Genetic History Research Articles

Population Genetics and Invasion History of the European Starling Across Aotearoa New Zealand.

The expansion of human settlements over the past few centuries is responsible for an unprecedented number of invasive species introductions globally. An important component of biological invasion management is understanding how introduction history and postintroduction processes have jointly shaped present-day distributions and patterns of population structure, diversity and adaptation. One example of a successful invader is the European starling (Sturnus vulgaris), which was intentionally introduced to numerous countries in the 19th century, including Aotearoa New Zealand, where it has become firmly established. We used reduced representation sequencing to characterise the genetic population structure of the European starling in New Zealand, comparing it to that present in sampling locations in the native range and invasive Australian range. The population structure and genetic diversity patterns we found suggested restricted gene flow from the majority of New Zealand to the northmost sampling location (Auckland). We also profiled genetic bottlenecks and shared outlier genomic regions, which supported historical accounts of translocations between both Australian subpopulations and New Zealand, and provided evidence of which documented translocation events were more likely to have been successful. Using these results as well as historic demographic patterns, we demonstrate how genomic analysis complements even well-documented invasion histories to better understand invasion processes, with direct implications for understanding contemporary gene flow and informing invasion management.

Obesity as a medical and social problem

The article is a brief review of the relevant scientific literature published in the PubMed database in 2004–2024 on the epidemiology, etiology, treatment and prevention of obesity. The description of the key risk factors for the development of obesity is given, among them genetic factors, family history, psychological causes, and anesthetic marketing. The data on modern approaches to the treatment of obesity, including adherence to a low-calorie diet, adequate physical activity, taking medications that reduce appetite, enhance the feeling of satiety and reduce fat metabolism, are presented. It is noted that it is necessary to implement measures that lie outside the competence of medical organizations, such as ensuring the availability of healthy food and limiting the availability of fast food, changing the formulation of high-calorie products, labeling products and educating the population.

Risk Factors of Agitation Among Schizophrenia Patients in Dr. Amino Gondohutomo Semarang Regional Psychiatric Hospital: A Cross-Sectional Study

Introduction: Schizophrenia is a severe mental disorder associated with deterioration in the functions of daily life and social functions because it can reduce a person’s quality of life. In the acute phase, many schizophrenic patients have agitated behavior where this behavior will risk injuring themselves and others because of that treatment costs increase. to determine the risk factors for agitation in schizophrenic patients in terms of age, gender, marital status, occupation, genetic history, and presence or absence of stressors. Methods: This research is a descriptive analytic using a cross-sectional design. The population in this study were schizophrenic patients at Dr. Amino Gondohutomo Semarang Regional Psychiatric Hospital. Research subjects will be taken using consecutive sampling techniques that meet the inclusion and exclusion criteria. Data collection used medical record data and the PANNS EC score to determine whether there was agitation. Data analysis included descriptive analysis with frequency and percentage distributions as well as hypothesis testing using the Chi Square test and logistic regression. Results: From the results of the Chi Square test and logistic regression, it was found that the factors of young age, male sex, unmarried, and unemployed were significant for PANSS EC with a prevalence value of 3.40 (1.13 – 10.22), 2.01 (1.14 – 3.56), 2.39 (1.36 – 4.20), and 2.07 (1.12 – 3.83). Conclusion: Factors of young age <40 years, male sex, unmarried, and unemployed are risk factors for the occurrence of agitation in schizophrenic patients at Dr. Amino Gondohutomo Semarang Regional Psychiatric Hospital.

Temporal recording of mammalian development and precancer

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations1,2, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering3–5. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell types and new epithelial progenitor states by their unique genetic histories. Analysis of mouse adenomas, coupled to multiomic and single-cell profiling of human precancers, with clonal analysis of 418 human polyps, demonstrated the occurrence of polyclonal initiation in 15–30% of colonic precancers, showing their origins from multiple normal founders. Our study presents a multimodal framework that lays the foundation for in vivo recording, integrating synthetic or natural indelible genetic changes with single-cell analyses, to explore the origins and timing of development and tumorigenesis in mammalian systems.

