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Since the World Health Organization 2016 classification (2016 WHO), genetic status has been incorporated into the diagnosis of Grade 2/3 gliomas (lower-grade gliomas). Therefore, immunohistochemistry (IHC) of IDH1-R132H, ATRX, and p53 have been used in place of genetic status. We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21 IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglioma through morphological examination. Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.

In recent years, demand for medicinal plants increased due to the rise in attraction towards herbal products which are safer compared to modern drugs. Centella asiatica (L.) Urb is known as an important medicinal plant in herbal medicinal systems. It also used as an active ingredient for many products in the pharmaceutical and cosmetic industry. So far, review on this plant concerns mainly on medicinal, cosmetology and photochemical works reported. This review presents the genetic studies conducted in this herb along with a mention on conservation. Since documenting and studying genetic variation and its composition has an important connection for the understanding of evolution and improving the conservation of this species.

An adequate knowledge regarding the genetic issues of natural populations is imperative for developing conservation and stock improvement plans. The present research work was aimed to assess the genetic variability and structuring patterns in six natural populations of Cirrhinus mrigala from Punjab province, Pakistan. The PCR based amplification of targeted loci was carried out by employing a total of 12 microsatellite markers. Based on the study inferences, moderate level of genetic diversity was observed in all the populations. The average number of alleles (Na) varied from 3.750 to 4.416 and those of effective number of alleles ranged between 3.112 to 3.856 in all the examined populations. The mean values of observed and expected heterozygosity were measured as 0.563 to 0.685 and 0.669 to 0.739, respectively. The average values of inbreeding coefficient (FIS) ranged from 0.019 to 0.184. Significant deviation from HWE was detected in 9 out of 72 tests. Among all the population pairs, low to moderate level of genetic differentiation was found. After applying AMOVA, it was revealed that most of the variations (81.15%) lied within individuals. The UPGMA dendrogram resulted in two distinct clusters. The present study inferences would be helpful for setting up effective strategies to avoid the loss of genetic variability in C. mrigala populations.

Objective: The aim was to characterize the genetic diversity evolution of the registered Mexican Charolais cattle population by pedigree analysis. Methods: Data consisted of 331,390 pedigree records of animals born from 1934 to 2018. Average complete generation equivalent, generation interval, effective population size (Ne), and effective numbers of founders (fe), ancestors (fa), and founder genomes (Ng) were calculated for seven five-year periods. The inbreeding coefficient was calculated per year of birth, from 1984 to 2018, whereas the gene contribution of the most influential ancestors was calculated for the latter period. Results: Average complete generation equivalent consistently increased across periods, from 4.76, for the first period (1984 through 1988), to 7.86, for the last period (2014 through 2018). The inbreeding coefficient showed a relative steadiness across the last seventeen years, oscillating from 0.0110 to 0.0145. During the last period, the average generation interval for the father-offspring pathways was nearly 1 yr. longer than that of the mother-offspring pathways. The effective population size increased steadily since 1984 (105.0) and until 2013 (237.1), but showed a minor decline from 2013 to 2018 (233.2). The population displayed an increase in the fa since 1984 and until 2008; however, showed a small decrease during the last decade. The effective number of founder genomes increased from 1984 to 2003, but revealed loss of genetic variability during the last fifteen years (from 136.4 to 127.7). The fa:fe ratio suggests that the genetic diversity loss was partially caused by formation of genetic bottlenecks in the pedigree; in addition, the Ng:fa ratio indicates loss of founder alleles due to genetic drift. The most influential ancestor explained 1.8% of the total genetic variability in the progeny born from 2014 to 2018. Conclusion: Inbreeding, Ne, fa, and Ng are rather beyond critical levels; therefore, the current genetic status of the population is not at risk.

