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Genetic factors play a fundamental role in disease development. Studying the genetic association with clinical outcomes is critical for understanding disease biology and devising novel treatment targets. However, the frequencies of genetic variations are often low, making it difficult to examine the variants one-by-one. Moreover, the clinical outcomes are complex, including patients' survival time and other binary or continuous outcomes such as recurrences and lymph node count, and how to effectively analyze genetic association with these outcomes remains unclear. In this article, we proposed a structured test statistic for testing genetic association with mixed types of survival, binary, and continuous outcomes. The structured testing incorporates known biological information of variants while allowing for their heterogeneous effects and is a powerful strategy for analyzing infrequent genetic factors. Simulation studies show that the proposed test statistic has correct type I error and is highly effective in detecting significant genetic variants. We applied our approach to a uterine corpus endometrial carcinoma study and identified several genetic pathways associated with the clinical outcomes.
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The present study investigated two single nucleotide polymorphisms (SNPs)-rs479200 and rs516651 in the host EGLN1/PHD2 gene for their association with COVID-19 severity. A retrospective cohort of 158 COVID-19 patients from the Indian population (March 2020 to June 2021) was enrolled. Notably, the frequency of C allele (0.664) was twofold higher than T allele (0.336) in severe COVID-19 patients. Here, we report a novel finding that the C allele of rs479200 in the EGLN1 gene imparts a high risk of severe COVID-19 (odds ratio-6.214 (1.84-20.99) p = 0.003; 9.421 (2.019-43.957) p = 0.004), in additive inheritance model (adjusted and unadjusted, respectively).
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COVID-19 , Humanos , Alelos , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático , Predisposição Genética para Doença , Frequência do Gene , Prolina Dioxigenases do Fator Induzível por Hipóxia/genéticaRESUMO
Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (â¼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that â¼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.
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Testes Genéticos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Testes Genéticos/métodos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Glucosilceramidase/genética , alfa-Sinucleína/genética , Predisposição Genética para Doença , Ubiquitina-Proteína Ligases/genética , Estudos de Coortes , Proteínas Quinases/genética , Mutação , AdultoRESUMO
BACKGROUND: Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. FINDINGS: We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10-6). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (Pheterogeneity = 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated. CONCLUSIONS: The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.
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Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Pessoa de Meia-Idade , Estudo de Associação Genômica Ampla , Mama , Predisposição Genética para Doença , Estratificação de Risco Genético , Proteínas com Motivo Tripartido , Ubiquitina-Proteína LigasesRESUMO
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD)-related fibrosis is heritable, but it is unclear how family history may be used to identify first-degree relatives with advanced fibrosis. We aimed to develop and validate a simple risk score to identify first-degree relatives of probands who have undergone assessment of liver fibrosis who are at higher risk of NAFLD with advanced fibrosis. METHODS: This prospective, cross-sectional, familial study consisted of a derivation cohort from San Diego, California, and a validation cohort from Helsinki, Finland. This study included consecutive adult probands (n = 242) with NAFLD and advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 of their first-degree relatives. All included probands and first-degree relatives underwent evaluation of liver fibrosis, the majority by magnetic resonance elastography. RESULTS: A total of 396 first-degree relatives (64% male) were included. The median age and body mass index were 47 years (interquartile range, 32-62 y) and 27.6 kg/m2 (interquartile range, 24.1-32.5 kg/m2), respectively. Age (1 point), type 2 diabetes (1 point), obesity (2 points), and proband with NAFLD and advanced fibrosis (2 points) were predictors of advanced fibrosis among first-degree relatives in the derivation cohort (n = 220) and formed the NAFLD Familial Risk Score. The area under the receiver operator characteristic curve of the NAFLD Familial Risk Score for detecting advanced fibrosis was 0.94 in the validation cohort (n = 176). The NAFLD Familial Risk Score outperformed the Fibrosis-4 index in the validation cohort (area under the receiver operator characteristic curve, 0.94 vs 0.70; P = .02). CONCLUSIONS: The NAFLD Familial Risk Score is a simple and accurate clinical tool to identify advanced fibrosis in first-degree relatives. These data may have implications for surveillance in NAFLD.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos Transversais , Estudos Prospectivos , Fatores de Risco , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Predisposição Genética para Doença , Fígado/patologia , BiópsiaRESUMO
