Journal articles on the topic 'Ancestry'
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Illanes, Gabriel, María Inés Fariello, Lucía Spangenberg, Ernesto Mordecki, and Hugo Naya. "Testing the existence of an unadmixed ancestor from a specific population t generations ago." PLOS ONE 17, no. 8 (August 12, 2022): e0271097. http://dx.doi.org/10.1371/journal.pone.0271097.
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The ancestry of each locus of the genome can be estimated (local ancestry) based on sequencing or genotyping information together with reference panels of ancestral source populations. The length of those ancestry-specific genomic segments are commonly used to understand migration waves and admixture events. In short time scales, it is often of interest to determine the existence of the most recent unadmixed ancestor from a specific population t generations ago. We built a hypothesis test to determine if an individual has an ancestor belonging to a target ancestral population t generations ago based on these lengths of the ancestry-specific segments at an individual level. We applied this test on a data set that includes 20 Uruguayan admixed individuals to estimate for each one how many generations ago the most recent indigenous ancestor lived. As this method tests each individual separately, it is particularly suited to small sample sizes, such as our study or ancient genome samples.
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Oravcová, M. "Pedigree analysis in White Shorthaired goat: First results." Archives Animal Breeding 56, no. 1 (October 10, 2013): 547–54. http://dx.doi.org/10.7482/0003-9438-56-053.
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Abstract. Pedigree records of 1 682 animals of the White Shorthaired goat in Slovakia were investigated. The reference population was defined as the animals born from 2008 to 2011 with at least one ancestor known in the second ancestral generation (670 animals kept in eight flocks). The numbers of founders (286), ancestors (256), effective founders (73), effective ancestors (45) and founder genome equivalents (32) were assessed. Fifteen ancestors were needed to explain 50 % of genetic variability. Marginal contributions of the ten most influential ancestors varied between 5.45 % and 2.47 % and accounted for 39.8 % of genetic variability. The mean values of inbreeding and co-ancestry were 0.69 % and 1.55 %, respectively. The effective population size was assessed to consist of 182 and 142 individuals, depending whether it was calculated from the individual increase in inbreeding or the individual increase in co-ancestry. The number of maximum generations traced, fully traced generations and equivalent complete generations traced were 5.62, 1.97 and 3.04, respectively. The first, second and third ancestral generation were 100 %, 83 % and 71 % complete, respectively. The completeness decreased to as low as 35 % and 11 % in the fourth and fifth generation. To be able to keep genetic links across generations in touch, the amount of pedigree information needs to be increased. This is a serious requirement for appropriate monitoring and management of genetic relations within the population.
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Davy, Barbara Jane. "Inclusive Heathens Practice Ancestor Veneration, But Not Pride in Ancestry." Nova Religio 26, no. 3 (February 1, 2023): 30–51. http://dx.doi.org/10.1525/nr.2023.26.3.30.
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Ancestor veneration need not entail a focus on biological ancestry, but inclusive Heathens are troubled that white supremacists are attracted to Heathenry because of a perceived connection between ancestor veneration and pride in ancestry. The Canadian Heathens of Raven’s Knoll identify themselves as inclusive, and endeavor to exclude racists from their groups and events. Previous research has often distinguished between folkish (often racist) versus universalist (not racist) practitioners of Heathenry or Ásatrú. Inclusive Heathens welcome people of all backgrounds so long as they do not discriminate against others on the basis of spurious categories such as race, gender, or sexual orientation. Inclusive Heathens venerate a variety of ancestors, not just ancestors of blood or biological ancestors, but also ancestors of affinity or imagination, and ancestors of place. This contributes to a sense of relatedness and moral community beyond the intrahuman, and the development of ecological conscience at Raven’s Knoll.
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de Bonis, Louis, and George D. Koufos. "Our ancestors' ancestor: Ouranopithecus is a greek link in human ancestry." Evolutionary Anthropology: Issues, News, and Reviews 3, no. 3 (June 2, 2005): 75–83. http://dx.doi.org/10.1002/evan.1360030303.
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Lambert, Ronald D. "Reclaiming the ancestral past: narrative, rhetoric and the ‘convict stain’." Journal of Sociology 38, no. 2 (June 2002): 111–27. http://dx.doi.org/10.1177/144078302128756534.
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This paper reports the arguments used by members of two convictdescendant societies in embracing their convict ancestry. The data are taken from interviews that I conducted in 1999. In the main, respondents were involved in genealogy prior to discovering their or their spouses' convict ancestry. Respondents effectively countered ancestral stigma by making two kinds of argument. In the first, they recast ancestral convicts as: objects of quasi-professional interest; nation-builders; a minority within a multicultural society; collectibles; and embodying ‘interesting stories’. The second type of argument forwarded more particularized treatments of convict ancestors by: minimizing the gravity of their offences; temporally distancing descendants from them; empathizing with them; and claiming their redemption. I offer some concluding thoughts on the sociology of memory and the place of genealogical memory workers within the family.
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Campbell, R. B. "The Ancestry of Genetic Segments." ISRN Biomathematics 2012 (March 14, 2012): 1–8. http://dx.doi.org/10.5402/2012/384275.
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Recombination within a DNA segment during the neutral fixation process is studied to determine the number of individuals in previous generations which carry genetic material ancestral to that region in the present generation. If , where is the population size and is the probability of a recombination event within that region per individual in a generation, the ancestors of all the base pairs in that segment were probably in the same individual in an arbitrary generation in the asymptotic past (prior to the most recent common ancestor) and all the base pairs in that segment share a common coalescent. If , the ancestors of the base pairs in a segment are probably spread among several individuals in asymptotic generations; hence, there is not an ancestral individual, but an ancestral pool, and the coalescents of base pairs do not coincide. The overlap of the ancestral pools of unlinked genetic segments is less than where and are the relative frequencies of the two ancestral pools, which provides that the size of the ancestral pool for the human genome is close to the .80 upper bound which ensues from the Poisson progeny distribution.
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Garrison, Nanibaa' A. "Genetic Ancestry Testing with Tribes: Ethics, Identity & Health Implications." Daedalus 147, no. 2 (March 2018): 60–69. http://dx.doi.org/10.1162/daed_a_00490.
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Genetic ancestry tests have gained in popularity across the United States as more Americans seek answers about their ancestral past. The tests have been used to verify or dispute family stories about ancestors or to allow people to seek a sense of belonging with a particular tribe or community. They can also be useful in medical research to identify genetic variants across populations. At the same time, assumptions about genetic testing – and the very idea of a “genetic” identity – pose challenges for communities that are defined in terms of political, social, and cultural identities. This essay explores a range of uses of ancestry tests and their potential implications for Native American tribes and communities. It concludes that the scientific and recreational use of genetic ancestry testing continues to increase over time, but limitations of the consistency of results across platforms and the generalizability of knowledge remain.
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Don, Janith, Sara A. Byron, Guangfa Zhang, Tyler Izatt, Jiaming Zhang, Bethany Davis, Bryce Turner, et al. "Abstract A006: Increased germline mutational burden in individuals of African ancestry: Implications for interpretation of tumor mutation burden." Cancer Epidemiology, Biomarkers & Prevention 32, no. 1_Supplement (January 1, 2023): A006. http://dx.doi.org/10.1158/1538-7755.disp22-a006.
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Abstract Introduction: Tumor mutation burden (TMB), defined as the number of somatic gene mutations per megabase in a tumor genome, is used clinically to identify cancer patients that may respond to immune checkpoint inhibitors. Recent studies suggest that patient ancestry can influence TMB, where individuals of African ancestry were found to have elevated TMB values based on tumor-only sequencing analysis. However, the impact of patient ancestry on germline mutational burden and implications for interpretation of tumor-only mutational burden data is largely unexplored. Methods: We examined the influence of patient ancestry on germline and tumor mutation burden using tumor-normal whole exome sequencing (WES) data from a pan-cancer cohort of 1228 individuals from a single institution. Genetic ancestry was estimated from constitutional WES data using single nucleotide polymorphism weights from external reference panels. Variant calling was performed using constitutional, tumor-only, and paired tumor-normal workflows. Total and loss-of-function burden scores were calculated for each participant from each workflow based on the total number of mutations detected in each sample and the total number of predicted loss-of-function mutations, based on snpEff annotations, respectively. Results: Genetic ancestry analysis found that one-third of this pan-cancer cohort was of non-European ancestry. 9.4% of individuals were of Eastern Asian ancestry, 5.3% of African ancestry, 1.0% of South Asian ancestry, 0.2% of Native American ancestry, and 17.1% of admixed ancestry, predominantly European and Native American admixed ancestry (15.6%). Total and loss-of-function germline burden scores varied across ancestral groups, with individuals of African ancestry showing significantly increased germline burden scores compared to other ancestral groups (p<0.0001). Tumor-only analysis also showed increased mutation burden for individuals of African ancestry. However, when private and rare germline variation was taken into account using paired tumor-normal analysis, tumor mutation burden did not differ based on patient ancestry, suggesting the differences seen in tumor-only analysis are due to germline variation rather than differences in true somatic mutation burden. Conclusion: Our study reveals that the paucity of knowledge of ancestry-specific reference genomes leads to unacceptable health disparities in cancer, specifically in patients with African ancestry. We show that germline mutational burden varies by ancestral background, with individuals of African ancestry displaying increased genetic variation compared to other ancestral populations. These results suggest that patient ancestry should be considered when interpreting tumor mutational burden values, particularly from tumor-only analysis. Approaches utilizing paired tumor-normal analysis or ancestry-specific reference genomes can aid in more accurate assessment of TMB, thereby avoiding futile treatments targeted at presumed high mutational burden tumors specifically in African American populations. Citation Format: Janith Don, Sara A. Byron, Guangfa Zhang, Tyler Izatt, Jiaming Zhang, Bethany Davis, Bryce Turner, Jonathan J. Keats, Jeffrey M. Trent, Lorna Rodriguez-Rodriguez, Nicholas J. Schork. Increased germline mutational burden in individuals of African ancestry: Implications for interpretation of tumor mutation burden [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A006.