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and glucose in the small intestine. The genetic mechanism of lactase persistence in adult Caucasians is mediated by a single C→T nucleotide polymorphism at the LCTbo -13'910 locus on chromosome-2. Lactose malabsorption (LM) refers to any cause of failure to digest and/or absorb lactose in the small intestine. This includes primary genetic and also secondary LD due to infection or other conditions that affect the mucosal integrity of the small bowel. Lactose intolerance (LI) is defined as the onset of abdominal symptoms such as abdominal pain, bloating and diarrhoea after lactose ingestion by an individual with LM. The likelihood of LI depends on the lactose dose, lactase expression and the intestinal microbiome. Independent of lactose digestion, patients with visceral hypersensitivity associated with anxiety or the Irritable Bowel Syndrome (IBS) are at increased risk of the condition. Diagnostic investigations available to diagnose LM and LI include genetic, endoscopic and physiological tests. The association between self-reported LI, objective findings and clinical outcome of dietary intervention is variable. Treatment of LI can include low-lactose diet, lactase supplementation and, potentially, colonic adaptation by prebiotics. The clinical outcome of these treatments is modest, because lactose is just one of a number of poorly absorbed carbohydrates which can cause symptoms by similar mechanisms.

Maternal genetics is a key determinant of human milk oligosaccharide (HMO) composition in human milk. Beyond genetic status, other factors influencing the HMO profile are poorly defined. Thus, we aimed to review the existing evidence on the associations between nongenetic maternal and infant factors and HMO composition. A systematic search was performed on PubMed and Web of Science (without a time restriction) to identify any relevant studies published. In total, 1056 results were obtained, of which 29 articles were selected to be included in this review. The range of factors investigated include lactation stage, maternal pre-pregnancy BMI (ppBMI), maternal age, parity, maternal diet, mode of delivery, infant gestational age, and infant sex. The data suggest that, beyond maternal genetics, HMO composition seems to be influenced by all these factors, but the underlining mechanisms remain speculative. The published evidence is discussed in this review, along with potential implications for infant growth and development. For example, 2'-fucosyllactose, which was reportedly increased in mothers with higher ppBMIs, was also associated with increased infant weight and height. In addition, greater levels of sialylated HMOs after preterm birth may support brain development in these infants.

The tule elk (Cervus canadensis nannodes) is a California endemic subspecies that experienced an extreme bottleneck (potentially two individuals) in the mid-1800s. Through active management, including reintroductions, the subspecies has grown to approximately 6000 individuals spread across 22 recognized populations. The populations tend to be localized and separated by unoccupied intervening habitat, prompting targeted translocations to ensure gene flow. However, little is known about the genetic status or connectivity among adjacent populations in the absence of active translocations. We used 19 microsatellites and a sex marker to obtain baseline data on the genetic effective population sizes and functional genetic connectivity of four of these populations, three of which were established since the 1980s and one of which was established ~ 100 years ago. A Bayesian assignment approach suggested the presence of 5 discrete genetic clusters, which corresponded to the four primary populations and two subpopulations within the oldest of them. Effective population sizes ranged from 15 (95% CI 10–22) to 51 (95% CI 32–88). We detected little or no evidence of gene flow among most populations. Exceptions were a signature of unidirectional gene flow to one population founded by emigrants of the other 30 years earlier, and bidirectional gene flow between subpopulations within the oldest population. We propose that social cohesion more than landscape characteristics explained population structure, which developed over many generations corresponding to population expansion. Whether or which populations can grow and reach sufficient effective population sizes on their own or require translocations to maintain genetic diversity and population growth is unclear. In the future, we recommend pairing genetic with demographic monitoring of these and other reintroduced elk populations, including targeted monitoring following translocations to evaluate their effects and necessity.

This paper is devoted to the consideration of legal approaches to discrimination based on genetic status, formulated by the judicial practice of a number of foreign countries: Australia, the United States of America and Canada. The author notes that the regulatory framework for combating discriminatory practices based on genetic status has developed at the level of international law with the adoption of key documents in the relevant area. The author makes a conclusion about the ways to apply genetic information, which often acts as a “tool” for the implementation of discriminatory practices. As genetic testing becomes more widespread, the challenge will inevitably arise to determine what role genetic information should play in human and social life.