Y chromosome sequencing data suggest dual paths of haplogroup N1a1 into Finland.

The paternally inherited Y chromosome is highly informative of genetic ancestry, therefore making it useful in studies of population history. In Finland, two Y-chromosomal haplogroups reveal the major substructure of the population: N1a1 enriched in the northeast and I1a in the southwest, suggested to reflect eastern and western ancestry contributions to the population. Yet, beyond these major Y-chromosomal lineages, the distribution of finer-scale Y-chromosomal variation has not been assessed in Finland. Here, we provide the most comprehensive Y-chromosomal study among the Finns to date, exploiting sequences for 1802 geographically mapped Finnish Y chromosomes from the FINRISK project. We assessed the distribution of common Y-chromosomal haplogroups (frequency ≥1%) throughout 19 Finnish regions and compared the autosomal genetic backgrounds of the Y-chromosomal haplogroups. With such high-resolution data, we were able to find previously unreported sublineages and resolve phylogenetic relationships within haplogroups N1a1 (64%), I1a (25%), R1a (4.3%), and R1b (4.8%). We further find novel geographical enrichment patterns among these Y-chromosomal haplogroups, most notably observed for haplogroup N1a1 dividing into two lineages with differing distributions. While sublineage N-Z1934 (42%) followed a northeastern enrichment pattern observed for all N1a1 carriers in general, sublineage N-VL29 (22%) displayed an enrichment in the southwest. Further, the carriers of N-VL29 showed a higher proportion of southwestern autosomal ancestry compared to carriers of N-Z1934. Collectively, these results point to distinct demographics within haplogroup N1a1, possibly induced by two distinct arrival routes into Finland. Overall, our study suggests a more complex genetic population history for Finns than previously proposed.

Genetic Code Expansion History and Modern Innovations.

The genetic code is the foundation for all life. With few exceptions, the translation of nucleic acid messages into proteins follows conserved rules, which are defined by codons that specify each of the 20 proteinogenic amino acids. For decades, leading research groups have developed a catalogue of innovative approaches to extend nature's amino acid repertoire to include one or more noncanonical building blocks in a single protein. In this review, we summarize advances in the history of in vitro and in vivo genetic code expansion, and highlight recent innovations that increase the scope of biochemically accessible monomers and codons. We further summarize state-of-the-art knowledge in engineered cellular translation, as well as alterations to regulatory mechanisms that improve overall genetic code expansion. Finally, we distill existing limitations of these technologies into must-have improvements for the next generation of technologies, and speculate on future strategies that may be capable of overcoming current gaps in knowledge.

Genetic typication of boxites of the Futa province of Jallon-Mandingo (West Africa) by textural and structural features

In the process of the formation of classical lateritic bauxites in the Futa Jallon-Mandingo province, due to a complex of two-three-stage genesis, different lithological and genetic types of bauxites were formed in external characteristics, color, texture, structure. The proposed genetic typification of bauxite, based on the textural and structural features of the rocks, in fact is the basis for the geological and industrial classification of deposits of the region. Studying the textural and structural features of bauxites is the only way through which one can get an idea of the conditions of their formation. It is in the textures and structures of ores their genetic history is imprinted. The analysis shows that the deposits, within which deposits of sedimentary-lateritic and chemically transformed bauxites predominate, are distinguished not only by greater thicknesses of ore bodies and a significantly higher content of total alumina in the ores, but also by increased contents of monohydrate forms. This also determines various economic indicators of the operation and technology of metallurgical processing of bauxite.

Nested admixture during and after the Trans-Atlantic Slave Trade on the island of São Tomé.

