cattle of diverse phenotypes in the central region of China.Sanjiang cattle,a typical breed in the central region,play a central role in human livelihood and have good adaptability,including resistance to dampness,heat,roughage,and disease,and are thus regarded as an important genetic resource.However,the genetic history of the successful breed remains unknown.Here,we sequenced 10 Sanjiang cattle genomes and compared them to the 70 genomes of 5 representative populations worldwide.We characterized the genomic diversity and breed formation process of Sanjiang cattle and found that Sanjiang cattle have a mixed ancestry of indicine(55.6%)and taurine(33.2%)dating to approximately 30 generations ago,which has shaped the genome of Sanjiang cattle.Through ancestral fragment inference,selective sweep and transcriptomic analysis,we identified several genes linked to lipid metabolism,immune regulation,and stress reactions across the mosaic genome of Sanjiang cattle showing an excess of taurine or indicine ancestry.Taurine ancestry might contribute to meat quality,and indicine ancestry is more conducive to adaptation to hot climate conditions,making Sanjiang cattle a valuable genetic resource for the central region of China.Our results will help us understand the evolutionary history and ancestry components of Sanjiang cattle,which will provide a reference for resource conservation and selective breeding of Chinese native cattle.

AncestryPainter:A Graphic Program for Displaying Ancestry Composition of Populations and Individuals

Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used for ancestry inference increases remarkably, say more than 100 populations or 1000 individuals, it is usually challenging to present the ancestry composition in a traditional way using a rectangular graph. To address this issue, we developed a program,AncestryPainter, which can illustrate the ancestry composition of populations and individuals with a rounded and nice-looking graph to save space. Individuals are depicted as length-fixed bars partitioned into colored segments representing different ancestries, and the population of interest can be highlighted as a pie chart in the center of the circle plot. In addition, AncestryPainter can also be applied to display personal ancestry in a way similar to that for displaying population ancestry.AncestryPainter is publicly available at http://www.picb.ac.cn/PGG/resource.php.

Twenty-seven continental ancestry-informative SNP analysis of bone remains to resolve a forensic case

We employed our previously developed 27-plex ancestry-informative single nucleotide polymorphism(SNP)panel to infer the ancestral components of bone remains of a possible foreign pilot found in south-western China.For ancestry assignment of this unknown individual,we first obtained the 27-SNP genotype of the individual.Then,based on a reference database of 3081 individuals from 33 populations,we calculated the match probability and likelihood ratio using the self-developed software program Forensic Intelligence.Inferred ancestral components of this individual were calculated by structure at K=3.A complete profile was obtained for the individual using our multiplexed SNP assay.The European population was within one order of magnitude of the highest likelihood.The major ancestral component of this individual was 97.6%European.

Evaluation of ancestry from human skeletal remains: a concise review

Ancestry assessment represents a major component of forensic anthropological analysis of recovered human remains.Interpretations of ancestry,together with other aspects of the biological profile,can help narrow the search of missing persons and contribute to eventual positive identification.Such information can prove useful to authorities involved in the identification and investigative process since many lists of missing persons have a reference to this parameter.Recent research has strengthened available methodologies involving metric,non-metric morphological as well as chemical and genetic approaches.This review addresses the new anthropological techniques that are now available,as well as the complex historical context related to ancestry evaluation.

Purkait’s triangle revisited:role in sex and ancestry estimation

Identification of unknown remains recovered from marine and terrestrial locations is a significant humanitarian problem.This investigation proposes a simple method applicable to fragmentary femora for a more refined level of ancestry and/or sex estimation.To that end,we re-examined Purkait’s triangle which involves three inter-landmark distances between the traction epiphyses and the articular rim of femoral head.A large sample(n=584)from geographically diverse(Egyptian,Indian and Greek)populations was compiled.Additionally,shape(n=3)and trigonometrically derived variables and ratios(n=9 variables)were employed to detect any geographically-clustered morphological differences between these populations.Random forest modelling(RFM)and linear discriminant function analysis(LDA)were employed to create classification models in instances where sex was known or unknown.The sample was apportioned into training and test sets with a ratio 70/30.The classification accuracies were evaluated by means of k fold cross-validation procedure.In sex estimation,RFM showed similar performance to LDA.However,RFM outperformed LDA in ancestry estimation.Ancestry estimation was satisfactory in the Indian and Egyptian samples albeit the Greek sample was problematic.The Greek samples presented greater morphological overlap with the Indian sample due to high within-group variation.Test samples were accurately assigned to their ancestral category when sex was known.Generally,higher classification accuracies in the validation sample were obtained in the sex-specific model of females than in males.Using RFM and the linear variables,the overall accuracy reached 83%which is distributed as 95%,71%and 86%for the Egyptian,Indian and Greek females,respectively;whereas in males,the overall accuracy is 72%and is distributed as 58%,87%and 50%for the Egyptian,Indian and Greek males,respectively.Classification accuracies were also calculated per group in the test data using the 12 derived variables.For the females,the accuracies using the medians model was comparable to the linear model whereas in males the angles model outperformed the linear model for each group but with similar overall accuracy.The classification rates of male specific ancestry were 82%,78%and 56%for the Egyptian,Indian and Greek males,respectively.In conclusion,Purkait’s triangle has potential utility in ancestry and sex estimation albeit it is not possible to separate all groups successfully with the same efficiency.Intrapopulation variation may impact the accuracy of assigned group membership in forensic contexts.