BRCA1 and BRCA2 pathogenic variant carriers have a high lifetime risk of developing breast and ovarian malignancies. Given the risks and significant ramifications of undergoing risk-reducing surgeries, many pathogenic variant carriers unaffected by cancer (previvors) struggle with family planning and reproductive decision making. The objective of this study was to determine the attitudes and practices of BRCA1 and BRCA2 pathogenic variant carriers with respect to family planning decision making. A cross-sectional survey was conducted of BRCA1 and BRCA2 previvors at four Northeastern medical centers. The survey was administered electronically via email using REDCap. The survey included demographic information as well as questions about genetic testing, prophylactic surgeries, family planning, and partnering. Data were analyzed with Fisher's exact tests and t tests. The survey was completed by 139 of 422 BRCA1 and BRCA2 pathogenic variant carriers (response rate 33%). Thirteen were excluded from analysis due to self-reported cancer history. Of the remaining 126, 21 (16.7%) were male and 105 (83.3%) were female. Female participants

The aim of this case report was to show the consequences of pregnancy in a cystic fibrosis (CF) patient with a rare mutation. We present a case of a patient with CF, pregnant for the second time, who gave birth to a healthy child. Her mutation status revealed the presence of relatively rare mutation c.3718-2477C>T that is associated with a milder phenotype of the disease. During pregnancy, her vital signs were within normal limits. She had no exacerbations after the third gestational month. Cystic fibrosis is the most common genetic disorder among Caucasians. Over the last few decades, the survival rate and the lifespan of patients with CF have increased progressively. This is why more affected women are choosing to become pregnant. Predictive factors for the pregnancy outcome are basal pulmonary function [measured by forced expiratory volume/1 second (FEV1)], nutritional status [measured by body mass index (BMI)], diabetes and bacterial colonization. The report of our case emphasizes the need for establishing the exact mutations in CF patients who plan to become pregnant in order to predict the possible outcomes of this specific period of life. Moreover, genetic counseling is strongly recommended for the right understanding of the pregnancy risks in such cases.

This study is part of a large interdisciplinary project to create objective criteria for building a classification system for a polymorphic schizophrenic disease characterized by disorders of thinking and perception. Within the framework of the project, for the first time in patients with schizophrenia with hallucinatory-delusional syndrome, neuropsychological testing, complete structural (morphometry and tractography) and functional MRI studies involving a detailed clinical study, determination of the patient’s immunological and genetic status are simultaneously performed. On the basis of a comprehensive analysis of MRI data, it is planned to determine the key architecture of the neural networks of the brain producing the disease, to assess the success of disease therapy and to determine the targets of subsequent therapy based on the application of the method of transcranial magnetic stimulation. This paper presents the primary results of work on the study of the difference between the structural connectomes of schizophrenic patients and the norm. The work is of a search and preliminary nature. As a result of the work, the possibility of classifying the disease was shown and the key structural links for it were identified.

