Genetic History Research Articles

Family History of Age-Related Macular Degeneration and Genetics Predict Progression to Advanced Age-Related Macular Degeneration Adjusting for Macular Status, Demographic, and Lifestyle Factors

To determine if a family history of age-related macular degeneration (AMD) and genetic variants identify eyes at higher risk for progression to advanced AMD (AAMD), after controlling for baseline demographics, behavioral factors, and macular status. Prospective, longitudinal cohort study. Eyes were classified using the Age-Related Eye Disease Study severity scale. Non-genetic and genetic predictors for progression to AAMD, geographic atrophy, and neovascular disease were evaluated. Cox proportional hazards models using the eye as the unit of analysis were used to calculate hazard ratios (HRs), accounting for correlated data. Discrimination between progressing and non-progressing eyes was assessed using C-statistics and net reclassification improvement (NRI). Among 4910 eyes, 863 progressed to AAMD over 12 years. Baseline AMD severity scale and status of the fellow eye were important predictors; genes provided additional discrimination. A family history of AMD also independently predicted progression after accounting for genetic and other covariates: 1 family member versus none (HR 1.21 [95% confidence interval {CI} 1.02-1.43]; P=0.03); ≥2 family members versus none (HR 1.55 [95% CI 1.26-1.90]; P < 0.001). A composite risk score calculated using β estimates of both non-genetic and significant genetic factors predicted progression to AAMD (HR 5.57; 90th vs 10th percentile; area under the receiver operating characteristic curve [AUC] = 0.92), providing superior fit compared with other models, including one with only ocular variables (NRI=0.34; P < 0.001; AUC = 0.87, ΔAUC 0.05 ± 0.005; P < 0.001). Genetic variants and family history provided additional discrimination for predicting progression to AAMD, after accounting for baseline macular status and other covariates.

Tracing genetic variation of Gelidium canariense (Rhodophyta) based on new and historical collections

ABSTRACT Genetic sequencing of herbarium specimens provides invaluable information on species genetic history. However, several factors hinder the extraction of high-quality DNA from long-term preserved specimens. Our goal was to study the genetic variability of the endemic and habitat-forming macroalga Gelidium canariense over the last 40 years using the mitochondrial intergenic marker cox2-3 spacer. We also studied the genetic diversity at the mesoscale (<100 km), i.e. between two localities on the north coast of Tenerife and at the macroscale (>100 km) using specimens collected on the island of La Palma. We found the presence of the same haplotype at the same location for the last 40 years. This haplotype also coincided within populations of Puerto de la Cruz and Garachico (Tenerife Island) and between populations of different islands (Tenerife and La Palma). This study provides a baseline (i.e. extraction method, PCR protocol for cox2-3 spacer molecular marker, level of DNA degradation of herbarium samples) of the genetic characterization of G. canariense that can be used in future molecular studies to better understand the distribution of genetic diversity in this vulnerable species.

Common Treatment Formulation for Non-Scaring (Androgenetic) Alopecia

In spite of being a non-life-threatening condition, hair loss (alopecia) severely impacts the quality of life of individuals who experience it. Recent studies indicate that the number of patients suffering from alopecia globally is on the rise. Androgenic alopecia (AGA) affects both genders at all ages. Genetic factors and family history are found to greatly impact the likelihood of experiencing hair loss. Statistics reveal that during the course of their lives, 80% of men experience alopecia, while 40 to 50% of women are likely to face some form of hair shedding. AGA is characterized by frontal-temporal hair shedding in men and hair thinning of the midline part of the scalp for women. A variety of herbal formulations are available on the market to combat AGA, while only two FDA-approved medications exist at the moment: oral finasteride and topical minoxidil. Topical formulations of finasteride are still under clinical trials. Minoxidil and finasteride formulations provide effective AGA treatment for both genders. Recent concerns regarding potential side effects of these two medications have drawn interest in providing new innovative alternative formulations (nutrients, minerals and vitamins) to provide a safer treatment against AGA. This article provides a brief overview of the current and alternative AGA formulations.

Metabolic Syndrome among Female School Teachers: A Sedentary Occupational Sector.