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Lee, Michelle Jeung-Eun, Manan Shah, Sri Lakshmi Sudha Kollepara, and Sanjay R. Jain. "Role of genetic ancestry in endometrial cancers: Understanding disparities in black women." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e17631-e17631. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e17631.
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e17631 Background: Endometrial cancer is the most common gynecological malignancy in the United States. Endometrial cancer disproportionately affects black women in terms of incidence and survival despite advancement in treatment, and preventive strategies. Identifying distinct tumor markers in patients with African ancestry will help distinguish biological determinants underlying the disparities in endometrial cancer. In this study, we investigated the genetic alterations in endometrial cancer in individuals of African (AFR) ancestry using The Cancer Genome Atlas (TCGA). Methods: The genomic and clinical data of TCGA PanCancer Atlas uterine corpus endometrial carcinoma (UCEC) were explored using CBioportal (http://www.cbioportal.org/). We utilized The Cancer Genome Ancestry Atlas (TCGAA) and LAMP for estimates of genetic ancestry and quantitative ancestral composition. This dataset contains 529 patients, including 357 self-reported whites and 107 blacks. For each case the proportion of European, West African, East Asian, Native American ancestry was estimated. The dominant ancestry was defined as ≥50% of admixture from one reference population. Differences in gene mutation frequency were analyzed based on AFR ancestry proportion. The Kaplan-Meier curves were generated, and Cox regression analyses were performed. Results: Global genetic ancestry analysis identified 115 AFR ancestry cases with mean ancestry of 80.4%. The dominant AFR ancestry subject matched the self-reported race with 94% accuracy. We identified 23 subjects with ≥90% AFR ancestry, 43 subjects with 80-90% AFR ancestry, 34 subjects with 70-80% AFR ancestry, and 15 subjects with 50-70% AFR ancestry. TP53 was the most frequently mutated gene in patients with AFR ancestry(49.5%). ≥90% AFR ancestry had the highest rate of TP53 mutations (52.2%) compared with 80-90% AFR ancestry (51.2%), 70-80% AFR ancestry (43.8%), and 50-70% AFR ancestry (41.7%). PTEN was less commonly mutated in patients with higher proportion of AFR ancestry (47.8% in ≥90% AFR ancestry, 39.0% in 80-90% AFR ancestry, 59.4% in 70-80% AFR ancestry, and 66.7% in 50-70% AFR ancestry). PIK3CA mutation frequency was almost identical in all AFR ancestry groups studied. No significant differences in overall survival was observed between AFR ancestry groups. Conclusions: We aimed to investigate the etiology of endometrial cancer disparities by analyzing the effect of ancestry on genetic alterations in endometrial cancer. This study demonstrated differences in the mutation frequency among patients with AFR ancestry. We have shown that TP53 mutations were seen more frequently in patients with higher AFR ancestry, which may confer a poorer prognosis. Nonetheless, to validate the findings of this study, future studies should be conducted with larger sample sizes and more diverse ancestral groups to explore how genetic ancestry impacts tumorigenesis and cancer progression.
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Choi, David, Michelle Jeung-Eun Lee, and Sanjay R. Jain. "Influence of ancestry in racial disparities of squamous cell lung cancer." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e20554-e20554. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e20554.
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e20554 Background: Significant progress has been made in the screening, diagnosis, and treatment of squamous cell carcinomas of the lung (LUSC). Despite the advancements, African American populations continue to experience worse disease burden and poorer overall survival, even after controlling for patient and tumor characteristics. While the interplay of various social determinants of health is well known to contribute to racial disparities in cancers, the molecular basis of racial disparity is less understood. Given the diversity of the US population that comprise of genetically admixed groups, understanding the role of ancestry and its influence on biology of cancers that drive incidence and prognosis is paramount to reducing racial disparities. Therefore, in this study, we aimed to investigate the influence of African (AFR) ancestry in genetic mutations of LUSC. Methods: We utilized The Cancer Genome Ancestry Atlas (TCGAA) to obtain data on the genetic ancestry and ancestral composition of 504 LUSC patients. The dataset contained 459 self-reported whites, 32 blacks, and 11 Asians. The percentage of each patient’s ancestral composition (European, AFR, Asian, and Native American) was revealed via the LAMP technique. The dominant ancestry was defined as those with genetic composition of ≥50% from one of four ancestral backgrounds. Genetic alteration profiles and clinical data of patients were obtained from LUSC TCGA PanCancer Atlas through GDC data portal. Of those with AFR dominant ancestry, we analyzed the differences in the gene mutation frequency based upon the proportion of AFR ancestry. Results: Ancestry analysis uncovered 30 AFR ancestry dominant cases with a mean AFR composition of 78.4%. We found 14 subjects with > 80% AFR ancestry and 16 subjects with 50-80% AFR ancestry. Two patients from the > 80% were excluded from the mutational analyses due to absence of genetic profiles in the data portal. TP53 was the most frequently mutated gene with a rate of 91.7% and 87.5% in > 80% and 50-80% AFR groups, respectively. Evaluation of the classic genetic mutations that drive disease pathology in LUSC (EGFR, ALK, PIK3CA, NRAS, KRAS) revealed 25% of > 80% AFR ancestry subjects carried mutations in at least one of these genes compared to 6.3% in the 50-80% AFR ancestry subjects. Also, a trend towards worse overall survival (OS) was seen in those with greater proportion of AFR ancestry (median OS of 27.2 months in > 80% group vs 43.9 months in 50-80% group). Conclusions: Despite the limited sample size, our study highlights substantial heterogeneity in tumor biology even within those of AFR ancestry and that genetic ancestry may impact tumor and host biology that contribute to disparities. Moving forward, engagement of the African American community into clinical trials and genomic studies are needed to explore ancestral influence on tumorigenesis, and to facilitate discovery of new actionable targets to help eradicate racial disparities in lung cancer.
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Choi, David, Michelle Jeung-Eun Lee, and Sanjay R. Jain. "Influence of ancestry in racial disparities of squamous cell lung cancer." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e20554-e20554. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e20554.
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e20554 Background: Significant progress has been made in the screening, diagnosis, and treatment of squamous cell carcinomas of the lung (LUSC). Despite the advancements, African American populations continue to experience worse disease burden and poorer overall survival, even after controlling for patient and tumor characteristics. While the interplay of various social determinants of health is well known to contribute to racial disparities in cancers, the molecular basis of racial disparity is less understood. Given the diversity of the US population that comprise of genetically admixed groups, understanding the role of ancestry and its influence on biology of cancers that drive incidence and prognosis is paramount to reducing racial disparities. Therefore, in this study, we aimed to investigate the influence of African (AFR) ancestry in genetic mutations of LUSC. Methods: We utilized The Cancer Genome Ancestry Atlas (TCGAA) to obtain data on the genetic ancestry and ancestral composition of 504 LUSC patients. The dataset contained 459 self-reported whites, 32 blacks, and 11 Asians. The percentage of each patient’s ancestral composition (European, AFR, Asian, and Native American) was revealed via the LAMP technique. The dominant ancestry was defined as those with genetic composition of ≥50% from one of four ancestral backgrounds. Genetic alteration profiles and clinical data of patients were obtained from LUSC TCGA PanCancer Atlas through GDC data portal. Of those with AFR dominant ancestry, we analyzed the differences in the gene mutation frequency based upon the proportion of AFR ancestry. Results: Ancestry analysis uncovered 30 AFR ancestry dominant cases with a mean AFR composition of 78.4%. We found 14 subjects with > 80% AFR ancestry and 16 subjects with 50-80% AFR ancestry. Two patients from the > 80% were excluded from the mutational analyses due to absence of genetic profiles in the data portal. TP53 was the most frequently mutated gene with a rate of 91.7% and 87.5% in > 80% and 50-80% AFR groups, respectively. Evaluation of the classic genetic mutations that drive disease pathology in LUSC (EGFR, ALK, PIK3CA, NRAS, KRAS) revealed 25% of > 80% AFR ancestry subjects carried mutations in at least one of these genes compared to 6.3% in the 50-80% AFR ancestry subjects. Also, a trend towards worse overall survival (OS) was seen in those with greater proportion of AFR ancestry (median OS of 27.2 months in > 80% group vs 43.9 months in 50-80% group). Conclusions: Despite the limited sample size, our study highlights substantial heterogeneity in tumor biology even within those of AFR ancestry and that genetic ancestry may impact tumor and host biology that contribute to disparities. Moving forward, engagement of the African American community into clinical trials and genomic studies are needed to explore ancestral influence on tumorigenesis, and to facilitate discovery of new actionable targets to help eradicate racial disparities in lung cancer.