Celem przeprowadzonych badań było przygotowanie populacji mapującej uzyskanej w wyniku skrzyżowaniaodmian ‘Elsanta’ i ‘Senga Sengana’, przydatnej do badań genotypowo-fenotypowych, poprzedzonych porządzeniem ‘szkieletu’ mapy genetycznej. Pierwszym etapem badań była ocena molekularna roślin form rodzicielskich pod kątem stopnia polimorfizmu genetycznego. Na postawie analizy wytypowanych 450 markerów SSR w genomie odmiany ‘Elsanta’ zidentyfikowano łącznie 418 alleli polimorficznych, natomiast w genomie odminay ‘Senga Sengana’ – 337 alleli. Przeprowadzone badania potwierdzają wysoki stopień heterozygotyczności genomów obu wytypowanych do badań odmian.Kolejnym etapem prac była analiza molekularna siewek uzyskanych w wyniku krzyżowania obu heterozygotycznych form rodzicielskich oraz ocena satusu genetycznego genotypów potomnych. Badania te potwierdziły, że w obrębie roślin populacji mapującej ‘Elsanta’ i ‘Senga Sengana’ występują genotypy pochodzące tylko z kontrolowanego zapylenia. Ponadto, analiza segregacji, w populacji mapującej, alleli heterozygotycznych, zidentyfkowanych w genomach form rodzicielskich, umożliwiła sporządzenie szkieltu zintegrowanej mapy obu badanych genomów truskawki. Wstępna mapa genetyczna, do sporządzenia której zastosowano wybranych 44 polimorficznych markerów SSR, zawiera łącznie 27 grup sprzężeń, na których zidentyfikowano loci 53 alleli polimorficznych, pokrywających 1 033 cM genomu truskawki. W wyniku przeprowadzonych testów potwierdzono, że uzyskana populacja stanowi wartościowy materiał do badań związanych z opracowaniem mapy genetycznej truskawki. Ponadto, sporządzony ‘szkielet’ mapy ‘Elsanta’ × ‘Senga Sengana’ poszerza bazę do dalszej lokalizacji genów i identyfikacji regionów QTL sprzężonych z ważnymi cechami użytkowymi truskawki.

BACKGROUND: Determination of isocitrate dehydrogenase (IDH) status and, if IDH-mutant, assessing 1p19q codeletion are an important component of diagnosis of World Health Organization grades II/III or lower-grade gliomas. This has led to research into noninvasively correlating imaging features (“radiomics”) with genetic status. PURPOSE: Our aim was to perform a diagnostic test accuracy systematic review for classifying IDH and 1p19q status using MR imaging radiomics, to provide future directions for integration into clinical radiology. DATA SOURCES: Ovid (MEDLINE), Scopus, and the Web of Science were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Diagnostic Test Accuracy guidelines. STUDY SELECTION: Fourteen journal articles were selected that included 1655 lower-grade gliomas classified by their IDH and/or 1p19q status from MR imaging radiomic features. DATA ANALYSIS: For each article, the classification of IDH and/or 1p19q status using MR imaging radiomics was evaluated using the area under curve or descriptive statistics. Quality assessment was performed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the radiomics quality score. DATA SYNTHESIS: The best classifier of IDH status was with conventional radiomics in combination with convolutional neural network–derived features (area under the curve = 0.95, 94.4% sensitivity, 86.7% specificity). Optimal classification of 1p19q status occurred with texture-based radiomics (area under the curve = 0.96, 90% sensitivity, 89% specificity). LIMITATIONS: A meta-analysis showed high heterogeneity due to the uniqueness of radiomic pipelines. CONCLUSIONS: Radiogenomics is a potential alternative to standard invasive biopsy techniques for determination of IDH and 1p19q status in lower-grade gliomas but requires translational research for clinical uptake.

Background Availability of genetic testing in neurodegenerative disorders has developed rapidly. This growing ability is providing specific genetic information to individuals and, in turn, their families, raising ethical concerns. However, family members' perspective is a seldom-studied phenomenon. Aim The aim of this systematic review was to describe the ethical aspect of genetic testing in neurodegenerative diseases from the perspective of at-risk family members. Method A systematic review of data was performed in accordance with the PRISMA statement. The data search was conducted using the CINAHL, PubMed and Scopus databases to identify original peer-reviewed studies published between January 2009 and April 2019. A total of 24 articles were selected. The data were analysed using inductive content analysis. Findings On the basis of the analysis, four central ethical implications were identified: (i) decision-making in genetic testing as a dilemma: balance between autonomy and responsibility, (ii) the individual's right to make a voluntary and informed decision for genetic testing, (iii) conflicting emotions after knowing one's genetic status and (iv) privacy and confidentiality of genetic information: the fear of genetic discrimination and stigma. Conclusions The findings of this review increase understanding about the central ethical implications of genetic testing in neurodegenerative diseases from the perspective of family members, and identify and underline outstanding needs for further research.