Dyslipidemia, insulin resistance, hypertension, and abdominal obesity are important determinants of metabolic syndrome (MetS). Ample studies provide statistical data on the prevalence of MetS among the general public. Conversely, there is a paucity of data on the risk of MetS among different sedentary occupational groups. To assess the risk of MetS among female school teachers and to identify factors contributing to MetS. The study was conducted among 256 female school teachers residing in Chennai city. A questionnaire was used to elicit information on the socio-demographic profile, diet pattern, physical fitness, and genetic history of lifestyle diseases. Anthropometric, biochemical, and clinical parameters were measured using standard methods. MetS was diagnosed using the harmonizing definition. Data analysis was done using Statistical Package for Social Sciences software. Results evince that 39.45% of female school teachers were diagnosed with MetS, of which 26.56% had three components, 9.77% had four components, and 3.12% had all components of MetS. Abdominal obesity (99%) and low levels of high-density lipoprotein cholesterol (HDL-C) (96.04%) were the most predominant components. The least common component was diastolic hypertension (32.67%). MetS components were high among school teachers aged 36-45 years and 46-55 years. Age, fasting hyperglycemia, paternal history of hypertension, physical inactivity, eating out, and consumption of refined cereals significantly contributed to MetS (P < 0.05). Results highlight the need to identify high-risk individuals and promote a healthy lifestyle through various intervention programs.

Unpacking the Factors of Overweight/Obesity in Type 2 Diabetes: What You Need to Know: Review Article

The rising prevalence of overweight and obesity among type 2 diabetic patients has become a major concern for healthcare professionals. Obesity and overweight are significant risk factors for the development of type 2 diabetes. In fact, it is estimated that over 90% of individuals with type 2 diabetes are either overweight or obese. Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, leading the World Health Organization to label them as pandemics of the 21st century. In this article, we will explore the different factors that contribute to overweight/obesity among individuals with type 2 diabetes. Genetics and family history play a crucial role in the development of obesity. Lifestyle factors, such as poor dietary habits, physical inactivity, sedentary behavior and poor sleep quality and duration are also a significant risk factor for obesity.

CERKL-Associated Retinal Dystrophy: Genetics, Phenotype, and Natural History

To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date. Multicenter retrospective cohort study. Forty-seven patients (37 families) with likely disease-causing CERKL variants. Review of clinical notes, ophthalmic images, and molecular diagnosis from 2 international centers. Visual function, retinal imaging, and characteristics were evaluated and correlated. The mean age at the first visit was 29.6± 13.9 years, and the mean follow-up time was 9.1± 7.4 years. The most frequent initial symptom was central vision loss (40%), and the most common retinal feature was well-demarcated areas of macular atrophy (57%). Seventy-seven percent of the participants had double-null genotypes, and 64% had electrophysiological assessment. Among the latter, 53% showed similar severity of rod and cone dysfunction, 27% revealed a rod-cone, 10% a cone-rod, and 10% a macular dystrophy dysfunction pattern. Patients without double-null genotypes tended to have fewer pigment deposits and included a higher proportion of older patients with a relatively mild electrophysiological phenotype. Longitudinal analysis showed that over half of the cohort lost 15 ETDRS letters or more in ≥ 1 eye during the first 5 years of follow-up. The phenotype of CERKL-retinal dystrophy is broad, encompassing isolated macular disease to severe retina-wide involvement, with a range of functional phenotypes, generally not fitting in the rod-cone/cone-rod dichotomy. Disease onset is often earlier, with more severe retinal degenerative changes and photoreceptor dysfunction, in nullizygous cases. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Inferring the population history of Kyrgyz in Xinjiang, Northwest China from genome-wide array genotyping.