BACKGROUND: Previous research has found associations between various non-genetic factors and breast cancer (BrCa) risk. This study summarises and appraises the credibility of the available evidence on the association between non-genetic factors and BrCa risk. METHODS: We conducted an umbrella review of meta-analyses. Medline, Scopus, and the Cochrane databases were systematically searched for meta-analyses examining non-genetic factors and BrCa incidence or mortality. The strength of the evidence was graded in four categories (i.e., weak, suggestive, highly suggestive, convincing). RESULTS: A total of 781 meta-analyses from 280 publications were evaluated and graded. We included exposures related to anthropometric measurements, biomarkers, breast characteristics and diseases, diet and supplements, environment, exogenous hormones, lifestyle and social factors, medical history, medication, reproductive history, and pregnancy. The largest number of examined associations was found for the category of diet and supplements and for exposures such as aspirin use and active smoking. The statistically significant (P-value < 0.05) meta-analyses were 382 (49%), of which 204 (53.4%) reported factors associated with increased BrCa risk. Most of the statistically significant evidence (n = 224, 58.6%) was graded as weak. Convincing harmful associations with heightened BrCa risk were found for increased body mass index (BMI), BMI and weight gain in postmenopausal women, oral contraceptive use in premenopausal women, increased androstenedione, estradiol, estrone, and testosterone concentrations, high Breast Imaging Reporting and Data System (BIRADS) classification, and increased breast density. Convincing protective factors associated with lower BrCa risk included high fiber intake and high sex hormone binding globulin (SHBG) levels while highly suggestive protective factors included high 25 hydroxy vitamin D [25(OH)D] levels, adherence to healthy lifestyle, and moderate-vigorous physical activity. CONCLUSIONS: Our findings suggest some highly modifiable factors that protect from BrCa. Interestingly, while diet was the most studied exposure category, the related associations failed to reach higher levels of evidence, indicating the methodological limitations in the field. To improve the validity of these associations, future research should utilise more robust study designs and better exposure assessment techniques. Overall, our study provides knowledge that supports the development of evidence-based BrCa prevention recommendations and guidance, both at an individual level and for public health initiatives. TRIAL REGISTRATION: PROSPERO CRD42022370675.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/epidemiologia , Dieta , Suplementos Nutricionais , Estilo de Vida , Metanálise como Assunto , Fatores de RiscoRESUMO
INTRODUCTION: Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS: WWE registered at West China Hospital between January 2022 and October 2022 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded, and blood samples were collected for hormones, glucose metabolism testing, and whole-genome sequencing. RESULTS: After sample sequencing, quality control, and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS "burden score" of each individual were calculated to count the deleterious variants. A total of 95 WWE were included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The most commonly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, epoxysqualene biosynthesis signaling, and glutamate degradation signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In human gene connectome prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION: Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.
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Epilepsia , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , Epilepsia/epidemiologia , Epilepsia/genética , Glucose , China , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
PURPOSE OF REVIEW: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). RECENT FINDINGS: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.
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Transtornos de Enxaqueca , Transtornos do Sono-Vigília , Humanos , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Fatores Desencadeantes , Transtornos do Sono-Vigília/complicaçõesRESUMO
Clostridioides difficile infection (CDI), previously Clostridium difficile infection, is a symptomatic infection of the large intestine caused by the spore-forming anaerobic, gram-positive bacterium Clostridioides difficile. CDI is an important healthcare-associated disease worldwide, characterized by high levels of recurrence, morbidity, and mortality. CDI is observed at a higher rate in immunocompromised patients after antimicrobial therapy, with antibiotics disrupting the commensal microbiota and promoting C. difficile colonization of the gastrointestinal tract.A rise in clinical isolates resistant to multiple antibiotics and the reduced susceptibility to the most commonly used antibiotic molecules have made the treatment of CDI more complicated, allowing the persistence of C. difficile in the intestinal environment.Gut colonization and biofilm formation have been suggested to contribute to the pathogenesis and persistence of C. difficile. In fact, biofilm growth is considered as a serious threat because of the related antimicrobial tolerance that makes antibiotic therapy often ineffective. This is the reason why the involvement of C. difficile biofilm in the pathogenesis and recurrence of CDI is attracting more and more interest, and the mechanisms underlying biofilm formation of C. difficile as well as the role of biofilm in CDI are increasingly being studied by researchers in the field.Findings on C. difficile biofilm, possible implications in CDI pathogenesis and treatment, efficacy of currently available antibiotics in treating biofilm-forming C. difficile strains, and some antimicrobial alternatives under investigation will be discussed here.