Mielodysplastic syndrome and hematopoietic stem cell transplantation based on genetic status.

The factors that form a teenager's health include biological factors (genetic status), the influence of socio-economic and environmental conditions. The state of reproductive health of adolescents can be attributed to the medical and social problem. On the basis of the study of scientific domestic and English-language publications over the past 10 years factors have been identified that form the health of adolescent children in the Russian Federation and the United States of America; the comparative characteristic of the reasons influencing the general level of health and its reproductive component has been given. It is proved that adolescent children who use drugs, tobacco, alcohol, are at risk for the development of deviations in the reproductive system. The knowledge of modern adolescent children on reproductive health is extremely poor, not all adolescents are focused on self-preserving behavior and there is no high-quality system of sex education and monitoring of reproductive health. The low awareness of children of this age group in reproductive health issues, the lack of a sex education system, and the weakening of the family's function in sex education issues lead to the early sexual activity, unwanted pregnancy, childbirth, and infection with sexually transmitted infections. The data presented indicate the need to create a single effective system for the prevention of reproductive diseases, the sex education system of the younger generation, affecting the formation of a holistic personality of a child, his health-saving behavior.

We review recent precision oncology literature pertaining to the implications of germline and somatic genetic information in cancer treatment. The goal of this work is to provide a practical resource for oncology practitioners and genetic providers and discuss practice considerations for those on the frontline of precision oncology. Understanding germline and somatic tumor alterations, patients can be matched to targeted therapy options attacking the specific genetic makeup of that tumor. This information informs treatment decisions about which therapies the cancer is likely to respond to and which treatment options should be avoided. Timely access to germline and somatic genetic testing is critical to ensure that patients have this information for treatment planning, both at diagnosis and through later lines of therapy. The hope of precision oncology is here although significant challenges remain for implementation for routine cancer care.

Cognitive impairment in Parkinson’s disease (PD) is pervasive with potentially devastating effects. Identification of those at risk for cognitive decline is vital to identify and implement appropriate interventions. Robust multivariate approaches, including fixed-effect, mixed-effect, and multitask learning models, were used to study associations between biological, clinical, and cognitive factors and for predicting cognitive status longitudinally in a well-characterized prevalent PD cohort (n = 827). Age, disease duration, sex, and GBA status were the primary biological factors associated with cognitive status and progression to dementia. Specific cognitive tests were better predictors of subsequent cognitive status for cognitively unimpaired and dementia groups. However, these models could not accurately predict future mild cognitive impairment (PD-MCI). Data collected from a large PD cohort thus revealed the primary biological and cognitive factors associated with dementia, and provide clinicians with data to aid in the identification of risk for dementia. Sex differences and their potential relationship to genetic status are also discussed.

Objective To elucidate the genetic background and genotype‐phenotype correlations for epilepsy with myoclonic‐atonic seizures, also known as myoclonic‐astatic epilepsy (MAE) or Doose syndrome. Methods We collected clinical information and blood samples from 29 patients with MAE. We performed whole‐exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. Results We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic‐atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention‐deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. Significance MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic‐atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

N6-methyladenosine (m6A) has an important epitranscriptomic modification that controls cancer self-renewal and cell fate. The addition of m6A to mRNA is a reversible modification. The deposition of m6A is encoded by a methyltransferase complex involving three homologous factors, jargonized as "writers," "erasers," and "readers." However, their roles in pancreatic adenocarcinoma (PAAD) are underexploited. With the use of The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we provided an mRNA signature that may improve the prognostic prediction of PAAD patients based on the genetic status of m6A regulators. PAAD patients with genetic alteration of m6A regulators had worse disease-free and overall survival. After comparing PAAD groups with/without genetic alteration of m6A regulators, we identified 196 differentially expressed genes (DEGs). Then, we generated a 16-mRNA signature score system through least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Multivariate cox regression analysis demonstrated that a high-risk score significantly correlates with poor prognosis. Moreover, time-dependent receiver operating characteristic (ROC) curves revealed it was effective in predicting the overall survival in both training and validation sets. PAH, ZPLD1, PPFIA3, and TNNT1 from our signature also exhibited an independent prognostic value. Collectively, these findings can improve the understanding of m6A modifications in PAAD and potentially guide therapies in PAAD patients.