Models, methods and tools for ancestry inference and admixture analysis

Background： Genetic admixture refers to the process or consequence of interbreeding between two or more previously isolated populations within a species. Compared to many other evolutionary driving forces such as mutations, genetic drift, and natural selection, genetic admixture is a quick mechanism for shaping population genomie diversity. In particular, admixture results in ＂recombination＂ of genetic variants that have been fixed in different populations, which has many evolutionary and medical implications. Results： However, it is challenging to accurately reconstruct population admixture history and to understand of population admixture dynamics. In this review, we provide an overview of models, methods, and tools for ancestry inference and admixture analysis. Conclusions： Many methods and tools used for admixture analysis were originally developed to analyze human data, but these methods can also be directly applied and/or slightly modified to study non-human species as well.

Use of Intraoral Three-dimensional Images for the Identification of Dental Morphological Traits Related to Ancestry Estimation

Victim identification through dental features is one of the main objectives of forensic dentistry.In circumstances where information regarding antemortem dental records is missing,reconstruction of a biological profile can be useful as a first step toward personal identification.This reconstructive method provides valuable information,namely regarding the individual’s ancestry,through the detection and degree of expression of dental morphological traits,which may help to restrict the number of candidates for identification.Technological advances allowed the development of alternative methods for dental evaluation,that complement or substitute those already in use in clinical practice.Among these,intraoral three‑dimensional(3D)images are increasingly used in dentistry,as they have a high level of accuracy and are easy to obtain and store.However,a fundamental question regarding forensic dentistry is whether they allow recognition and analysis of dental morphological traits in detail,namely those related to ancestry.In this study,we evaluated 20 teeth morphological features using intraoral 3D imaging from 77 individuals from Northern Portugal.Our results showed that it was possible to identify and classify a large part of the main morphological traits used in the estimation of ancestry.As these 3D images present sufficient morphological detail to be classified,we believe that future applications of this technique can be expected in forensic dentistry.

The Consistencies of Y‑Chromosomal and Autosomal Continental Ancestry Varying among Haplogroups

The Y‑chromosome has been widely used in ancestry inference based on its region‑specific haplogroup distributions.However,there is always a debate on how informative such a single marker is for inferring an individual’s genetic ancestry.Here,we compared genetic ancestry inferences at continental level made by Y‑chromosomal haplogroups to those made by autosomal single‑nucleotide polymorphisms in 1230 samples of Affymetrix Human Origins dataset.The highest ancestry proportions of a majority of individuals match the highest average continental‑ancestry proportions in haplogroups A,B,D,H,I,K,L,T,O,and M.The high consistencies have not been observed in haplogroups E,C,G,J,N,Q,and R,but in some of their sublineages,such as E1a,E1b1a1,E1b1b1b1a,E2b1a,J1a2b,Q1a1a1,Q1a2a1a1,R1b1a2a1a,and R2.Although the consistencies of Y‑chromosomal and autosomal continental ancestry vary among haplogroups,Y‑chromosome could provide valuable clues for individual’s continental ancestry.