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Ma, Hongying, Sheng Wang, Guorong Zeng, Jintu Guo, Minghao Guo, Xianggui Dong, Guoying Hua, et al. "The Origin of a Coastal Indigenous Horse Breed in China Revealed by Genome-Wide SNP Data." Genes 10, no. 3 (March 21, 2019): 241. http://dx.doi.org/10.3390/genes10030241.
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: The Jinjiang horse is a unique Chinese indigenous horse breed distributed in the southern coastal areas, but the ancestry of Jinjiang horses is not well understood. Here, we used Equine SNP70 Bead Array technology to genotype 301 horses representing 10 Chinese indigenous horse breeds, and we integrated the published genotyped data of 352 individuals from 14 foreign horse breeds to study the relationships between Jinjiang horses and horse breeds from around the world. Principal component analysis (PCA), linkage disequilibrium (LD), runs of homozygosity (ROH) analysis, and ancestry estimating methods were conducted to study the population relationships and the ancestral sources and genetic structure of Jinjiang horses. The results showed that there is no close relationship between foreign horse breeds and Jinjiang horses, and Jinjiang horses shared a similar genetic background with Baise horses. TreeMix analysis revealed that there was gene flow from Chakouyi horses to Jinjiang horses. The ancestry analysis showed that Baise horses and Chakouyi horses are the most closely related ancestors of Jinjiang horses. In conclusion, our results showed that Jinjiang horses have a native origin and that Baise horses and Chakouyi horses were key ancestral sources of Jinjiang horses. The study also suggested that ancient trade activities and the migration of human beings had important effects on indigenous horse breeds in China.
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Chang, Joseph T. "Recent common ancestors of all present-day individuals." Advances in Applied Probability 31, no. 4 (December 1999): 1002–26. http://dx.doi.org/10.1239/aap/1029955256.
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Previous study of the time to a common ancestor of all present-day individuals has focused on models in which each individual has just one parent in the previous generation. For example, ‘mitochondrial Eve’ is the most recent common ancestor (MRCA) when ancestry is defined only through maternal lines. In the standard Wright-Fisher model with population size n, the expected number of generations to the MRCA is about 2n, and the standard deviation of this time is also of order n. Here we study a two-parent analog of the Wright-Fisher model that defines ancestry using both parents. In this model, if the population size n is large, the number of generations, 𝒯n, back to a MRCA has a distribution that is concentrated around lgn (where lg denotes base-2 logarithm), in the sense that the ratio 𝒯n(lgn) converges in probability to 1 as n→∞. Also, continuing to trace back further into the past, at about 1.77 lgn generations before the present, all partial ancestry of the current population ends, in the following sense: with high probability for large n, in each generation at least 1.77lgn generations before the present, all individuals who have any descendants among the present-day individuals are actually ancestors of all present-day individuals.
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Chang, Joseph T. "Recent common ancestors of all present-day individuals." Advances in Applied Probability 31, no. 04 (December 1999): 1002–26. http://dx.doi.org/10.1017/s0001867800009587.
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Previous study of the time to a common ancestor of all present-day individuals has focused on models in which each individual has just one parent in the previous generation. For example, ‘mitochondrial Eve’ is the most recent common ancestor (MRCA) when ancestry is defined only through maternal lines. In the standard Wright-Fisher model with population size n, the expected number of generations to the MRCA is about 2n, and the standard deviation of this time is also of order n. Here we study a two-parent analog of the Wright-Fisher model that defines ancestry using both parents. In this model, if the population size n is large, the number of generations, 𝒯 n , back to a MRCA has a distribution that is concentrated around lgn (where lg denotes base-2 logarithm), in the sense that the ratio 𝒯 n (lgn) converges in probability to 1 as n→∞. Also, continuing to trace back further into the past, at about 1.77 lgn generations before the present, all partial ancestry of the current population ends, in the following sense: with high probability for large n, in each generation at least 1.77lgn generations before the present, all individuals who have any descendants among the present-day individuals are actually ancestors of all present-day individuals.
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Mekhfi, Lamiaa, Bouchra El Khalfi, Rachid Saile, Hakima Yahia, and Abdelaziz Soukri. "The interest of informative ancestry markers (AIM) and their fields of application." BIO Web of Conferences 115 (2024): 07003. http://dx.doi.org/10.1051/bioconf/202411507003.
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This review focuses on the study of biogeographic ancestry using the Accurate Ancestry Identification Panel. Autosomal markers may provide little information about the nature of an individual's admixture due to ongoing human recombination and migration. Biogeographic ancestry assessment (BGA) is a term used to describe ancestry through DNA testing. This is usually accomplished by testing specific regions of DNA called ancestry information markers (AIMs). AIMs are chosen because they expose significantly different frequencies between different populations in different parts of the world. The panels of these AIMs can be assessed using next-generation sequencing (NGS) to predict the geographical origins of a person of interest's ancestors, usually in terms of continent of origin, and sometimes by smaller geographic regions. The use of ancestry informative markers (AIM) to identify genomic ancestry can be useful for a variety of studies in evolutionary genetics, biomedical research, and forensic analyses. However, there remains a major challenge in determining AIMs for populations with complex and highly mixed ancestry.
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Thomas, Valorie. "Ancestry." Frontiers: A Journal of Women Studies 14, no. 2 (1994): 121. http://dx.doi.org/10.2307/3346634.
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Smith, Leslie A., James A. Cahill, and Kiley Graim. "Abstract 1922: PhyloFrame: A machine learning framework for ancestry agnostic disease signatures." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1922. http://dx.doi.org/10.1158/1538-7445.am2023-1922.
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Abstract Rapid advancements in genomic sequencing technologies have catalyzed the molecular identification and treatment of previously elusive diseases. Despite these genomic advancements, disparities in precision medicine access and data have resulted in disparate impacts on different socioeconomic groups. Many of the gold standard datasets largely exclude minority populations, compounding their exclusion from medical research. This has resulted in a restricted understanding of cancer and other complex diseases. We demonstrate the effects of ancestral bias in gold standard genomics datasets through ancestral analysis of cancer-related genes in the Cancer Gene Census, spanning 17 ancestral populations. Additionally, we present a machine learning framework, PhyloFrame, that incorporates population genomics data to correct for ancestral bias by creating disease signatures representative of all ancestries. Our ancestral analysis results show that while a majority of the current cancer-related genes in the Cancer Gene Census have below average mutation frequency in non-European populations, there are peaks of ancestrally enriched mutations in ancestry-specific genes related to cancer, which can be targeted using PhyloFrame. PhyloFrame prioritizes gene expression from the cancer genes with high frequency mutations in a given human population in order to capture genes driving disease in each ancestry. It builds on existing disease gene signatures and big-data functional interaction networks to identify ancestry-relevant genes related to a disease, outputing an ancestry-agnostic disease signature. We test PhyloFrame on TCGA cancers with diverse patient populations, such as breast cancer, and compare PhyloFrame's disease signature output to the disease signature output of elastic net runs on cancer samples from a single ancestry. Our results demonstrate that the incorporation of ancestral information allows PhyloFrame to recapitulate disease signatures trained on only one ancestry in a dataset with individuals from many unquantified ancestries. With the incorporation of ancestral information, PhyloFrame is able to create disease signatures with genes pertinent to each ancestral population, even when individuals from those populations are not included in the training data. This work offers a quick and cheap alternative to the mass sequencing that would be required to capture disease-driving genes in minority populations in hopes to contribute to equitable representation in medical research. Citation Format: Leslie A. Smith, James A. Cahill, Kiley Graim. PhyloFrame: A machine learning framework for ancestry agnostic disease signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1922.
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Lee, Michelle Jeung-Eun, Eric Chang, Manan Shah, and Sanjay R. Jain. "Racial disparities in lung adenocarcinoma: The contribution of African ancestry." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 8516. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.8516.
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8516 Background: Racial disparities in lung cancer are well-known with African Americans disproportionally affected by lung cancer in terms of incidence and survival. Previous comparative analyses of molecular features of lung cancer revealed racial differences in genomic profiles, which supports somatic differences arising from genetic ancestry. Using The Cancer Genome Atlas (TCGA), we investigated the genetic alterations in lung adenocarcinomas (LUAD) on individuals of African (AFR) ancestry. Methods: The genomic and clinical data of TCGA PanCancer Atlas LUAD were downloaded through the GDC Data Portal. Given that substantial proportion of the US population consist of genetically admixed populations, we utilized The Cancer Genome Ancestry Atlas (TCGAA) and LAMP for estimates of genetic ancestry and quantitative ancestral compositions. This dataset contains 518 samples, including 393 self-reported whites and 52 African Americans. For each case the proportion of European, AFR, East Asian, native American ancestry was estimated. The dominant ancestry was defined as ≥50% of admixture from one reference population. Differences in gene mutation frequency were analyzed based on AFR ancestry proportion. The Kaplan-Meier curves were generated, and Cox regression analyses were performed. Results: Global ancestry analysis identified 50 AFR ancestry cases with mean ancestry of 78.3%. The dominant AFR ancestry group matched the self-reported race with 96% accuracy. We identified 9 subjects with ≥90% AFR ancestry, 22 subjects with 80-90% AFR ancestry, 12 subjects with 70-80% AFR ancestry, and 7 subjects with 50-70% AFR ancestry. TP53 was the most frequently mutated gene, and ≥90% AFR ancestry had the highest rate of mutations (77.8%) compared with 80-90% AFR ancestry (68.2%), and 70-80% AFR ancestry (66.8%). We evaluated classic driver gene mutations (EGFR, KRAS, NRAS, PIK3CA, ALK) and found only 33% of ≥90% AFR ancestry subjects carry a known driver mutation, compared to 58-77% in lower proportion of AFR ancestry subjects. Higher AFR ancestry was associated with worse overall survival (OS) and progression free survival (PFS). Median OS was 14.5 months for ≥90% AFR ancestry compared to 71.47 months in 70-80% AFR ancestry (P = 0.048). ≥90% AFR ancestry had median PFS of 12.8 months compared to 33.5 months in 80-90% AFR ancestry, and 47.1 months in 70-80% AFR ancestry (P = 0.002). Conclusions: This study demonstrates the power of genomic study to investigate the etiology of health disparities by analyzing the effect of ancestry on genetic alterations in LUAD. Our results reveal different mutation loads even among AFR ancestry patients. We observed that AFR ancestry is associated with worse OS, suggesting possible influence of germline ancestry in subsequent somatic alterations. Further work is needed to explore how genetic ancestry impacts tumorigenesis and cancer progression to eliminate lung cancer disparities.