PURPOSE OF REVIEW: This review explores the concepts of monogenic and the so-called polygenic familial hypercholesterolemia and how the identification of familial hypercholesterolemia as a monogenic condition and its separation from polygenic primary hypercholesterolemia may have implications for clinical practice. RECENT FINDINGS: Through genetic testing, a mutation in any of the three known autosomal dominant familial hypercholesterolemia-causing genes is found in 60-80% of cases with a clinical diagnosis of definite familial hypercholesterolemia. As individuals with a polygenic basis for their hypercholesterolemia do not follow the same inheritance pattern observed in monogenic familial hypercholesterolemia, the use of family-based cascade screening in individuals with a polygenic origin is not recommend, as only 30% of relatives have an elevated LDL-C compared to the 50% in monogenic families. The presence of a causative monogenic mutation associates the highest cardiovascular risk vs. not having a mutation or having a polygenic background, providing prognostic information independent of LDL-C. It may also help assess intensity of interventions. Treatment adherence also seems to be higher after monogenic confirmation of hypercholesterolemia. SUMMARY: Knowledge about the genetic status of an individual with clinical familial hypercholesterolemia (monogenic vs. polygenic) can provide a more informed understanding to evaluating risk, managing disease and opportunities for screening strategies.

Introduction The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo‐controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60‐year‐old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non‐carriers who receive placebo. Methods Of the 252 enrolled, we present data on a total of 242 mutation carriers and non‐carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. Results We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non‐carriers, 30 to 53 years of age. Carriers were significantly younger than non‐carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. Discussion Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non‐carriers. Their demographic characteristics are representative of the local population.

Purpose of Review This review uses clinical cases to highlight some of the ethical dilemmas currently faced by oncologists, geneticists and others who request genetic testing for inherited cancer disorders. Recent Findings Recent ethical guidance supports clinicians in testing patients when other family members decline similar testing, even when such testing will reveal those family members’ genetic status. And increasingly there is acknowledgement that when a patient declines to share genetic results with family members, clinicians may have an ethical duty to breach patient confidentiality in order to inform at-risk relatives to whom they may owe a duty of care, so that they can choose to access genetic testing and potentially life-saving screening and treatment. Summary Genetic testing for inherited cancer disorders raises multiple ethical issues, which cannot always be easily resolved by discussion with patients, or with their family members. Clinical ethics committees can provide valuable assistance in resolving the dilemmas presented in these cases.