Human admixture history is rarely a simple process in which distinct populations, previously isolated for a long time, come into contact once to form an admixed population. In this study, we aim to reconstruct the complex admixture histories of the population of São Tomé, an island in the Gulf of Guinea that was the site of the first slave-based plantation economy, and experienced successive waves of forced and deliberate migration from Africa. We examined 2.5 million SNPs newly genotyped in 96 São Toméans and found that geography alone cannot explain the observed patterns of genetic differentiation within the island. We defined five genetic groups in São Tomé based on the hypothesis that individuals sharing the most haplotypes are more likely to share similar genetic histories. Using Identical-by-Descent and different local ancestry inference methods, we inferred shared ancestries between 70 African and European populations and each São Toméan genetic group. We identified admixture events between admixed groups that were previously isolated on the island, showing how recently admixed populations can be themselves the sources of other admixture events. This study demonstrates how complex admixture and isolation histories during and after the Transatlantic Slave-Trade shaped extant individual genetic patterns at a local scale in Africa.

ABCA3 c.838C>T (p.Arg280Cys, R280C) and c.697C>T (p.Gln233Ter, Q233X, Q233*) as Causative Variants for RDS: A Family Case Study and Literature Review.

Background: Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature are inconsistent. Material and Methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, which was not previously reported but is a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, an analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade

Lung cancer brain metastasis (LCBM) poses a significant clinical challenge due to acquired resistance to tyrosine kinase inhibitor (TKI) treatment. To elucidate its underlying mechanisms, we employed single-cell RNA sequencing analysis on surgically obtained LCBM samples with diverse genetic backgrounds and TKI treatment histories. Our study uncovers that TKI treatment elevates the immune checkpoint CTLA4 expression in Tcells, promoting an immune-suppressive microenvironment. This immunomodulation is initiated by tumor-derived HMGB1 in response to TKIs. In LCBM syngeneic murine models with TKI-sensitive or TKI-resistant EGFR mutations, combining CTLA4 blockade with TKIs demonstrates enhanced efficacy over TKI monotherapy or TKIs with PD1 blockade. These findings provide insights into the TKI resistance mechanisms and highlight the potential of CTLA4 blockade in effectively overcoming TKI resistance in LCBM.

The case against simplistic genetic explanations of evolution.

Humans are curious to understand the causes of traits that distinguish us from other animals and that distinguish vastly different species from one another. We also have a proclivity for simple stories and sometimes tend toward seeking and accepting simple genetic explanations for large evolutionary shifts, even to a single gene. Here, I reveal how a biased expectation of mechanistic simplicity threads through the long history of evolutionary and developmental genetics. I argue, however, that expecting a simple mechanism threatens a deeper understanding of evolution, and I define the limitations for interpreting experimental evidence in evolutionary developmental genetics.

A ten-year overview of cancer genetic family history screening in Georgia's Latina population.

Population-based cancer genetic family history (FH) screening to identify families at high risk for BRCA-associated cancers has been endorsed by national public health policies. This report aimed to describe the utilization of FH screening services from 2013 to 2022 according to rurality and socioeconomic deprivation among Latinas in Georgia. Women who attended a medical appointment at participating Georgia Public Health Clinics were invited to complete FH screening. Screening results and participant zip code were reviewed. Area deprivation index (ADI) was measured at the census block group level and dichotomized (more deprived and less deprived). Rurality was measured through Rural-Urban Commuting Area (RUCA) codes and dichotomized (urban and rural). The ADI and RUCA codes were linked to participant data by zip code to characterize FH utilization among the Latina community. Of the 9,330 adult Latinas in Georgia that completed cancer genetic FH screening, 9,066 (97.17%) women screened negative, and 264 (2.83%) screened positive (i.e., FH suggestive of higher risk for carrying BRCA1/2 mutations compared to the general population). Screening completion was higher among Latinas in urban areas (n = 7,871) compared to rural areas (n = 1,459). Screening completion was also higher in more socially deprived areas (n = 5,207) compared to less socially deprived areas (n = 4,123). Georgia's FH screening program reached Latinas across Georgia, particularly those living in urban, socially deprived areas. To ensure equitable cancer genetic screening dissemination, future efforts should prioritize tailored outreach in rural regions and comprehensive evaluations to identify key determinants of screening trends among Georgia's Latina population.