Xinjiang plays a vital role in the trans-Eurasian population migration, language diffusion, and culture and technology exchange. However, the underrepresentation of Xinjiang's genomes has hindered a more comprehensive understanding of Xinjiang's genetic structure and population history. We collected and genotyped 70 southern Xinjiang's Kyrgyz (SXJK) individuals and combined the data with modern and ancient Eurasians published. We used allele-frequency methods, including PCA, ADMIXTURE, f-statistics, qpWave/qpAdm, ALDER, Treemix, and haplotype-shared methods including shared-IBD segments, fineSTRUCTURE, and GLOBETROTTER to unveil the fine-scale population structure and reconstruct admixture history. We identified genetic substructure within the SXJK population with subgroups showing different genetic affinities to West and East Eurasians. All SXJK subgroups were suggested to have close genetic relationships with surrounding Turkic-speaking groups that is, Uyghur, Kyrgyz from north Xinjiang and Tajikistan, and Chinese Kazakh, suggesting a shared ancestry among those populations. Outgroup-f3 and symmetrical f4 statistics showed a high genetic affinity of SXJK to present-day Tungusic, Mongolic-speaking populations and Ancient Northeast Asian (ANA) related groups. Allele sharing and haplotype sharing profiles revealed the east-west admixture pattern of SXJK. The qpAdm-based admixture models showed that SXJK derived ancestry from East Eurasian (ANA and East Asian, 42.7%-83.3%) and West Eurasian (Western Steppe herders and Central Asian, 16.7%-57.3%), the recent east-west admixture event could be traced to 1000 years ago based on ALDER and GLOBETROTTER analysis. The high genetic affinity of SXJK to present-day Tungusic and Mongolic-speaking populations and short-shared IBD segments indicated their shared common ancestry. SXJK harbored a close genetic affinity to ANA-related populations, indicating the Northeast Asian origin of SXJK. The West and East Eurasian admixture models observed in SXJK further provided evidence of the dynamic admixture history in Xinjiang. The east-west admixture pattern and the identified ancestral makeup of SXJK suggested a genetic continuity from some Iron Age Xinjiang populations to present-day SXJK.

Cause of Seamless Integration

&#x0D; &#x0D; &#x0D; This paper revisits the longstanding tradition concerning the dual authorship of the Light on Literature (Kāvyaprakāśa), the dominant treatise on Sanskrit poetics in the second millennium CE. The discussion focuses on one case study, a brief comment dismissing the ornament “cause” (hetu), found in the latter part of chapter 10 in the portion traditionally attributed to Mammaṭa’s successor Allaṭa (aka Alaka). This passage is analyzed in the broader context of the Light’s discussion of semantic capacities (chapter 2), suggestion (chapter 4), and other ornaments (chapter 10). The essay also looks at the way generations of commentators have dealt with this topic and the potential inconsistencies in its treatment in the Light. The paper thus throws light on the question of the work’s overall integration, seamless or not so seamless, both in its genetic and receptive histories.&#x0D; &#x0D; &#x0D;

Unpacking the Factors of Overweight/Obesity in Type 2 Diabetes: What You Need to Know: Review Article

The rising prevalence of overweight and obesity among type 2 diabetic patients has become a major concern for healthcare professionals. Obesity and overweight are significant risk factors for the development of type 2 diabetes. In fact, it is estimated that over 90% of individuals with type 2 diabetes are either overweight or obese. Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, leading the World Health Organization to label them as pandemics of the 21st century. In this article, we will explore the different factors that contribute to overweight/obesity among individuals with type 2 diabetes. Genetics and family history play a crucial role in the development of obesity. Lifestyle factors, such as poor dietary habits, physical inactivity, sedentary behavior and poor sleep quality and duration are also a significant risk factor for obesity.

Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants.