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Antibacterianos , Biofilmes , Clostridioides difficile , Farmacorresistência Bacteriana , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologiaRESUMO
Atopic dermatitis (AD) is a chronic relapsing condition that is characterized by itching and redness of the skin. Our modern usage of atopic dermatitis dates back to 1933, when Wise and Sulzberger first coined the term to signify the disease's close association with other respiratory atopy, such as bronchial asthma and allergic rhinitis. A recent systematic review of 69 cross-sectional and cohort studies has confirmed that AD is now a worldwide phenomenon with lifetime AD prevalences of well over 20% in many affluent country settings. Although there is no obvious consistent overall global trend in the prevalence of AD, studies have shown that climate, urbanization, lifestyle, and socioeconomic class influence the prevalence of atopic dermatitis. Despite the pervasiveness of the disease, an understanding of atopic dermatitis has been hampered by a number of factors. Data suggests that extrinsic environmental factors work in concert with intrinsic immune mechanism and genetic factors to drive disease progression. With such a complex etiology, management of atopic dermatitis currently at best achieves symptomatic control rather than cure. This approach poses a significant burden on healthcare resources, as well as patients' quality of life. Current management methods of AD often involve a combination of non-pharmacologic modalities and prescription medications. Though they can be effective when employed, there are significant barriers to treatment for patients including time, costs, and medication side effects. Our aim, throughout this text, is to explore the complexities of AD, providing the healthcare provider with tips and tricks to improve patient care and satisfaction and the most current trends and treatment approaches on the horizon.
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Dermatite Atópica , Humanos , Dermatite Atópica/epidemiologia , Prevalência , Qualidade de Vida , Fatores de RiscoRESUMO
The aim of this study was to analyze the effects of non-genetic factors on the estimation of genetic parameters of early growth traits in hybrid mutton sheep using ASReml software, in order to provide theoretical basis for screening the optimal hybriding combinations and accelerating the breeding process of new breeds of specialized housed-feeding mutton sheep. We selected the wellgrown hybrid Southhu (Southdown × Hu sheep) and Dorhu (Dorset × Hu sheep) sheep as the research objects, constructed weight correction formulae for SH and DH sheep at 60 and 180 days; and used ASReml software to investigate the effects of non-genetic factors on the estimation of genetic parameters of early growth traits in hybrid sheep. The results showed that the birth month and birth type were found significant for all traits (p < 0.001); the heritability of maternal effects ranged from 0.0709 to 0.1859. It was found that both SH and DH sheep emerged the potential for rapid early growth and development, early growth traits are significantly affected by maternal genetic effects, thereby the maternal effect should be taken into consideration for the purpose of improving accuracy in parameter estimations and therefore increasing the success of breeding programs.
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Cruzamento , Animais , Ovinos/genética , Feminino , Hibridização Genética/genética , Software , Masculino , Peso Corporal/genética , Carneiro Doméstico/genética , Carneiro Doméstico/crescimento & desenvolvimento , Carneiro Doméstico/fisiologiaRESUMO
INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear. METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations. RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654). DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation. HIGHLIGHTS: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet was significantly associated with higher volumes and larger gray matter volumes in certain brain regions in UK adults, and the associations were not modified by genetic factors. No significant associations were observed between MIND diet and longitudinal changes in the investigated brain structural markers over a median of 2.2 years. Higher MIND score was significantly associated with slower atrophy in the putamen and pallidum among APOE ε4 non-carriers.
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Doença de Alzheimer , Dieta Mediterrânea , Adulto , Humanos , Apolipoproteína E4 , Doença de Alzheimer/genética , Substância Cinzenta , AtrofiaRESUMO
The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.
