Role Of Ancestry Research Articles

Influence of ancestry in racial disparities of squamous cell lung cancer.

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.

The Lord’s Goodbye / Bertilak’s Ghazal and Antigone Regina

With The Lord’s Goodbye / Bertilak’s Ghazal, I wanted to give myself the challenge of incorporating the Arthurian legend into the Medieval Persian ghazal form. The ghazal’s stylistic characteristics are incredibly fascinating and unique compared to traditional Western forms, especially the rhyming patterns. I realised I also found this stylistic distinctiveness in Medieval poems, notably ‘Sir Gawain and the Green Knight’, with its unique alliterative form. This poem draws similarities between the themes generally explored in a ghazal (abandonment, love, and religious imagery) and the story of Sir Gawain. I created a deliberate ambiguity between the two female characters, respectively described as her and Her (the capitalisation reinforcing the religious aspects of the Virgin Mary, who has a major role in the poem). The erotic connotations of Gawain’s relationship with Bertilak also helped with adapting the ghazal to the Arthurian genre. Through this poem, I hope to illustrate the malleability of the myth; a modern Arthurian retelling could deal with queer themes and interpretations, for example, or explore its influence outside of the Western psyche from a non-European perspective. I wrote Antigone Regina to experiment with the triolet form and to expand on the father-daughter relationship in Sophocles’ Oedipus at Colonus. My favourite aspect of this form is the opportunity to make the same line take different meanings through the poem. The line ‘Oedipus’ grave and weeping blood’ plays on the word ‘grave’, hence the comma that appears in the last line. I also wanted to draw on the relationship that various retellings of the myth placed between humans and gods, as well as the role of ancestry and inheritance – not as a curse, but a fundamental part of human experience on both the individual and the societal level. Although this poem does not explicitly deal with the Arthurian story, it therefore still speaks of the role of poems as important reinterpretations of a myth.

Gaelic and Identity: A Response to Iain MacKinnon

This article responds to the recent special issue of Scottish Affairs on ‘Gàidhealtachd Futures’ and in particular the article by Iain MacKinnon proposing that ancestry, ethnicity and indigeneity should become the principal elements in contemporary Gaelic identity. The editors of the special issue do not give an analytically meaningful presentation of the term Gàidhealtachd and MacKinnon fails to give a complete or balanced account of previous research on the question of Gaelic identity. There is considerable uncertainty about how the term Gael is understood today; many Gaelic speakers are reluctant to accept this label for themselves. MacKinnon's arguments concerning the role of ancestry in defining Gaelic identity are highly problematic in both analytical and political terms. His proposals concerning ethnicity and indigeneity are unsustainable, particularly in light of relevant legal standards, and amount to a strategic, ethical and legal dead end for the Gaelic revitalisation movement.

Inferred Ancestral Origin of Cancer Cell Lines Associates with Differential Drug Response.

Disparities between risk, treatment outcomes and survival rates in cancer patients across the world may be attributed to socioeconomic factors. In addition, the role of ancestry is frequently discussed. In preclinical studies, high-throughput drug screens in cancer cell lines have empowered the identification of clinically relevant molecular biomarkers of drug sensitivity; however, the genetic ancestry from tissue donors has been largely neglected in this setting. In order to address this, here, we show that the inferred ancestry of cancer cell lines is conserved and may impact drug response in patients as a predictive covariate in high-throughput drug screens. We found that there are differential drug responses between European and East Asian ancestries, especially when treated with PI3K/mTOR inhibitors. Our finding emphasizes a new angle in precision medicine, as cancer intervention strategies should consider the germline landscape, thereby reducing the failure rate of clinical trials.

Towards unravelling Wolbachia global exchange: a contribution from the Bicyclus and Mylothris butterflies in the Afrotropics

BackgroundPhylogenetically closely related strains of maternally inherited endosymbiotic bacteria are often found in phylogenetically divergent, and geographically distant insect host species. The interspecies transfer of the symbiont Wolbachia has been thought to have occurred repeatedly, facilitating its observed global pandemic. Few ecological interactions have been proposed as potential routes for the horizontal transfer of Wolbachia within natural insect communities. These routes are however likely to act only at the local scale, but how they may support the global distribution of some Wolbachia strains remains unclear.ResultsHere, we characterize the Wolbachia diversity in butterflies from the tropical forest regions of central Africa to discuss transfer at both local and global scales. We show that numerous species from both the Mylothris (family Pieridae) and Bicyclus (family Nymphalidae) butterfly genera are infected with similar Wolbachia strains, despite only minor interclade contacts across the life cycles of the species within their partially overlapping ecological niches. The phylogenetic distance and differences in resource use between these genera rule out the role of ancestry, hybridization, and shared host-plants in the interspecies transfer of the symbiont. Furthermore, we could not identify any shared ecological factors to explain the presence of the strains in other arthropod species from other habitats, or even ecoregions.ConclusionOnly the systematic surveys of the Wolbachia strains from entire species communities may offer the material currently lacking for understanding how Wolbachia may transfer between highly different and unrelated hosts, as well as across environmental scales.