Charcot-Marie-Tooth disease (CMT) due to GJB1 variants (CMTX1) is the second most common form of CMT. It is an X-linked disorder characterized by progressive sensory and motor neuropathy with males affected more severely than females. Many reported GJB1 variants remain classified as variants of uncertain significance (VUS). In this large, international, multicentre study we prospectively collected demographic, clinical and genetic data on patients with CMT associated with GJB1 variants. Pathogenicity for each variant was defined using adapted American College of Medical Genetics criteria. Baseline and longitudinal analyses were conducted to study genotype-phenotype correlations, to calculate longitudinal change using the CMT Examination Score (CMTES), to compare males versus females, and pathogenic/likely pathogenic (P/LP) variants versus VUS. We present 387 patients from 295 families harbouring 154 variants in GJB1. Of these, 319 patients (82.4%) were deemed to have P/LP variants, 65 had VUS (16.8%) and three benign variants (0.8%; excluded from analysis); an increased proportion of patients with P/LP variants compared with using ClinVar's classification (74.6%). Male patients (166/319, 52.0%, P/LP only) were more severely affected at baseline. Baseline measures in patients with P/LP variants and VUS showed no significant differences, and regression analysis suggested the disease groups were near identical at baseline. Genotype-phenotype analysis suggested c.-17G>A produces the most severe phenotype of the five most common variants, and missense variants in the intracellular domain are less severe than other domains. Progression of disease was seen with increasing CMTES over time up to 8 years follow-up. Standard response mean (SRM), a measure of outcome responsiveness, peaked at 3 years with moderate responsiveness [change in CMTES (ΔCMTES) = 1.3 ± 2.6, P = 0.00016, SRM = 0.50]. Males and females progressed similarly up to 8 years, but baseline regression analysis suggested that over a longer period, females progress more slowly. Progression was most pronounced for mild phenotypes (CMTES = 0-7; 3-year ΔCMTES = 2.3 ± 2.5, P = 0.001, SRM = 0.90). Enhanced variant interpretation has yielded an increased proportion of GJB1 variants classified as P/LP and will aid future variant interpretation in this gene. Baseline and longitudinal analysis of this large cohort of CMTX1 patients describes the natural history of the disease including the rate of progression; CMTES showed moderate responsiveness for the whole group at 3 years and higher responsiveness for the mild group at 3, 4 and 5 years. These results have implications for patient selection for upcoming clinical trials.

Population History Shapes Responses to Different Temperature Regimes in Drosophila subobscura.

Drosophila subobscura is considered a good model species for investigation of a population's ability to adapt and cope with climate changes. Decade long research has shown that inversion frequencies change in response to environmental factors indicating their role in adaptation to novel environments. The mechanisms behind organisms' responses to temperature are complex, involving changes in physiology, behavior, gene expression and regulation. On the other hand, a population's ability to respond to suboptimal conditions depends on standing genetic variation and population history. In order to elucidate the role of local adaptation in population response to the changing temperature, we investigated the response to temperature in D. subobscura individuals originating from two different altitudes by combining traditional cytogenetic techniques with assessing the levels of Hsp70 protein expression. Inversion polymorphism was assessed in the flies sampled from natural populations and in flies reared in laboratory conditions at three different temperatures after five and sixteen generations and Hsp70 protein expression profile in 12th generation flies at the basal level and after heat shock induction. Our results indicate that local adaptation and population history influence population response to the changing temperature.

The genetic history of the Southern Andes from present-day Mapuche ancestry

The southernmost regions of South America harbor some of the earliest evidence of human presence in the Americas. However, connections with the rest of the continent and the contextualization of present-day indigenous ancestries remain poorly resolved. In this study, we analyze the genetic ancestry of one of the largest indigenous groups in South America: the Mapuche. We generate genome-wide data from 64 participants from three Mapuche populations in Southern Chile: Pehuenche, Lafkenche, and Huilliche. Broadly, we describe three main ancestry blocks with a common origin, which characterize the Southern Cone, the Central Andes, and Amazonia. Within the Southern Cone, ancestors of the Mapuche lineages differentiated from those of the Far South during the Middle Holocene and did not experience further migration waves from the north. We find that the deep genetic split between the Central and Southern Andes is followed by instances of gene flow, which may have accompanied the southward spread of cultural traits from the Central Andes, including crops and loanwords from Quechua into Mapudungun (the language of the Mapuche). Finally, we report close genetic relatedness between the three populations analyzed, with the Huilliche characterized additionally by intense recent exchanges with the Far South. Our findings add new perspectives on the genetic (pre)history of South America, from the first settlement through to the present-day indigenous presence.Follow-up fieldwork took these results back to the indigenous communities to contextualize the genetic narrative alongside indigenous knowledge and perspectives. VIDEO ABSTRACT.

Rare Epithelial Ovarian Cancers: Low Grade Serous and Mucinous Carcinomas.