Long Non-coding RNA and Progression of Breast Cancer

Breast cancer is a major problem in the health sector worldwide. The prevalence of breast cancer incidence is on the rise in many countries despite efforts to eradicate it. The substantial efforts for the treatment of breast cancer are quite successful but the main hindrance is early detection which in turn is dependent on various factors i.e. genetic history, environmental exposures, hormonal causes, and sedentary lifestyle. In previous studies, lncRNAs were known to modulate the progression of many cancers like gastric, lung, ovarian, and colorectal cancers. This study was designed to find these lncRNAs role in breast cancer development. Bioinformatics tools were used for in silco analysis of these lncRNAs LINC01356, LINC01357, ARF4-AS1, and FAM83B. These lncRNAs were evaluated in GEPIA2 for subtype analysis and survival probability, Phylo CSF UCSC genome browser for conserved sequences and protein-coding potential, BcGenExMiner for correlation analysis and UALCAN for protein-coding gene expression. These above-mentioned lncRNAs showed high expression in the basal subtype of TNBC as compared with other subtypes and they showed poor survival rates in the basal subtype. LINC01356 and LINC01357 showed positive correlation with TAFA3 and SLC16A1. ARF4-AS1 positively correlated with ASB14 and FAM83B positively correlated with HCRTR2. These lncRNAs showing positive correlation with different genes have a role in breast cancer development and progression.

Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy.

Understanding the genetic basis of human diseases has become integral to drug development and precision medicine. Recent advancements have enabled the identification of molecular pathways driving diseases, leading to targeted treatment strategies. The increasing investment in rare diseases by the biotech industry underscores the importance of genetic evidence in drug discovery and approval processes. Here we studied a monogenic Mendelian kidney disease, TRPC6-associated podocytopathy (TRPC6-AP), to present its natural history, genetic spectrum, and clinicopathological associations in a large cohort of patients with causal variants in TRPC6, in order to help define the specific features of disease and further facilitate drug development and clinical trials design. the study involved 64 individuals from 39 families with TRPC6 causal missense variants. Clinical data, including age of onset, laboratory results, response to treatment, kidney biopsy findings, and genetic information, were collected from multiple centers nationally and internationally. Exome or targeted sequencing was performed and variant classification was based on strict criteria. Structural and functional analyses of TRPC6 variants were conducted to understand their impact on protein function. In depth re-analysis of light and electron microscopy specimens for 9 available kidney biopsies was conducted to identify pathological features and correlates of TRPC6-AP. Large-scale sequencing data did not support causality for TRPC6 protein-truncating variants. We identified 21 unique TRPC6 missense variants, clustering in three distinct regions of the protein, and with different effects on TRPC6 3D protein structure. Kidney biopsy analysis revealed FSGS patterns of injury in most cases, along with distinctive podocyte features including diffuse foot process effacement and swollen cell bodies. The majority of patients presented in adolescence or early adulthood but with ample variation (average 22, SD ± 14 years), with frequent progression to kidney failure but with variability in time between presentation and ESKD. This study provides insights into the genetic spectrum, clinicopathological associations, and natural history of TRPC6-AP.

Genetic Structure and Phylogeographic Divergence of Thymallus brevicephalus in the Ob‐Irtysh River Headwaters

ABSTRACTClarifying the genetic structure and population history of a species can reveal the impacts of historical climate and geological changes, providing critical insights for developing effective conservation strategies for ecologically significant fish. The Markakol grayling (Thymallus brevicephalus), an endangered species found in the Altai‐Sayan Mountain region of Central Asia, serves as an ideal model for studying these factors. In this study, populations of a grayling (Thymallus) species discovered in the upper Irtysh River headwaters in Xinjiang, China, were analyzed to assess genetic diversity and population structure. Mitochondrial DNA sequences (cytochrome b and control region), along with 10 microsatellite markers, were used to examine genetic variation. Phylogenetic and genetic distance analyses confirmed the species, long misidentified as Arctic grayling (T. arcticus), as T. brevicephalus. This species can be divided into two distinct geographic groups: eastern and western, with the Crane River acting as the boundary. The divergence between these groups likely corresponds to refugia formed during the Pleistocene glaciation of the Altai Mountains, approximately 0.48 MA (million years ago) (range: 0.30 to 0.71 Ma). High haplotype diversity (Hd > 0.5) and low nucleotide diversity (π < 0.005) suggest that, despite the species' genetic richness, T. brevicephalus remains vulnerable to genetic drift, which could threaten its long‐term survival. This vulnerability may stem from inbreeding within small refugial populations during the glacial period, followed by gradual population expansion. Our study offers novel insights into grayling populations, with results that have direct implications for management by serving as a tool for the identification of conservation units.