Relationship Between Mitochondrial DNA Mutations and Aging. Estimation of Age-at-death.

Some studies have pointed to the relationship between mitochondrial DNA (mtDNA) mutations and age in different tissues, which are potentially interesting in aging research and in forensic identification because they could help to improve the estimation of age-at-death. The present study aims to evaluate the mutations in mtDNA from dentin and pulp and their relation with age. Healthy erupted third molars were extracted from individuals from two Spanish populations, aged 20-70. When analyzing the amplification of hypervariable region 2 of the mtDNA by real-time polymerase chain reaction, a negative strong linear correlation was found between the mtDNA amplification and age in dentin from both populations. In contrast, a significant correlation between mtDNA amplification and age in pulp was not discovered, probably due to the majority of the mitochondria are placed in dentin. A difference in mtDNA damage between these two populations was also detected, indicating the role of ancestry as a component. The findings from this research enrich the current studies related to aging and mitochondrial damage and provide a new quantitative tool for estimating the age-at-death that, in combination with traditional age markers, could improve identification accuracy in forensic cases.

The role of ancestry in TB susceptibility of an admixed South African population

Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC.

Blood Pressure Genetics and Hypertension: Genome-Wide Analysis and Role of Ancestry

Genome-wide association studies have been successful in identifying an increasing number of loci as associated with blood pressure and hypertension. However, most studies undertaken to date have only included individuals of European-ancestry for discovery of loci. Although there are differences in the prevalence and incidence of cardiovascular diseases between ancestries, it is expected that a common set of genomic loci will have an underlying involvement in blood pressure across ancestries with differences in genetic effect sizes due to ancestry-related differences in linkage disequilibrium (with the true causal variant) and environmental interactions. The differences in genetic variation between ancestries, for example, linkage disequilibrium structure and allele frequencies, can be exploited to identify additional loci associated with blood pressure traits and also to fine-map signals. This review will summarise the findings to date and discuss approaches for testing association with blood pressure across different ancestries.

Human Biological Variation in Anatomy Textbooks: The Role of Ancestry

Human Biological Variation in Anatomy Textbooks: The Role of Ancestry

Human Biological Variation in Anatomy Textbooks: The Role of Ancestry

Humans vary biologically at different levels: individually, according to sex, age and ancestry. The first three levels are usually competently accounted for in medical curriculum, but this does not...

The contribution of ancestry, chance, and past and ongoing selection to adaptive evolution.

The relative contributions of ancestry, chance, and past and ongoing selection to variation in one adaptive (larval feeding rate) and one seemingly nonadaptive (pupation height) trait were determined in populations of Drosophila melanogaster adapting to either low or high larval densities in the laboratory. Larval feeding rates increased rapidly in response to high density, and the effects of ancestry, past selection and chance were ameliorated by ongoing selection within 15-20 generations. Similarly, in populations previously kept at high larval density, and then switched to low larval density, the decline of larval feeding rate to ancestral levels was rapid (15-20 generations) and complete, providing support for a previously stated hypothesis regarding the costs of faster feeding in Drosophila larvae. Variation among individuals was the major contributor to variation in pupation height, a trait that would superficially appear to be nonadaptive in the environmental context of the populations used in this study because it did not diverge between sets of populations kept at low versus high larval density for many generations. However, the degree of divergence among populations (F(ST)) for pupation height was significantly less than expected for a selectively neutral trait, and we integrate results from previous studies to suggest that the variation for pupation height among populations is constrained by stabilizing selection, with a flat, plateau-like fitness function that, consequently, allows for substantial phenotypic variation within populations. Our results support the view that the genetic imprints of history (ancestry and past selection) in outbreeding sexual populations are typically likely to be transient in the face of ongoing selection and recombination. The results also illustrate the heuristic point that different forms of selection-for example directional versus stabilizing selection-acting on a trait in different populations may often not be due to differently shaped fitness functions, but rather due to differences in how the fitness function maps onto the actual distribution of phenotypes in a given population. We discuss these results in the light of previous work on reverse evolution, and the role of ancestry, chance, and past and ongoing selection in adaptive evolution.