Полиморфизм C1173T гена VKORC1 является одним из ключевых факторов, определяющих как этнические, так и индивидуальные различия в чувствительности к антикоагулянту варфарину и его поддерживающей дозе у пациентов при лечении тромбозозависимых заболеваний. В связи с этим, на популяционном уровне проведено исследование полиморфизма VKORC1 C1173T среди коренных представителей лесных ненцев Ямало-Ненецкого автономного округа и нганасан полуострова Таймыр Красноярского края. Генотипирование однонуклеотидных замен в гене VKORC1 проводилось в режиме реального времени с использованием конкурирующих TaqMan-зондов. Выявлено, что вариант VKORC1 1173T встречается с высокой частотой в изученных популяциях: 67% у лесных ненцев и 94% у нганасан. Этот показатель существенно и статистически значимо выше, чем у европейцев, и имеет схожий характер распространения с таковым у азиатов Китая и Японии. Результаты нашего исследования расширяют знания о полиморфизме гена VKORC1 в человеческих популяциях, а также способствуют развитию персонализированной медицины по отношению к коренным жителям Сибири, так как генетический статус человека, имеющего вариант 1173T, может учитываться в целях достижения максимально безопасной и эффективной терапии варфарином при тромбозозависимых заболеваниях. Polymorphism C1173T of the VKORC1 gene is one of the key factors determining both ethnic and individual differences in the sensitivity to the anticoagulant warfarin and its maintenance dose in patients in the treatment of thrombosis-dependent diseases. In this regard, at the population level the VKORC1 C1173T polymorphism was studied in indigenous populations of the Forest Nenets (the Yamal-Nenets Autonomous Okrug) and Nganasans (the Taimyr Peninsula of the Krasnoyarsk region). Genotyping of C1173T single nucleotide substitution in the VKORC1 gene was carried out in real time using competing TaqMan probes. It was revealed that the variant VKORC1 1173T occurs with a high frequency in the studied populations: 67% in Forest Nenets and 94% in Nganasans. This indicator is significantly higher than that of Europeans, and has a similar distribution pattern with that of Asians. The results of our study expand knowledge about VKORC1 gene polymorphism in human populations, and also promote the development of personalized medicine in relation to indigenous people of Siberia, since the genetic status of a person with variant 1173T can be taken into account at an individual level in order to achieve the most safe and effective warfarin therapy of thrombosis-dependent diseases.

Roanoke bass (Ambloplites cavifrons) persist in five river basins in the eastern US, where they are threatened by invasive species, habitat loss and degradation, and hydrologic fragmentation. We conducted the first conservation genetic study of A. cavifrons, analyzing variation at 19 nuclear microsatellite DNA loci and the cytochrome b mitochondrial DNA gene to estimate population structure and demography, genetic relationships among populations, and the role of landscape features in regulating genetic diversity and differentiation. Most streams harbored genetically distinguishable populations, with high connectivity among reaches within streams but no contemporary dispersal among streams. In contrast, mitochondrial divergence within and among basins was weak, suggesting historically higher range-wide connectivity. Most populations exhibited small effective population sizes and evidence of past population bottlenecks. Genetic diversity correlated positively with patch size but negatively with watershed urban and agricultural development, suggesting that habitat loss, degradation, and fragmentation have acted in concert to reduce population viability. Mitigating these impacts may require a combination of tactics, including restoring habitat, limiting the spread of invasive competitors, and reestablishing historical connectivity.

Introduction. A Hormon-like agent such as phenol is able both to integrate into the work of hypothalamus-pituitary-ovary system and trigger a cascade of responses that leads to the development of the immune, hormonal and endocrine systems disorder. Material and methods. The study included 181 woman who permanently live in the area with contamination with phenol in air above standard level. All women are comparable in age, material status and ethnicity. Immunological and hormonal indices were determined by enzyme immunoassay, genetic markers were detected by polymerase chain reaction. Statistical data processing was carried out with the soffware Statistica 10.0, using parametric and non-parametric methods. Results. Between the study groups there were obtained significant differences in following markers: thyroid-stimulating hormone, serotonin, interleukin 6, interleukin 10, estradiol. The dependence of appearance of unfavorable reproductive effects on the presence of polymorphic allele’s was determined: A allele of a gene SULT1A1, G allele of a gene PER2, C allele of a gene SIRT1. Correlation models are defined: thyroid-stimulating hormone and phenol, serotonin and phenol, thyroid-stimulating hormone and cresol, serotonin and cresol, estradiol and cresol. Conclusion. All found markers (increased concentration of phenol in biological media, gene polymorphism, altered protein and receptor expression) create special conditions for the course of the miscarriage pathology.