Racial differences in the anatomical distribution of colorectal cancer:a study of differences between American and Chinese patients

AIM: To compare the racial differences of anatomical distribution of colorectal cancer (CRC) and determine the association of age, gender and time with anatomical distribution between patients from America (white) and China (oriental).METHODS: Data was collected from 690 consecutive patients in Cleveland Clinic Florida, U.S.A. and 870consecutive patients in Nan Fang Hospital affiliated to the First Military Medical University, China over the past 11years from 1990 to 2000. All patients had colorectal adenocarcinoma diagnosed by histology and underwent surgery.RESULTS: The anatomical subsite distribution of tumor,age and gender were significantly different between white and oriental patients. Lesions in the proximal colon (P＜0.001) were found in 36.3 % of white vs 26.0 % of oriental patients and cancers located in the distal colon and rectum in 63.7 % of white and 74 % of oriental patients (P＜0.001). There was a trend towards the redistribution from distal colon and rectum to proximal colon in white males over time, especially in older patients (＞80 years).No significant change of anatomical distribution occurred in white women and Oriental patients. The mean age at diagnosis was 69.0 years in white patients and 48.3 years in Oriental patients (P＜0.001).CONCLUSION: This is the first study comparing the anatomical distribution of colorectal cancers in whites and Chinese patients. White Americans have a higher risk of proximal CRC and this risk increased with time. The proportion of white males with CRC also increased with time.Chinese patients were more likely to have distal CRC and developed the disease at a significantly earlier age than white patients. These findings have enhanced our understanding of the disease process of colorectal cancer in these two races.

A Comparison between the Chinese and European Patients in Acupuncture Treatment

Based on my teaching and working experience in Europe, I have made a comparison between the Chinese and European patients in acupuncture treatment, and hope it is of some significance in acupuncture clinical practice.

Impact of type 2 diabetes on adenoma detection in screening colonoscopies performed in disparate populations

BACKGROUND The Black/African Ancestry(AA)population has a higher prevalence of type 2 diabetes mellitus(T2DM)and a higher incidence and mortality rate for colorectal cancer(CRC)than all other races in the United States.T2DM has been shown to increase adenoma risk in predominantly white/European ancestry(EA)populations,but the effect of T2DM on adenoma risk in Black/AA individuals is less clear.We hypothesize that T2DM has a significant effect on adenoma risk in a predominantly Black/AA population.AIM To investigate the effect of T2DM and race on the adenoma detection rate(ADR)in screening colonoscopies in two disparate populations.METHODS A retrospective cohort study was conducted on ADR during index screening colonoscopies(age 45-75)performed at an urban public hospital serving a predominantly Black/AA population(92%)(2017-2018,n=1606).Clinical metadata collected included basic demographics,insurance,body mass index(BMI),family history of CRC,smoking,diabetes diagnosis,and aspirin use.This dataset was combined with a recently reported parallel retrospective cohort data set collected at a suburban university hospital serving a predominantly White/EA population(87%)(2012-2015,n=2882).RESULTS The ADR was higher in T2DM patients than in patients without T2DM or prediabetes(35.2%vs 27.9%,P=0.0166,n=981)at the urban public hospital.Multivariable analysis of the combined datasets showed that T2DM[odds ratio(OR)=1.29,95%confidence interval(CI):1.08-1.55,P=0.0049],smoking(current vs never OR=1.47,95%CI:1.18-1.82,current vs past OR=1.32,95%CI:1.02-1.70,P=0.0026),older age(OR=1.05 per year,95%CI:1.04-1.06,P<0.0001),higher BMI(OR=1.02 per unit,95%CI:1.01-1.03,P=0.0003),and male sex(OR=1.87,95%CI:1.62-2.15,P<0.0001)were associated with increased ADR in the combined datasets,but race,aspirin use and insurance were not.CONCLUSION T2DM,but not race,is significantly associated with increased ADR on index screening colonoscopy while controlling for other factors.

Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels

Aim： To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. Methods： The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific anitgen （PSA） levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. Results： The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% （6/90） in our patients （P 〈 0.05）. The increased cancer detection rates decreased significantly when the patient PSA level increased from 0-20 ng/mL to 20.1-50 ng/mL and 〉 50 ng/mL （P 〈 0.01）. The number of positive biopsy cores in prostate cancer patients increased significantly with increasing patient PSA level （P 〈 0.01）. The rate of organ-confined prostate cancer decreased significantly with increasing patient PSA level （P 〈 0.01）. Conclusion： The extended 10- core strategy is recommended for Chinese patients with PSA 〈 20 ng/mL and the sextant strategy is recommended for those with PSA〉 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy 〉 10 years and the sextant strategy should be applied in those with life expectancy 〈 10 years. （Asian J Androl 2008 Mar; 10： 325-331）