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Wangkumhang, Pongsakorn, Alisa Wilantho, Philip J. Shaw, Laurence Flori, Katayoun Moazami-Goudarzi, Mathieu Gautier, Monchai Duangjinda, Anunchai Assawamakin, and Sissades Tongsima. "Genetic analysis of Thai cattle reveals a Southeast Asian indicine ancestry." PeerJ 3 (October 27, 2015): e1318. http://dx.doi.org/10.7717/peerj.1318.
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Cattle commonly raised in Thailand have characteristics ofBos indicus(zebu). We do not know when or how cattle domestication in Thailand occurred, and so questions remain regarding their origins and relationships to other breeds. We obtained genome-wide SNP genotypic data of 28 bovine individuals sampled from four regions: North (Kho-Khaolampoon), Northeast (Kho-Isaan), Central (Kho-Lan) and South (Kho-Chon) Thailand. These regional varieties have distinctive traits suggestive of breed-like genetic variations. From these data, we confirmed that all four Thai varieties areBos indicusand that they are distinct from other indicine breeds. Among these Thai cattle, a distinctive ancestry pattern is apparent, which is the purest within Kho-Chon individuals. This ancestral component is only present outside of Thailand among other indicine breeds in Southeast Asia. From this pattern, we conclude that a uniqueBos indicusancestor originated in Southeast Asia, and native Kho-Chon Thai cattle retain the signal of this ancestry with limited admixture of other bovine ancestors.
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KO, KICHUL, BEVERLY S. FRANEK, MIRANDA MARION, KENNETH M. KAUFMAN, CARL D. LANGEFELD, JOHN B. HARLEY, and TIMOTHY B. NIEWOLD. "Genetic Ancestry, Serum Interferon-α Activity, and Autoantibodies in Systemic Lupus Erythematosus." Journal of Rheumatology 39, no. 6 (April 15, 2012): 1238–40. http://dx.doi.org/10.3899/jrheum.111467.
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Objective.To investigate and refine the relationships among systemic lupus erythematosus (SLE) and related autoantibodies, interferon-α (IFN-α), and various ancestral backgrounds.Methods.We investigated quantitatively defined genetic ancestry through principal component analysis in place of self-reported ancestry.Results.African ancestry was found to be associated with presence of anti-RNP antibody (p = 0.0026), and anti-RNP was correlated with high levels of IFN-α (p = 2.8 × 10−5).Conclusion.Our data support a model in which African ancestry increases the likelihood of SLE-associated autoantibody formation, which subsequently results in higher levels of serum IFN-α.
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Aijmer, Göran. "Ancestors and Ancestry in Southwestern China. Transforms in Tradition." Anthropos 113, no. 2 (2018): 437–52. http://dx.doi.org/10.5771/0257-9774-2018-2-437.
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Loon, Erica, Cindy Narvaez-Barbecho, Jhon Prieto Ortiz, Domingo Balderramo, Enrique Carrera, Javier Dias-Ferrer, Marco Arrese, Angelo Z. Mattos, Andre Boonstra, and Jose Debes. "Association Between Hepatocellular Carcinoma Epidemiology and Self-Reported Ancestry in Latin America." JCO Global Oncology 10, Supplement_1 (July 2024): 22–23. http://dx.doi.org/10.1200/go-24-23000.
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PURPOSE Hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD, now MASLD) is a growing health concern worldwide particularly in areas of high endemicity such as Latin America. The region has a uniquely mixed population of high ancestral diversity which has been minimally studied. We aimed to assess the role of ancestry in HCC risk factors in Latin America. METHODS We retrospectively evaluated data from the ESCALON network, a European-Latin American network that prospectively follows patients with HCC to assess clinical, demographic, and ancestral parameters. A total of 429 individuals with HCC from 6 countries in Latin America were studied: Argentina (34% N: 145), Chile (15% N: 66), Ecuador (15% N: 63), Peru (15% N: 66), Colombia (14% N: 60), and Brazil (7% N: 29). Self-reported ancestry was categorized as European or Non-European which included the following: Amerindian or Indigenous, African, Asian, or other. HCC was diagnosed per standard AASLD guidelines. RESULTS 131 patients (30.5%) reported having European ancestry and 298 (69.5%) non-European ancestry. Median age in both cohorts was 68 years. 72% of patients in the European cohort were male compared to 62% in the non-European cohort. The most common etiology for HCC in the European cohort was hepatitis C virus (38%) compared to NAFLD (52%) in the non-European cohort. Alcohol use disorder was the second most common etiology in both groups (25% European, 23% Non-European). Both European and Non-European ancestry cohorts had a similar proportion of HCC diagnosed under surveillance (40% and 41%, respectively) and similar presence of extrahepatic disease (47% and 50%, respectively). Interestingly, self-reported ancestry was associated with differential proportions of certain genetic polymorphisms including STAT4 and MBOAT7, suggesting a correlation between self-reporting of ancestry and genetic expression. CONCLUSION NAFLD-HCC was more common in Latin American patients of non-European descent compared to those of European descent, suggesting that ancestry may contribute to underlying liver disease, and in turn, the risk for HCC. However, larger studies including admixture analyses are needed to better understand this interaction.
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Kudryavtseva, M. E. "Studying Genealogy as a Factor of Cultural Self-Identification of the Person." Discourse 6, no. 1 (March 5, 2020): 62–71. http://dx.doi.org/10.32603/2412-8562-2020-6-1-62-71.
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Introduction. The paper considers the problem of cultural identity influenced by the study of ancestry. The scientific novelty of this paper is due to the attention to the psychological aspects of self-identity under the influence of the study of person, her or his ancestry, and, above all, in a situation of detection of undesirable information about his or her family's past. It is hypothesized that motifs associated with the need to rethink its social role in terms of responsibility for the acts of their ancestors, do not play a significant role in the study of family history.Methodology and sources. The paper analyzes the results of the pilot Internet study conducted to determine the motives and methods of the study of person's ancestry, as well as the stability of interest in this activity. The target audience of this study were all who are interested in learning their ancestors, regardless of age or occupational category. The questionnaire used was semi-closed. A total of 154 people were interviewed.Results and discussion. The results showed that 46.8 % of respondents interest in their ancestry has a playful nature; 37.0 % desire through your family history to better understand the history of their country; 33.0 % of respondents are interested in their ancestry in order to better understand the reasons for their behavior (which is a necessary component of self identification); 32.0 % would like to find ancestors, who could be proud of. Nevertheless, in the case of unsolicited information about the life of their ancestors, are ready to make conclusions about his or her own life less than four percent of the respondents.Conclusion. The author believes that the paper put forward the hypothesis that motifs associated with the need to rethink its social role in terms of responsibility for the acts of their ancestors, do not play a significant role in the study of family history is confirmed by the results of the study. In case of detection of unwanted results, mainly protective mechanisms are becoming actual, ensuring the preservation of psychological comfort.
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Davis, Melissa, Rachel Martini, Lisa Newman, Olivier Elemento, Jason White, Akanksha Verma, Indrani Datta, et al. "Identification of Distinct Heterogenic Subtypes and Molecular Signatures Associated with African Ancestry in Triple Negative Breast Cancer Using Quantified Genetic Ancestry Models in Admixed Race Populations." Cancers 12, no. 5 (May 13, 2020): 1220. http://dx.doi.org/10.3390/cancers12051220.
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Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n = 42) and European American (EA, n = 33) women. RNA sequencing data were analyzed to measure changes in genome-wide expression, and we utilized logistic regressions to identify ancestry-associated gene expression signatures. Using SNVs identified from our RNA sequencing data, global ancestry was estimated. We identified 156 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like two tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.
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Dakroury, Youssra, Stephen L. Atkin, Soha R. Dargham, Amal Robay, Juan Rodriguez-Flores, Ronald G. Crystal, and Alexandra E. Butler. "Qatari Genotype May Contribute to Complications in Type 2 Diabetes." Journal of Diabetes Research 2020 (June 10, 2020): 1–6. http://dx.doi.org/10.1155/2020/6356973.