The ovarian epithelial cancer histotypes can be divided into common and rare types. Common types include high-grade serous ovarian carcinomas and the endometriosis-associated cancers, endometrioid and clear-cell carcinomas. The less common histotypes are mucinous and low-grade serous, each comprising less than 10% of all epithelial carcinomas. Although histologically and epidemiologically distinct from each other, these histotypes share some genetic and natural history features that distinguish them from the more common types. In this review, we will consider the similarities and differences of these rare histological types, and the clinical challenges they pose.

Genetic admixture history of the Aisin Gioro family in Northeast China inferred from genome-wide genotyping

Genetic admixture history of the Aisin Gioro family in Northeast China inferred from genome-wide genotyping

Barriers to chimpanzee gene flow at the south-east edge of their distribution.

Populations on the edge of a species' distribution may represent an important source of adaptive diversity, yet these populations tend to be more fragmented and are more likely to be geographically isolated. Lack of genetic exchanges between such populations, due to barriers to animal movement, can not only compromise adaptive potential but also lead to the fixation of deleterious alleles. The south-eastern edge of chimpanzee distribution is particularly fragmented, and conflicting hypotheses have been proposed about population connectivity and viability. To address this uncertainty, we generated both mitochondrial and MiSeq-based microsatellite genotypes for 290 individuals ranging across western Tanzania. While shared mitochondrial haplotypes confirmed historical gene flow, our microsatellite analyses revealed two distinct clusters, suggesting two populations currently isolated from one another. However, we found evidence of high levels of gene flow maintained within each of these clusters, one of which covers an 18,000 km2 ecosystem. Landscape genetic analyses confirmed the presence of barriers to gene flow with rivers and bare habitats highly restricting chimpanzee movement. Our study demonstrates how advances in sequencing technologies, combined with the development of landscape genetics approaches, can resolve ambiguities in the genetic history of critical populations and better inform conservation efforts of endangered species.

Investigation on psychological status of patients with cervical precancerous lesions and cancer among Han and Ethnic minority in Yunnan Province of China

ObjectiveThe aim of this study was to explore the correlation and difference of influencing factors by analyzing the psychological status of patients with cervical precancerous lesions and cancer in Han and Ethnic minorities. So as to provide evidence for more targeted psychological intervention for categories types of patients. MethodsThe Chinese version of Kessler 10 scale was used to investigate 200 Han Chinese patients with cervical lesions and 100 ethnic minority patients with cervical lesions in Yunnan Cancer Center. Statistical analysis was performed using t-test, analysis of variance, and multivariable linear regression. ResultsThere was no significant difference in the distribution of demographic characteristics between the two groups (P > 0.05).The results of univariate analysis showed that the impression of K10 score was statistically significant among the following factors: educational level, awareness of HPV vaccine, disease screening status, employee medical insurance, economic burden of disease, cancerous or not, pathological type, treatment modalities, marital status, and family genetic history of tumor (P < 0.05). After multivariate analysis and considering the influence of the number of independent variables, it indicates that the economic burden of the disease, occupation, and family genetic history of tumor had a greater impact on the total score of Han patients among many factors, accounting for a total of 8.1%(Adj R2 = 0.081).Treatment modalities had the greatest effect on the scores of ethnic minority patients, accounting for 8.4%(Adj R2 = 0.084). ConclusionThe factors affecting the psychological status of patients between the two groups have similarities and differences. Multifactorial analysis showed that the main factors affecting the psychology of Han patients were: economic burden caused by the disease, occupation, and family genetic history of tumor; while the main factors affecting the psychology of minority patients were: treatment modalities. Therefore, targeted recommendations and policy measures can be proposed respectively.

Analysis of Ovary Cancer in the Gynecology Room

Ovarian cancer is the most common cancer in Indonesian women, with an incidence rate of 14,896 cases in 2020 and a mortality rate of 9,581 cases. According to data from Global Cancer Incidence, Mortality and Prevalence (Globocan), ovarian cancer is the most common cancer among Indonesian women, with an incidence rate of 14,896 cases in 2020 and a mortality rate of 9,581 cases. To determine the factors that influence the incidence of ovarian cancer in patients in the Gynecology Room of the Gatot Soebroto Army Hospital in 2022. Methods: This research is a quantitative study with a case-control design, using primary data with a sample of 54 patients on the 2nd floor of the Gynecology Room. The sampling technique used random sampling. Data analysis using univariate and bivariate using chi square. Research Results: 27 respondents (50%) had ovarian cancer. Variables related to the incidence of ovarian cancer were genetic history (0.000), history of contraception (0.001) and smoking history (0.005) while variables that were not related were obesity (0.268) and age of menarche (776). there is a relationship between genetic history, contraceptive history and smoking history with the incidence of ovarian cancer. It is hoped that women will increase their knowledge about the factors that influence the incidence of ovarian cancer and adopt a healthy lifestyle in their daily activities.