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Cardiopatias Congênitas , Coração , Humanos , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/etiologia , Animais , Coração/embriologia , Coração/crescimento & desenvolvimento , Crista Neural , Morfogênese , OrganogêneseRESUMO
Thrombosis is a multifaceted process involving various molecular components, including the coagulation cascade, platelet activation, platelet-endothelial interaction, anticoagulant signaling pathways, inflammatory mediators, genetic factors and the involvement of various cells such as endothelial cells, platelets and leukocytes. A comprehensive understanding of the molecular signaling pathways and cell interactions that play a role in thrombosis is essential for the development of precise therapeutic strategies for the treatment and prevention of thrombotic diseases. Ongoing research in this field is constantly uncovering new molecular players and pathways that offer opportunities for more precise interventions in the clinical setting. These molecular insights into thrombosis form the basis for the development of targeted therapeutic approaches for the treatment and prevention of thrombotic disease. The aim of this review is to provide an overview of the pathogenesis of thrombosis and to explore new therapeutic options.
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Células Endoteliais , Trombose , Humanos , Coagulação Sanguínea , Anticoagulantes , PlaquetasRESUMO
Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.
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Degeneração Macular , Humanos , Degeneração Macular/genética , Degeneração Macular/etiologia , Fatores de Risco , Predisposição Genética para Doença , Metais Pesados/toxicidade , Metais Pesados/efeitos adversos , Exposição Ambiental/efeitos adversos , ImunogenéticaRESUMO
The present study was aimed to evaluate the influence of non-genetic factors on several first lactation and lifetime performance traits and elucidate their genetic parameters in an organized Vrindavani cattle population. Data on eight first-lactation and thirteen lifetime traits were collected on 2400 cows with pedigree records that were reared during 33-year period (1989-2021). The first-lactation traits included age at first calving (AFC), total milk yield (FTMY), standard milk yield (FSMY305), peak yield (FPY), lactation length (FLL), dry period (FDP), service period (FSP) and calving interval (FCI). Whereas, the lifetime traits mainly included total lifetime milk yield (TLMY), total standard milk yield (TSMY), number of lactations completed (NL), total lactation length (TLL), herd life (HL), productive life (PL), average milk yield per day of herd life (TLMY/HL), average milk yield per day of productive life (TLMY/PL), average milk yield per day of productive life (TLMY/TLL). Other lifetime production traits included average service period (ASP), average dry period (ADP), average calving interval (ACI) and unproductive days (UD). The heritability estimates of first-lactation traits ranged between 0.026 and 0.228 and were found to be low for AFC (0.180 ± 0.042), FCI (0.191 ± 0.125), FSMY305 (0.145 ± 0.061), FTMY (0.165 ± 0.048), FDP (0.052 ± 0.049) and FSP (0.026 ± 0.033); however, FLL (0.229 ± 0.044) and FPY (0.202 ± 0.046) showed moderate heritability. Positive phenotypic correlation (p < 0.001) was revealed among FTMY, TLMY, TLL, HL and PL. The AFC produced a significant effect (p < 0.05) on several traits i,e, TLL, TLMY/HL, FSMY305, FPY, TLMY, HL and TLMY/PL. Lower AFC was associated with higher TLMY, TLL and TLMY/HL; while FSMY305, FPY, HL and TLMY/PL were higher in heifers that calved late in their life. The results revealed that AFC may be optimized with first lactation and lifetime traits for this population.
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Lactação , Leite , Bovinos/genética , Animais , Feminino , Lactação/genética , FenótipoRESUMO
Mithun (Bos frontalis), a domestically raised herbivore, holds significant economic importance for the farming community of Northeast India. This study aimed to elucidate the genetic parameters governing Mithun body weight traits across different ages using data from the sole organized semi-intensive Mithun farm in India. Information was gathered from 110 Mithuns born over a period spanning from 2011 to 2022. Body weight taken at week 1 (W1), 1-month (M1), 3-months (M3), 6-months (M6), 9-months (M9), 12-months (M12), 30-months (M30) and 45-months (M45) were considered for the study. The genetic parameters estimation employed the BLUPF90 suite of programs, incorporating univariate Gibbs sampler animal model with fixed effects; season and period of birth, and sex of the animal. Variance and covariance components, including direct additive genetic effects, were estimated. Heritability estimates for the eight body weight traits ranged from 0.47 ± 0.0050 to 0.50 ± 0.0043, indicating varying genetic influence across growth stages. Results revealed that Mithun herd has a substantial genetic variability for growth traits and therefore there is ample scope to select for a better growth rate. Here, we conclude that Month 12 (M12) and Month 9 (M9) body weights exhibit higher heritability, indicating potential for genetic improvement through selective breeding.