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Objective. There is increasing evidence of a strong genetic component in type 2 diabetes (T2DM) that may contribute to diabetes complications. Given the high prevalence of diabetes with its associated complications in the Middle East, we sought to determine if the genotype within a Middle East population may be contributory. Therefore, three genotype-based Qatari ancestral groups, Q1 Arab Bedouin, Q2 Asian/Persian, and Q3 sub-Saharan African, with a fourth admixed group were correlated with T2DM prevalence and its complications to determine if they differed between the 4 Qatari ancestries, particularly for the SLMAP allele-associated diabetic retinopathy. Methods. In this cross-sectional study, 398 Qatari subjects, 220 with and 178 without T2DM, were genotyped by Affymetrix 500k SNP arrays. Ancestry was correlated with diabetes complications. Results. 398 subjects were included, the mean age was 49.8 years, and 56.8% were male. The genotype-based ancestry and T2DM prevalence were as follows: 164 (41.2%) with ancestry Q1, 60.4% with T2DM; 149 (37.4%) with ancestry Q2, 49.7% with T2DM; 31 (7.8%) with ancestry Q3, 61.3% with T2DM; and 54 (13.6%) with “admixed” ancestry, 51.9% with T2DM. For patients with diabetes, hypertension (p<0.035) and retinopathy (p<0.016) were greater in the Q3 ancestry. Conclusion. These data suggest that the genotype may contribute to complication risk, as exemplified by the increase in hypertension and retinopathy in the Q3 ancestry, though the SLMAP allele was not implicated; however, diabetes prevalence did not differ between the four Qatari ancestries.
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Hahn, Robert A., Benedict I. Truman, and Nancy D. Barker. "Identifying Ancestry." Epidemiology 7, no. 1 (January 1996): 75–80. http://dx.doi.org/10.1097/00001648-199601000-00013.
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Bammesberger, A. "Grendel's Ancestry." Notes and Queries 55, no. 3 (July 1, 2008): 257–60. http://dx.doi.org/10.1093/notesj/gjn112.
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Song, Xi, Cameron D. Campbell, and James Z. Lee. "Ancestry Matters." American Sociological Review 80, no. 3 (April 21, 2015): 574–602. http://dx.doi.org/10.1177/0003122415576516.
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Harmon, Katherine. "Shattered Ancestry." Scientific American 308, no. 2 (January 14, 2013): 42–49. http://dx.doi.org/10.1038/scientificamerican0213-42.
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Tvedebrink, Torben, and Poul Svante Eriksen. "Inference of admixed ancestry with Ancestry Informative Markers." Forensic Science International: Genetics 42 (September 2019): 147–53. http://dx.doi.org/10.1016/j.fsigen.2019.06.013.
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Rouet, Romain, David B. Langley, Peter Schofield, Mary Christie, Brendan Roome, Benjamin T. Porebski, Ashley M. Buckle, et al. "Structural reconstruction of protein ancestry." Proceedings of the National Academy of Sciences 114, no. 15 (March 29, 2017): 3897–902. http://dx.doi.org/10.1073/pnas.1613477114.
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Ancestral protein reconstruction allows the resurrection and characterization of ancient proteins based on computational analyses of sequences of modern-day proteins. Unfortunately, many protein families are highly divergent and not suitable for sequence-based reconstruction approaches. This limitation is exemplified by the antigen receptors of jawed vertebrates (B- and T-cell receptors), heterodimers formed by pairs of Ig domains. These receptors are believed to have evolved from an extinct homodimeric ancestor through a process of gene duplication and diversification; however molecular evidence has so far remained elusive. Here, we use a structural approach and laboratory evolution to reconstruct such molecules and characterize their interaction with antigen. High-resolution crystal structures of reconstructed homodimeric receptors in complex with hen-egg white lysozyme demonstrate how nanomolar affinity binding of asymmetrical antigen is enabled through selective recruitment and structural plasticity within the receptor-binding site. Our results provide structural evidence in support of long-held theories concerning the evolution of antigen receptors, and provide a blueprint for the experimental reconstruction of protein ancestry in the absence of phylogenetic evidence.
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Jin, Xiao-Ye, Yu-Xin Guo, Chong Chen, Wei Cui, Yan-Fang Liu, Yun-Chun Tai, and Bo-Feng Zhu. "Ancestry Prediction Comparisons of Different AISNPs for Five Continental Populations and Population Structure Dissection of the Xinjiang Hui Group via a Self-Developed Panel." Genes 11, no. 5 (May 4, 2020): 505. http://dx.doi.org/10.3390/genes11050505.
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Ancestry informative markers are genetic markers that show distinct genetic divergences among different populations. These markers can be utilized to discern population substructures and estimate the ancestral origins of unknown individuals. Previously, we developed a multiplex system of 30 ancestry informative single nucleotide polymorphism (AISNP) loci to facilitate ancestral inferences in different continental populations. In the current study, we first compared the ancestry resolutions of the 30 AISNPs and the other previously reported AISNP panels for African, European, East Asian, South Asian and American populations. Next, the genetic components of the Xinjiang Hui group were further explored in comparison to these continental populations based on the 30 AISNPs. Genetic divergence analyses of the 30 AISNPs in these five continental populations revealed that most of the AISNPs showed high genetic differentiations between these populations. Ancestry analysis comparisons of the 30 AISNPs and other published AISNPs revealed that these 30 AISNPs had comparable efficiency to other AISNP panels. Genetic relationship analyses among the studied Hui group and other continental populations demonstrated that the Hui group had close genetic affinities with East Asian populations and might share the genetic ancestries with East Asian populations. Overall, the 30 AISNPs can be used to predict the bio-geographical origins of different continental populations. Moreover, the obtained genetic data of 30 AISNPs in the Hui group can further enrich the extant reference data, which can be used as reference data for ancestry analyses of the Hui group.
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Tusso, Sergio, Bart P. S. Nieuwenhuis, Fritz J. Sedlazeck, John W. Davey, Daniel C. Jeffares, and Jochen B. W. Wolf. "Ancestral Admixture Is the Main Determinant of Global Biodiversity in Fission Yeast." Molecular Biology and Evolution 36, no. 9 (May 20, 2019): 1975–89. http://dx.doi.org/10.1093/molbev/msz126.
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Abstract Mutation and recombination are key evolutionary processes governing phenotypic variation and reproductive isolation. We here demonstrate that biodiversity within all globally known strains of Schizosaccharomyces pombe arose through admixture between two divergent ancestral lineages. Initial hybridization was inferred to have occurred ∼20–60 sexual outcrossing generations ago consistent with recent, human-induced migration at the onset of intensified transcontinental trade. Species-wide heritable phenotypic variation was explained near-exclusively by strain-specific arrangements of alternating ancestry components with evidence for transgressive segregation. Reproductive compatibility between strains was likewise predicted by the degree of shared ancestry. To assess the genetic determinants of ancestry block distribution across the genome, we characterized the type, frequency, and position of structural genomic variation using nanopore and single-molecule real-time sequencing. Despite being associated with double-strand break initiation points, over 800 segregating structural variants exerted overall little influence on the introgression landscape or on reproductive compatibility between strains. In contrast, we found strong ancestry disequilibrium consistent with negative epistatic selection shaping genomic ancestry combinations during the course of hybridization. This study provides a detailed, experimentally tractable example that genomes of natural populations are mosaics reflecting different evolutionary histories. Exploiting genome-wide heterogeneity in the history of ancestral recombination and lineage-specific mutations sheds new light on the population history of S. pombe and highlights the importance of hybridization as a creative force in generating biodiversity.
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Coelho, Carlos M., Kullaya Pisitsungkagarn, Nattasuda Taephant, and Carey D. Balaban. "COMPARING DIZZINESS AND VERTIGO INVENTORY RESPONSES IN THAI AND THAI-CHINESE PEOPLE." Acta Neuropsychologica 17, no. 1 (February 12, 2019): 55–67. http://dx.doi.org/10.5604/01.3001.0013.1850.
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It is acknowledged that ancestry may play a role in the likelihood of reporting motion sickness, based upon questionnaires in which symptoms are reported more frequently in individuals with Asian ancestry. This study compares motion sickness and related vertigo syndromes in Thai and Thai-Chinese populations. The Motion Sickness Questionnaire; Albany Panic and Phobia Questionnaire; Acrophobia Questionnaire; Body Symptoms Questionnaire and the Situational Characteristics Questionnaire were administered to 128 participants. Eighty-eight participants had a father, mother and all grandparents of Thai origin, while 44 participants had with at least one Chinese ancestor among parents or grandparents. All responses were similar between groups except regarding fear of heights, which is significantly higher in Thai participants without recent Chinese ancestors. Reported motion sickness sensitivity is similar between Thai and Chinese populations. The group differences for some fear of heights items may be linked to each group’ previous experience with heights. Results also suggest that although conquering a fear of heights might require specific visuo-vestibular adaptations, these adaptations alone may not be sufficient to lessen an individual’sfear of heights.
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Hughes, Elisha, Placede Tiemeny, Shannon Gallagher, Stephanie Meek, Charis Eng, Monique Gary, Ora Gordon, et al. "Ancestrally unbiased polygenic breast cancer (BC) risk assessment." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10502. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10502.