Генетические портреты хантов и манси по гаплогруппам Y-хромосомы в контексте генофондов России

Khanty and Mansi are small indigenous peoples of Western Siberia with the unique cultural, anthropological, and linguistic characteristics. The study of their gene pool will make it possible to reconstruct the genetic structure of the Ugric-speaking population, of which in modern times only Khanty and Mansi remain, along with Hungarians, in whose gene pool there are traces of medieval migration of the Ugric-speaking Magyars. The detailed characterization of the gene pool of Khanty and Mansi is important for reconstruction of Ugric populations and genetic history of the region. The study was aimed to assess representative samples of Khants (n = 83) and Mansi (n = 74) based on the standard panel of 60 SNP markers and the extended panel of 74 Y-chromosomal SNP markers by statistical and cartographic methods in the context of indigenous population of Urals and Western Siberia. The differences between the gene pools of Khanty and Mansi have been revealed based on both standard panel of Y chromosome haplogroups and branches of haplogroups N2 and N3a4. Most of the Khanty gene pool is evenly distributed between N2-Y3195 (26%), N2-VL67 (23%), and N3a4-Z1936 (23%). The “Western” branch N2-Y3195 predominates in the Mansi gene pool (69%). Mansi gravitate towards populations of the Urals-Volga region in the multidimensional genetic space. Based on the standard panel of Y haplogroups, Khanty are close to the populations of Western and South Siberia. However, the analysis of branches N3a4 has shown that Khanty are intermediate between the “Uralic” and “Siberian” clusters: when the ancestors of Khanty moved from the Ural region to the northeast, these acquired both genetic components. The gene geographic maps of 10 haplogroup N3a4 branches in the populations of Urals and Western Siberia reflect the dynamic changes of the gene pool that took place 4–2 kya.

The maternal genetic history of tribal populations of Chhattisgarh, India

The central region of India boasts a rich tribal heritage and the highest number of tribal populations in the country. Analysing the genetic history of this population can offer valuable insights into various demographic processes that shaped the gene pool of present-day settlers of this region. In this study, we utilize a recently validated Next-generation sequencing (NGS) technique to sequence 24 tribal mitogenomes from the Chhattisgarh population for genetic ancestry and forensic analysis. The identified ancient haplogroups in this population can be traced back to the pre-Last Glacial Maximum (LGM) period. Our Bayesian analysis provides evidence for maternal ancestral expansion following the earliest Out-of-Africa migration, followed by a prolonged steady phase. We identified three basal founding haplogroups, M2, R5, and U2 in the Chhattisgarh region that diversified during the Neolithic period. Indistinct distribution pattern of these haplogroups among tribes and castes suggests that the maternal ancestry of Chhattisgarh population predates any kind of social stratification that exists today in the Indian subcontinent. Furthermore, our analysis suggests that this region remained unaffected by the Last Glacial Maximum. The forensic analysis of the mitogenomes demonstrates a high power of discrimination (0.9256) within the Chhattisgarh population, thus supporting the applicability of mitogenome NGS technology in forensic contexts.

Hereditary and clinical insights into paraganglioma and pheochromocytoma.