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Peso Corporal , Animais , Masculino , Feminino , Índia , Modelos Animais , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Bovinos/fisiologia , Variação GenéticaRESUMO
Breast cancer remains a significant contributor to morbidity and mortality within oncology. Risk factors, encompassing genetic and environmental influences, significantly contribute to its prevalence. While germline mutations, notably within the BRCA genes, are commonly associated with heightened breast cancer risk, a spectrum of other variants exists among affected individuals. Diagnosis relies on imaging techniques, biopsies, biomarkers, and genetic testing, facilitating personalised risk assessment through specific scoring systems. Breast cancer screening programs employing mammography and other imaging modalities play a crucial role in early detection and management, leading to improved outcomes for affected individuals. Regular screening enables the identification of suspicious lesions or abnormalities at earlier stages, facilitating timely intervention and potentially reducing mortality rates associated with breast cancer. Genetic mutations guide screening protocols, prophylactic interventions, treatment modalities, and patient prognosis. Prophylactic measures encompass a range of interventions, including chemoprevention, hormonal inhibition, oophorectomy, and mastectomy. Despite their efficacy in mitigating breast cancer incidence, these interventions carry potential side effects and psychological implications, necessitating comprehensive counselling tailored to individual cases.
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Neoplasias da Mama , Detecção Precoce de Câncer , Mastectomia Profilática , Humanos , Feminino , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/diagnóstico , Romênia/epidemiologia , Detecção Precoce de Câncer/métodos , Mastectomia Profilática/métodos , Mamografia/métodos , Fatores de RiscoRESUMO
Thoracic aortic dissection (TAD) is an important cause of sudden cardiac death and is characterized by high morbidity, mortality, and a poor prognosis. Patent ductus arteriosus (PDA) is a common congenital heart disease. The pathogenesis of both TAD and PDA has been reported to be related to genetic factors. The MYH11 gene, which encodes myosin heavy chain 11, has been reported in individuals with both TAD and PDA. Herein, we first detected a harmful MYH11 missense variant (c. T3728C, p. L1243P) in a TAD and PDA family. This missense variant co-segregated with the TAD/PDA phenotype in this family of four individuals, providing evidence of its harmfulness. Histopathological examinations revealed the presence of fragmented, broken, and lessened elastic fibers and the deposition of proteoglycans in the median of aortic dissection. Moreover, the immunofluorescence results showed that the labeled MYH11 protein in the tissue of the aortic dissection was weaker than that in the normal aorta. We present this familial case to stress the necessity of postmortem genetic testing in such cases among forensic practices. Identifying those culprit gene variants can direct effective genetic counseling and personalized health management in family members (especially first-degree relatives) with high-risk genotypes.
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Dissecção Aórtica , Dissecção da Aorta Torácica , Permeabilidade do Canal Arterial , Humanos , Permeabilidade do Canal Arterial/genética , Permeabilidade do Canal Arterial/patologia , Testes Genéticos , Dissecção Aórtica/genética , Aorta/patologia , Cadeias Pesadas de Miosina/genéticaRESUMO
OBJECTIVE: To analyze available literature data on the role of genetic factors in degenerative disc disease. METHODOLOGY: We reviewed the PubMed, MEDLINE, Cohrane Library, e-Library databases using the following keywords: degenerative spine lesions, intervertebral disc herniation, pathogenesis, genetic regulation. RESULTS: Searching depth was 2002-2022. We reviewed 84 references. Exclusion criteria: duplicate publications, reviews without detailed description of results, opinions. Finally, we included 43 the most significant studies. CONCLUSION: There are literature data on proinflammatory cytokines, growth factors and osteodestructive processes in pathogenesis of degenerative disc disease. However, there is only fragmentary information about the role of genetic regulation of these processes. Some factors, such as microRNA, TGF-b, VEGF, MMP are still poorly understood.