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10502 Background: BC risk is influenced by single-nucleotide polymorphisms (SNPs) with small effects that can be aggregated into polygenic risk scores (PRSs). PRSs have primarily been developed and validated for populations of European descent. To make a PRS available for all women, we developed and validated a novel global PRS (gPRS) that utilizes individual ancestral genetic composition. Methods: Ancestry-specific PRSs corresponding to 3 continental ancestries were developed from 149 SNPs (93 BC and 56 ancestry-informative): an African PRS was developed using a cohort of 31,126 self-reported African American patients referred for hereditary cancer testing; an East Asian PRS was developed based on published data from the Asia Breast Cancer Consortium; and a European PRS was developed using data from the Breast Cancer Association Consortium and 24,259 European hereditary cancer testing patients. For each patient, ancestry-informative SNPs were used to calculate the fractional ancestry attributable to each of the 3 continents. The gPRS was the sum of ancestry specific PRSs weighted according to genetic ancestral composition. In an independent validation cohort (N = 62,707), we evaluated discrimination and calibration of gPRS, and compared performance against a previously described 86-SNP PRS for women of European ancestry. Associations of SNPs and PRSs with BC were analyzed using logistic regression adjusted for personal and family cancer history, age, and ancestry. Odds ratios (ORs) are reported per standard deviation within the corresponding patient population. P-values are reported as two-sided. Results: The gPRS was strongly associated with BC in the full validation cohort and in sub-cohorts defined by self-reported ancestry (Table). 95% (88/93) of BC SNPs had ≥1% frequency of risk alleles within each of the self-reported populations. Compared to the aforementioned 86-SNP PRS, the gPRS showed improved discrimination overall, and within each sub-cohort, with the exception of the Asian population where the sample size was too small to show superiority of either score. The 86-SNP PRS was calibrated for white non-Hispanic women but mis-calibrated for non-European ancestries. The gPRS was properly calibrated for all women. Conclusions: The 149-SNP gPRS is validated and calibrated for women of all ancestries. Combined with clinical and biological risk factors, this approach may offer improved risk stratification for all women, regardless of ancestry.[Table: see text]
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Nassar, Amin, Elio Adib, Sarah Abou Alaiwi, Elie Akl, Talal El Zarif, Pier Vitale Nuzzo, Tarek H. Mouhieddine, et al. "Genetic ancestry and clinical outcomes to immune checkpoint inhibitors among seven common cancers." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10536. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10536.
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10536 Background: Prior studies and clinical trials report associations between self-reported race and clinical outcomes to Immune Checkpoint Inhibitors (ICIs). However, comprehensive studies of ancestry-associated differences in clinical outcomes have not been performed. We derived genetic ancestry scores and assessed clinical outcomes in 1341 patients with cancer treated with ICIs. Methods: Patients at the Dana-Farber Cancer Institute treated with ICIs only and with relevant cancer types and targeted exome sequencing data (Oncopanel) were included. Relevant cancer types included colorectal adenocarcinoma (CRC), esophagogastric adenocarcinoma (EGC), head and neck squamous cell carcinoma (HNSCC), melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and urothelial carcinoma (UC). We developed a bioinformatics pipeline to infer fine-scale genetic ancestry for each patient (n=1341) directly from tumor sequencing data by leveraging off and on-target sequenced reads and external ancestry reference panels. Three ancestry scores were determined (African, East Asian, European). Overall survival (OS) and time-to-treatment failure (TTF) were compared by Cox logistic regression between ancestral populations. Hazard ratio (HR) was derived using multivariable analysis, adjusted for single versus combination therapy, prior lines of therapy, and tumor mutational burden (TMB, as percentiles). Results: Median follow-up was 37.8 months (m; interquartile range: 35.7-39.5m). Common cancer types included CRC (n=52), EGC (n=114), HNSCC (n=88), melanoma (n=274), NSCLC (n=571), RCC (n=99), and UC (n=143). A higher East Asian ancestry (EAS) was significantly associated with worse OS ( p=0.03) and TTF ( p=0.002) in patients with RCC, independent of the histologic subtype (Table). There was no significant association between any of the three ancestral populations and clinical outcomes in the other 6 cancer types. Conclusions: We described clinical outcomes to ICIs across three global populations in 7 cancers. As the medical field re-evaluates the use of self-reported race in clinical decision-making, we utilize a novel ancestry pipeline that can be readily applied to tumor-only sequencing panels and better characterize non-white populations. We find no ancestry differences in clinical outcomes except in patients with RCC treated with ICIs which will require future validation. We plan to analyze genomic correlates of response by ancestry in each of the cancer types to better understand these diverge clinical behaviors.[Table: see text]
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Chan, WW, C. Ng, and TK Young. "Cross-Canada Forum – How we identify and count Aboriginal people—does it make a difference in estimating their disease burden?" Chronic Diseases and Injuries in Canada 33, no. 4 (September 2013): 277–80. http://dx.doi.org/10.24095/hpcdp.33.4.09.
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Introduction We examined the concordance between the Canadian Community Health Survey (CCHS) ''identity'' and ''ancestry'' questions used to estimate the size of the Aboriginal population in Canada and whether the different definitions affect the prevalence of selected chronic diseases. Methods Based on responses to the ''identity'' and ''ancestry'' questions in the CCHS combined 2009–2010 microdata file, Aboriginal participants were divided into 4 groups: identity only; ancestry only; either ancestry or identity; and both ancestry and identity. Prevalence of diabetes, arthritis and hypertension was estimated based on participants reporting that a health professional had told them that they have the condition(s). Results Of participants who identified themselves as Aboriginal, only 63% reported having an Aboriginal ancestor; of those who claimed Aboriginal ancestry, only 57% identified themselves as Aboriginal. The lack of concordance also differs according to whether the individual was First Nation, Métis or Inuit. The different method of estimating the Aboriginal population, however, does not significantly affect the prevalence of the three selected chronic diseases. Conclusion The lack of concordance requires further investigation by combining more cycles of CCHS to compare discrepancy across regions, genders and socio-economic status. Its impact on a broader list of health conditions should be examined.
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Pereira, Jaqueline L., Camila A. de Souza, Jennyfer E. M. Neyra, Jean M. R. S. Leite, Andressa Cerqueira, Regina C. M. Netto, Julia M. P. Soler, Marcelo M. Rogero, Flavia M. Sarti, and Regina M. Fisberg. "Genetic Ancestry and Self-Reported “Skin Color/Race” in the Urban Admixed Population of São Paulo City, Brazil." Genes 15, no. 7 (July 13, 2024): 917. http://dx.doi.org/10.3390/genes15070917.
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Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual’s genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.
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Johfre, Sasha Shen, Aliya Saperstein, and Jill A. Hollenbach. "Measuring Race and Ancestry in the Age of Genetic Testing." Demography 58, no. 3 (April 12, 2021): 785–810. http://dx.doi.org/10.1215/00703370-9142013.
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Abstract Will the rise of genetic ancestry tests (GATs) change how Americans respond to questions about race and ancestry on censuses and surveys? To provide an answer, we draw on a unique study of more than 100,000 U.S. adults that inquired about respondents' race, ancestry, and genealogical knowledge. We find that people in our sample who have taken a GAT, compared with those who have not, are more likely to self-identify as multiracial and are particularly likely to select three or more races. This difference in multiple-race reporting stems from three factors: (1) people who identify as multiracial are more likely to take GATs; (2) GAT takers are more likely to report multiple regions of ancestral origin; and (3) GAT takers more frequently translate reported ancestral diversity into multiracial self-identification. Our results imply that Americans will select three or more races at higher rates in future demographic data collection, with marked increases in multiple-race reporting among middle-aged adults. We also present experimental evidence that asking questions about ancestry before racial identification moderates some of these GAT-linked reporting differences. Demographers should consider how the meaning of U.S. race data may be changing as more Americans are exposed to information from GATs.
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Karacaören, Burak. "Admixture mapping of growth related traits in F2 mice dataset using ancestry informative markers." Journal of Bioinformatics and Computational Biology 12, no. 02 (April 2014): 1441010. http://dx.doi.org/10.1142/s0219720014410108.
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Most of the associated single nucleotide polymorphisms (SNPs) for genome wide association studies (GWAS) explain very little proportion of phenotypic variance in outbred populations. One reason is; large number of markers raises the problem of multiple hypothesis testing correction using conservative statistical tests in single marker models. Admixture mapping could be used as alternative model to detect the genes associated with quantitative traits by less number of ancestry informative markers. Ancestral genotypes of founder populations were available for the F 2 mice dataset for growth related traits. The objectives of this study were (1) to detect genomic signals by admixture mapping for growth related traits by ancestry informative markers and ancestral genotypes (2) to detect genomic signals for growth related traits by Bayes C(π) model and compare results with those obtained by use of admixture mapping. Bayes C(π) model detected more SNPs that has high ancestry informative markers. But due to stringent significance tests and small SNPs effects admixture model did not detect the same SNPs in Bayes C(π). As was expected higher ancestral informative markers lead to higher Z values in admixture model with a little variation. Admixture model could incorporate and use ancestral genomic information.
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Motegi, Tomoki, and Joshua D. Campbell. "Abstract C004: Assessing local ancestry inference using different sequencing assays and depth of coverage." Cancer Epidemiology, Biomarkers & Prevention 32, no. 12_Supplement (December 1, 2023): C004. http://dx.doi.org/10.1158/1538-7755.disp23-c004.