Approximately 30-40% of paragangliomas (PGLs) and pheochromocytomas (PCCs) harbor an underlying hereditary cause. Early identification of at-risk individuals is imperative given the early onset, aggressiveness of tumors, and other tumor/cancer risks associated with hereditary PGLs/PCCs. This study analyzes the clinical presentations and genetic histories of patients with PGL/PCC and/or hereditary risk to contribute to the expanding knowledge in this rare population. A retrospective chart review identified two cohorts of patients seen in cancer genetics clinics at an academic medical center and a safety-net hospital between August 2016 and December 2022. Cohort 1 consisted of patients with likely pathogenic variants (LPVs)/pathogenic variants (PVs) in hereditary PGL/PCC predisposition genes. Cohort 2 consisted of patients with a personal history of a PGL/PCC. Demographics, personal/family history, and genetic testing outcomes were analyzed. A total of 560 patients met the study criteria (Cohort 1, n = 364; Cohort 2, n = 269). In Cohort 1, 77 (21.1%) patients had an incidental LPV/PV in a PGL/PCC gene. Nearly half (n = 36, 46.8%) were in SDHx genes, with a majority in SDHA (n = 21). In Cohort 2, 86 patients tested positive for 87 LPV/PV in a hereditary cancer predisposition gene. The SDHx genes were most likely to have an LPV/PV identified (SDHB n = 24, SDHD n = 23). Multigene panels identify patients at risk for hereditary PGL/PCC, many of whom are incidentally found. While SDHA LPV/PVs were the most frequent incidental finding, they were less common in patients with PGL/PCC, indicating the need for longitudinal studies to better understand the prevalence and penetrance of these tumors.

Abstract A147: A ten-year overview of cancer genetic family history screening in Georgia’s Latina population

Abstract Introduction: Population-based cancer genetic family history screening to identify families at high risk for BRCA-associated cancers has been endorsed by national public health policies. This report aimed to describe the utilization of family history screening services from 2013 to 2022 according to rurality and socioeconomic deprivation among the Latina community in the state of Georgia. Methods: Self-identified Latina women who attended a medical appointment at participating Georgia Public Health Clinics were invited to utilize the cancer genetic family history screening services. Screening results and participant zip code were reviewed. Area deprivation index (ADI) was measured at the census block group level and assessed as a dichotomous variable (more deprived and less deprived). Rurality was measured through Rural-Urban Commuting Area (RUCA) codes and was assessed dichotomously (urban and rural). The ADI and RUCA codes were linked to participant data by zip code to characterize genetic service access among the Latina community. Results: We found 9,330 (3.31%) adult Latinas in Georgia completed cancer genetic family history screening from 2013-2022. In this sample, 9,066 (97.17%) women screened negative, and 264 (2.83%) women screened positive (i.e., family history suggestive of higher risk for carrying BRCA1/2 mutations compared to the general population). The family history screening program reached Latinas in 16 of 18 public health districts in Georgia. However, family history screening completion varied significantly across the 16 districts (mean=327 women, range: 2 - 1,337). FH screening completion was higher among Latinas in urban areas (n=7,871) than Latinas in rural areas (n=1,459). Latinas who lived in more socially deprived areas appeared to have a higher number of screening completion (n=5,207) than those living in less socially deprived areas (n=4,123) due to interaction with urbanicity. Conclusions: Georgia’s family history screening program was able to reach Latina women across the state of Georgia, particularly those living in urban, socially deprived areas. To ensure equitable cancer genetic screening dissemination, future efforts should prioritize tailored outreach in rural regions and a comprehensive evaluation to identify key determinants of screening trends among Georgia’s Latina population. Citation Format: Dayanna A. Ramírez León, Lauren E. Barber, Sheryl Gabram-Mendola, Cindy Snyder, Susan Vadaparampil, Lindsay Fuzzell, Lauren E. McCullough, Lynn Durham, Yue Guan. A ten-year overview of cancer genetic family history screening in Georgia’s Latina population [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A147.

Genetic history and biological adaptive landscape of the Tujia people inferred from shared haplotypes and alleles

BackgroundHigh-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent.ObjectivesThis study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin.ResultsPopulation genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture.ConclusionsThe study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.