English

Faba bean is an important grain legume crop in the world. Use of plant genetic breeding resources can help develop high yield and stress tolerant plant genotypes. In this study, genetic diversity of 144 faba bean accessions, collected from different parts of the world growing under Saudi Arabian conditions, was evaluated based on agro morphological basis. A wide range of variability was recorded for all the qualitative characters except growth habit (determinate 1.3% indeterminate 98.7%) and pod shattering (non-shattering 99.4%; shattering 0.6%). A high level of diversity was recorded in the qualitative characteristics including leaflet size, stipule spot pigmentation, flower ground color, intensity of streak, wing petal colors, pod colors, pod angle, hilum color, pod shattering, ground color of testa and seed shape in the tested faba bean accessions. The principal component analysis results showed that highest (95.32%) diversity came from three principal components, and dendrogram results divided faba bean into 8 distinct groups based on their origin. The cluster study of the tested faba beans accessions was based on the origin as well as on the genetic history. The extent of variability and diversity in the tested faba bean accessions indicate their potential for use in the faba bean breeding program.

Severe respiratory viral infections: T-cell functions diverging from immunity to inflammation.

Respiratory viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) trigger distinct clinical outcomes defined by immunity-based viral clearance or disease associated with exaggerated and prolonged inflammation. The important role of T cells in shaping both antiviral immunity and inflammation has revived interest in understanding the host-pathogen interactions that lead to the diverse functions of T cells in respiratory viral infections. Inborn deficiencies and acquired insufficiency in immunity can prolong infection and shift the immune response towards exacerbated inflammation, which results from persistent innate immune activation and bystander T-cell activation that is nonspecific to the pathogen but is often driven by cytokines. This review discusses how virus variants, exposure doses, routes of infection, host genetics, and immune history can modulate the activation and function of T cells, thus influencing clinical outcomes. Knowledge of virus-host interaction can inform strategies to prevent immune dysfunction in respiratory viral infection and help in the treatment of associated diseases.

Population genetic assessment of Viburnum japonicum in China using ddRAD-seq.

Viburnum japonicum is a rare plant species and endemic to the coastal region of Eastern Asia with extremely small populations. Within mainland China, this species can be only found in narrow habitats of the northeast coastal islands of Zhejiang Province. However, there are scarce conservation genetic studies on V. japonicum, which has limited the effective conservation and management of this rare species. Here, 51 individuals in four natural populations covering the Chinese geographic range of the species were sampled to assess the genetic diversity and population structure. A total of 445,060 high-quality single nucleotide polymorphisms (SNPs) were identified using double digest restriction-site associated sequencing (ddRAD-seq). The overall average values of observed heterozygosity (Ho), expected heterozygosity (He), and average nucleotide diversity (π), were 0.2207, 0.2595, and 0.2741, respectively. The DFS-2 population exhibited the highest level of genetic diversity among all the populations. Genetic differentiation between populations was moderate (F ST = 0.1425), and there was selfing between populations (F IS = 0.1390, S = 24.52%). Of the total genetic variation, 52.9% was found among populations through AMOVA analysis. The Mantel test (r = 0.982, p = 0.030) combined with analyses of the Maximum Likelihood (ML) phylogenetic tree, ADMIXTURE, and principal component analysis (PCA), revealed that populations of V. japonicum were genetically segregated and significantly correlated with their geographical distribution. Our study demonstrated that V. japonicum maintained a medium level of genetic diversity and differentiation with a strong population structure, and the results were mainly affected by its island distribution pattern and self-crossing characteristics. These results provide insights into the genetic diversity and population history of V. japonicum, critical information for conserving and sustainably developing its genetic resources.