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Abstract Introduction: Several studies have reported differences in mutational frequencies between different ancestral populations. For example, PTEN alterations and TMPRSS2-ERG fusions are less common in men with African ancestry. However, these studies have primarily relied on measurements of "global ancestry" and have not been able to ascertain which genomic regions contribute to the observed differences in mutational frequencies. Recent advancements in computational algorithms now enable the estimation of “local ancestry” whereby individual chromosomal segments can be assigned to a particular ancestral background. These tools have been primarily developed for deep whole-genome sequencing (WGS) and have not been optimized for different sequencing assays including ultra-low pass WGS (ULP-WGS), whole exome sequencing (WES), and SNP genotyping arrays. The goal of our study is to establish best practices for local ancestry inference across a diverse set of sequencing and genotyping assays. Methods: We procured WGS data from four ancestries through the 1000 Genomes Project (n=1,067) for local ancestry inference. ULP-WGS and WES (with on- and off-target coverage) were simulated from the full WGS data. Pseudo-array data was emulated by restricting to SNP sites on Affymetrix Genome-Wide Human SNP array 6.0. Each genotype was imputed by Eagle-Beagle (EB) or GLIMPSE2 (GL2), and local ancestry inference was performed using G-nomix using window sizes spanning from 0.2 to 16.0 centimorgans (cM). Accuracy was assessed by comparing local ancestry calls for each assay in a training set (n=1007) to a validation set (n=62). Results: Local ancestry estimation in ULP-WGS data achieved an accuracy exceeding 98% when utilizing GL2, even with the smallest window size of 0.2 cM and a minimum sequencing depth of 0.1x. To achieve similar accuracy of 98% in ULP-WGS with EB, a window size of 1.5 cM was needed for sequencing depths from 2 to 0.5x, with a larger window size of 4 cM required for a depth of 0.25x. Interestingly, such accuracy did not obtain at a depth of 0.1x. For WES with on-target sites and pseudo-array data, we utilized EB for imputation as it was more computationally efficient and accurate with larger window sizes compared to GL2. The accuracy of WES with on-target sites exceeded 90% utilizing 4.0 cM or larger window sizes, but no window size achieved 98% accuracy. Incorporating off-target regions in WES and employing GL2 enhanced the accuracy to 98% at a window size of 1.5 cM. Pseudo-array data with EB achieved an accuracy of 98% at 0.5 cM and thus was better than WES. Conclusions: Our results show that local ancestry can be accurately estimated in different sequencing and genotyping assays when the window size and imputation tool are appropriately selected. This work will facilitate the use of local ancestry inference in studies utilizing different genotyping assays. Ultimately, researchers understand the influence of local ancestral haplotypes on molecular features of cancer. Citation Format: Tomoki Motegi, Joshua D. Campbell. Assessing local ancestry inference using different sequencing assays and depth of coverage [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C004.
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Arora, Kanika, Thinh N. Tran, Yelena M. Kemel, Miika Mehine, Ying Liu, Shaleigh A. Smith, Subhiksha Nandakumar, et al. "Abstract 2182: Ancestry inference and population-specific disparities in a real-world clinical sequencing cohort." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2182. http://dx.doi.org/10.1158/1538-7445.am2022-2182.
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Abstract Accurate ancestry inference is crucial for identifying genetic determinants of cancer disparities among specific populations. While methods to infer genetic ancestry and admixture have historically relied upon genome-wide markers from broad-scale next-generation sequencing (NGS), the adaptation to targeted NGS panels presents an opportunity to prospectively incorporate ancestry inference as part of routine clinical diagnosis. Here we show that global ancestral contributions and admixture of African (AFR), European (EUR), East Asian (EAS), Native American (NAM) and South Asian (SAS) populations can be reliably inferred using markers from genomic regions covered by the FDA-authorized clinical NGS panel, MSK-IMPACT. We also show that individuals with Ashkenazi Jewish (ASJ) ancestry can be inferred with 97% accuracy using a set of ASJ ancestry-informative markers. We apply these methods to infer genetic ancestry for over 45,000 patients from the AACR GENIE v10.0-public cohort who were profiled using MSK-IMPACT. We observed 98% concordance between self-reported race and genetic ancestry for non-admixed individuals and were able to quantitatively infer ancestral contributions for individuals from recently admixed populations such as African American and Latin American. Of the discordant cases, manual review of clinical and family histories revealed the vast majority to represent clinical encoding errors where the inferred ancestry was confirmed correct. As self-reported race is not available for 17% of patients in the GENIE cohort, the ability to accurately infer genetic ancestry enables broader analysis of population-specific genomic and clinical features. We systematically evaluated the frequency of somatic and germline alterations in up to 468 genes for each cancer type and recapitulated known differences among ancestral populations. For example, we observed significantly higher frequency of EGFR somatic alterations in EAS (65%) and SAS (66%) compared to non-ASJ EUR (21%) with lung adenocarcinoma, a difference that remained significant even when limiting to never-smokers. Additionally, we found that the frequency of harboring at least one known BRCA founder mutation (BRCA1 68_69delAG, BRCA1 5266dupC, or BRCA2 5946delT) was 26x higher in genetically determined ASJ (5.1%) compared to non-ASJ (0.2%). Strikingly, while the overall rate of driver alterations in solid tumors was similar across different populations, we found that the proportion of patients with clinically actionable somatic alterations (OncoKB Level 1, 2, 3A, or 3B) was lowest in AFR (47%) patients compared to EUR, EAS and SAS (50% each). While this result is partially explained by different cancer type and subtype distributions in different populations in this real-world cohort, it highlights the urgency for greater equity in drug development programs to target alterations represented across all diverse populations. Citation Format: Kanika Arora, Thinh N. Tran, Yelena M. Kemel, Miika Mehine, Ying Liu, Shaleigh A. Smith, Subhiksha Nandakumar, Irina Ostrovnaya, Thomas C. Reynolds, Kenneth Offit, David Solit, Marc Ladanyi, Nikolaus Schultz, Ahmet Zehir, Carol L. Brown, Debyani Chakravarty, Zsofia K. Stadler, Chaitanya Bandlamudi, Michael F. Berger. Ancestry inference and population-specific disparities in a real-world clinical sequencing cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2182.
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Russo, María Gabriela, Francisco Di Fabio Rocca, Patricio Doldán, Darío Gonzalo Cardozo, Cristina Dejean, Verónica Seldes, and Sergio Avena. "EVALUACIÓN DEL NÚMERO MÍNIMO DE MARCADORES PARA ESTIMAR ANCESTRÍA INDIVIDUAL EN UNA MUESTRA DE LA POBLACIÓN ARGENTINA / Evaluation of the minimum number of markers for individual ancestry estimation in an Argentinean population sample." Revista del Museo de Antropología 9, no. 1 (June 22, 2016): 49. http://dx.doi.org/10.31048/1852.4826.v9.n1.12579.
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<p>La estimación de ancestría individual posee gran relevancia en el estudio de la composición poblacional en regiones como Sudamérica, que han atravesado intensos procesos de mestizaje, lo que también tiene implicancia en ciencias de la salud. Debido a esto, es importante conocer los factores que influyen en la confiabilidad de los resultados obtenidos. En este trabajo se evalúa el número mínimo de marcadores informativos de ancestría (AIMs) a partir del cual las estimaciones resultarían aceptables. Se toma como ejemplo el cálculo en individuos provenientes de una muestra poblacional de diferentes regiones de Argentina. Considerando un modelo de tres componentes (nativo americano, euroasiático y subsahariano), se calculó la ancestría de 441 individuos utilizando 10, 20, 30 y 50 AIMs. Los resultados indican que el número de marcadores influye sobre la estimación de ancestría y su precisión aumenta al incrementarse la cantidad de AIMs. Al comparar con las estimaciones obtenidas en un trabajo previo a partir de 99 AIMs, se observó que para el componente minoritario (en este caso subsahariano) se obtiene una buena correlación utilizando al menos 30 marcadores. Se concluye que es necesario considerar en los estudios de ancestría individual el número de marcadores, su capacidad informativa y las características de la población bajo estudio.</p><p><br /><strong>Abstract</strong></p><p><br />Estimation of individual ancestry has great relevance when studying population composition in regions like South America, where intensive admixture processes have occurred, being also important in biomedical sciences. For that reason, it is important to assess the factors that may affect the reliability of results. In this work, we investigate the minimum number of ancestry informative markers (AIMs) for obtaining acceptable estimations of ancestry. As an example, we take individuals from a population sample of different Argentinean regions. Considering a three component model (Native American, Eurasian and Sub-Saharan), we calculated ancestry of 441 individuals using 10, 20, 30 and 50 AIMs. The results indicate that the number of markers affects ancestry estimation and its accuracy increases with AIMs number. When compared to previous estimations obtained from 99 AIMs, the result shows that at least 30 markers are needed to achieve good correlation values for the minority component (Sub-Saharan in this case). For individual ancestry studies, we suggest to take into account not only the number of markers, but also its informativeness and the background of the studied population.</p>
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Pereira, Fabiana dos Santos Carolino Firmo, Raphael Mendonça Guimarães, Alexandre Ramos Lucidi, and Regina Maria Papais Alvarenga. "Frequency of family forms of multiple sclerosis in a center in Rio de Janeiro." Concilium 23, no. 16 (August 21, 2023): 15–27. http://dx.doi.org/10.53660/clm-1838-23m45.
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Familial multiple sclerosis(fMS) is defined as multiple sclerosis cases occurring in at least two family members, and there is no data on the recurrence risk of fMS in the Brazilian population. This study estimated the multiple sclerosis recurrence risk in patient families in RJ and investigated the relationship with Caucasian and African ancestry. A study was conducted in RJ (Brazil), with 197 patients followed by a RJ specialized outpatient clinic. Recurrence risks were calculated by relative MS patient categories through Age-adjusted and Crude recurrence risks. fMS frequency (7.10%) was identified in the RJ study population. The risk of Age-adjusted recurrence (ARR) was high among grandparents, at 2.72 (95% CI 2.16 - 3.28). Concerning the parent relationship, ARR was 1.57 (95% CI 1.36 - 1.78) and increased to 1.76 (95% CI 1.41 - 2.11) in the presence of a European ancestor. Among uncles/aunts, a significant increase from 1.42 (95% CI 1.01 - 1.83) to 2.91 (95% CI 2.28 - 3.54) risk in individuals with Caucasian ancestry was observed, and to 2.65 (95% CI 2.02 - 3.27) in individuals with African ancestry. A higher risk among individuals with Caucasian ancestry was observed compared to Afro-descendant ancestry.
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Matsen, Frederick A., and Steven N. Evans. "To what extent does genealogical ancestry imply genetic ancestry?" Theoretical Population Biology 74, no. 2 (September 2008): 182–90. http://dx.doi.org/10.1016/j.tpb.2008.06.003.
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Calfee, Erin, Daniel Gates, Anne Lorant, M. Taylor Perkins, Graham Coop, and Jeffrey Ross-Ibarra. "Selective sorting of ancestral introgression in maize and teosinte along an elevational cline." PLOS Genetics 17, no. 10 (October 11, 2021): e1009810. http://dx.doi.org/10.1371/journal.pgen.1009810.
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While often deleterious, hybridization can also be a key source of genetic variation and pre-adapted haplotypes, enabling rapid evolution and niche expansion. Here we evaluate these opposing selection forces on introgressed ancestry between maize (Zea mays ssp. mays) and its wild teosinte relative, mexicana (Zea mays ssp. mexicana). Introgression from ecologically diverse teosinte may have facilitated maize’s global range expansion, in particular to challenging high elevation regions (> 1500 m). We generated low-coverage genome sequencing data for 348 maize and mexicana individuals to evaluate patterns of introgression in 14 sympatric population pairs, spanning the elevational range of mexicana, a teosinte endemic to the mountains of Mexico. While recent hybrids are commonly observed in sympatric populations and mexicana demonstrates fine-scale local adaptation, we find that the majority of mexicana ancestry tracts introgressed into maize over 1000 generations ago. This mexicana ancestry seems to have maintained much of its diversity and likely came from a common ancestral source, rather than contemporary sympatric populations, resulting in relatively low FST between mexicana ancestry tracts sampled from geographically distant maize populations. Introgressed mexicana ancestry in maize is reduced in lower-recombination rate quintiles of the genome and around domestication genes, consistent with pervasive selection against introgression. However, we also find mexicana ancestry increases across the sampled elevational gradient and that high introgression peaks are most commonly shared among high-elevation maize populations, consistent with introgression from mexicana facilitating adaptation to the highland environment. In the other direction, we find patterns consistent with adaptive and clinal introgression of maize ancestry into sympatric mexicana at many loci across the genome, suggesting that maize also contributes to adaptation in mexicana, especially at the lower end of its elevational range. In sympatric maize, in addition to high introgression regions we find many genomic regions where selection for local adaptation maintains steep gradients in introgressed mexicana ancestry across elevation, including at least two inversions: the well-characterized 14 Mb Inv4m on chromosome 4 and a novel 3 Mb inversion Inv9f surrounding the macrohairless1 locus on chromosome 9. Most outlier loci with high mexicana introgression show no signals of sweeps or local sourcing from sympatric populations and so likely represent ancestral introgression sorted by selection, resulting in correlated but distinct outcomes of introgression in different contemporary maize populations.
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Simmons, Timothy, Elisha Hughes, Dmitry Pruss, Matthew Kucera, Benjamin Roa, Thaddeus Judkins, Thomas Slavin, et al. "Abstract PS10-07: A second-generation polygenic risk score (PRS) based on genetic ancestry improves breast cancer (BC) risk prediction for all ancestries." Cancer Research 84, no. 9_Supplement (May 2, 2024): PS10–07—PS10–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-ps10-07.
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Abstract Background: Common genetic variants, mainly single-nucleotide polymorphisms (SNPs) explain substantial genetic susceptibility to BC. PRS have been developed to quantify the combined effects of BC-associated SNPs, providing important information about BC risk. Historically, genome-wide association studies have been conducted in predominantly European populations, resulting in miscalibrated and inaccurate PRS for non-Europeans. We previously described a multiple-ancestry PRS (MA-PRS-149) based on 56 ancestry-informative and 93 BC-associated SNPs. The MA-PRS-149 achieved accuracy for all women by characterizing the genetic ancestry of each BC-associated SNP in terms of three reference ancestries (African, East Asian, and European), applying ancestry-specific SNP risks and frequencies, and combining the results as a weighted sum of three ancestry-specific PRS. Here, we aimed to improve the predictive accuracy of MA-PRS-149, particularly for non-Europeans, through the inclusion of additional BC-associated SNPs. Methods: Women referred for hereditary cancer testing and negative for pathogenic variants in BC-associated genes were divided into consecutive study cohorts to (1) quantify ancestry-specific SNP risks, (2) combine the three ancestry-specific PRS, and (3) pre-specified clinical validation. To select an optimal set of BC-associated SNPs, we developed a novel synthetic stepwise regression methodology that accounts for linkage disequilibrium. Ancestry-specific SNP risks were determined from meta-analyses of literature with clinical cohorts of 57,827 Black/African and 26,992 East Asian women. Ancestry-specific PRS were combined based on a diverse cohort of 157,740 women. Clinical validation was conducted in an independent cohort of 77,774 women. We used multivariable logistic regression adjusted for age, ancestry, and cancer history to test for improved BC risk prediction over clinical factors. We tested for improvement over the MA-PRS-149, and a European PRS, by including additional PRS as covariates. Calibration was assessed through goodness-of-fit tests. All analyses were conducted within the full cohort and ancestral subpopulations. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported per standard deviation within the corresponding population. Results: An optimal set of 383 SNPs (56 ancestry-informative and 327 BC-associated) was included in the final PRS (MA-PRS-383). MA-PRS-383 added significant predictive information to clinical factors in the full cohort and within each ancestry (Table 1). MA-PRS-383 had greater predictive accuracy than MA-PRS-149 or a 383-SNP PRS with European weights. Goodness-of-fit tests showed that MA-PRS-383 was well-calibrated and predicted risk accurately in the tails of the distribution for both European and non-European women. Conclusion: MA-PRS-383 was well-calibrated and substantially improved upon existing PRS in all tested ancestral populations. Incorporation of MA-PRS-383 into BC risk assessment may lead to more accurate identification of women who are most likely to benefit from screening and preventive medications. Citation Format: Timothy Simmons, Elisha Hughes, Dmitry Pruss, Matthew Kucera, Benjamin Roa, Thaddeus Judkins, Thomas Slavin, Victor Abkevich, Ryan Hoff, Srikanth Jammulapati, Susanne Wagner, Dale Muzzey, Jerry Lanchbury, Alexander Gutin. A second-generation polygenic risk score (PRS) based on genetic ancestry improves breast cancer (BC) risk prediction for all ancestries [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-07.
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Tvedebrink, Torben. "Review of the Forensic Applicability of Biostatistical Methods for Inferring Ancestry from Autosomal Genetic Markers." Genes 13, no. 1 (January 14, 2022): 141. http://dx.doi.org/10.3390/genes13010141.
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The inference of ancestry has become a part of the services many forensic genetic laboratories provide. Interest in ancestry may be to provide investigative leads or identify the region of origin in cases of unidentified missing persons. There exist many biostatistical methods developed for the study of population structure in the area of population genetics. However, the challenges and questions are slightly different in the context of forensic genetics, where the origin of a specific sample is of interest compared to the understanding of population histories and genealogies. In this paper, the methodologies for modelling population admixture and inferring ancestral populations are reviewed with a focus on their strengths and weaknesses in relation to ancestry inference in the forensic context.
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Sun, Hanxiao, Meng Lin, Emily M. Russell, Ryan L. Minster, Tsz Fung Chan, Bryan L. Dinh, Take Naseri, et al. "The impact of global and local Polynesian genetic ancestry on complex traits in Native Hawaiians." PLOS Genetics 17, no. 2 (February 11, 2021): e1009273. http://dx.doi.org/10.1371/journal.pgen.1009273.
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Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry (“global ancestry,” which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome (“local ancestry”) and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic (P = 1.65×10−4) and having heart failure (P = 2.18×10−4), as well as a 0.059 s.d. increase in BMI (P = 1.04×10−10). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D.
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Zhang, Chenan, Quinn T. Ostrom, Helen M. Hansen, Julio Gonzalez-Maya, Donglei Hu, Elad Ziv, Libby Morimoto, et al. "European genetic ancestry associated with risk of childhood ependymoma." Neuro-Oncology 22, no. 11 (June 2, 2020): 1637–46. http://dx.doi.org/10.1093/neuonc/noaa130.
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Abstract Background Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations. Methods In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS). Results CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08–1.59, Pmeta = 6.7 × 10−3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45–2.73; P = 2.2 × 10−5) but which was not validated in an independent set of posterior fossa type A patients. Conclusions Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.