Purpose of review: The present review summarizes different polygenic risk scores associated with hypercholesterolemia applied to cohorts with a genetic diagnosis of familial hypercholesterolemia (FH). Recent findings: Several single-nucleotide polymorphisms associated with increased levels of LDL-C or Lp(a) have been genotyped in population cohorts with FH phenotype, to identify the cause of hypercholesterolemia in mutation negative individuals. In different studies, a large proportion of individuals without a monogenic causative variant (in low density lipoprotein receptor gene (LDLR), apolipoprotein B gene (APOB) or proprotein convertase subtilisin/kexin type 9 gene (PCSK9 genes) was considered to have a hypercholesterolemia with a polygenic basis. The heterogeneity in the phenotype of monogenic FH may also be explained by polygenic contributions to LDL-C. The elevated LDL-C genetic risk score (GRS) has been associated with increased risk of atherosclerotic cardiovascular disease in individuals with monogenic FH. Moreover, a poorer response to lipid lowering therapy has been associated with monogenic FH when compared to a polygenic basis. The reason why Lp(a) concentrations are raised in individuals with clinical FH is unclear, but it could be caused by a genetic variation in Lipoprotein(A) gene as a polygenic contribution. Summary: Polygenic risk scores have revealed to be important tools to define the cause of hypercholesterolemia in FH mutation-negative individuals and should be included in FH diagnosis strategies, although there is still space for more specific LDL-C GRS to be developed. The use of GRS may be used to refine cardiovascular risk prediction in FH patients and could lead to a personalized approach to therapy. The identification of the genetic status of an individual with FH phenotype (monogenic or polygenic) may have implications on their risk stratification, cascade screening of relatives, disease management and therapeutic measures. A.M.M. was supported by a PhD fellowship (2016-2019) from Science and Technology Foundation (Ref. SFRH/BD/113017/2015). info:eu-repo/semantics/publishedVersion

Domestic animals have immense economic, cultural, and practical value and have played pivotal roles in the development of human civilization. Many domesticates have, among their wild relatives, undomesticated forms representative of their ancestors. Resurgent interest in these ancestral forms has highlighted the unclear genetic status of many, and some are threatened with extinction by hybridization with domestic conspecifics. We considered the contemporary status of these ancestral forms relative to their scientific, practical, and ecological importance; the varied impacts of wild-domestic hybridization; and the challenges and potential resolutions involved in conservation efforts. Identifying and conserving ancestral forms, particularly with respect to disentangling patterns of gene flow from domesticates, is complex because of the lack of available genomic and phenotypic baselines. Comparative behavioral, ecological, and genetic studies of ancestral-type, feral, and domestic animals should be prioritized to establish the contemporary status of the former. Such baseline information will be fundamental in ensuring successful conservation efforts.Los Ancestros de Animales Domésticos como un Componente Descuidado y Amenazado de la Biodiversidad Resumen Los animales domésticos tienen un inmenso valor económico, cultural y práctico y han jugado un papel muy importante en el desarrollo de la civilización humana. Muchos animales domesticados tienen, entre sus parientes silvestres, formas no domesticadas representativas de sus ancestros. Un interés renovado en estas formas ancestarles ha destacado el estatus genético poco claro de muchas, y algunas están amenazadas de extinción por hibridación con conespecíficos domesticados. Consideramos el estatus contempóraneo de estas formas ancestrales en relación con su importancia científica, práctica y ecológica; los impactos diversos de la hibridación silvestre-domesticado; y los retos y soluciones potenciales involucrados en los esfuerzos de conservación. La identificación y conservación de formas ancestrales, particularmente en relación con desenredar patrones de flujo génicos, es compleja debido a la carencia de líneas de base genómicas y fenotípicas. Se deben priorizar estudios conductuales, ecológicos y genéticos comparativos de los animales ancestrales, ferales y domésticos para establecer el estatus contemporáno de los primeros. Tal información de base será fundamental para asegurar esfuerzos de conservación exitosos.【摘要】家畜具有巨大的经济、文化和实用价值, 在人类文明的发展中发挥了关键作用。许多家畜的野生近缘物种中都有代表其祖先型的未驯化动物。重新关注这些祖先型的动物, 会发现其中许多的遗传状态不明确, 还有些因为与同种的家畜发生杂交而面临灭绝的威胁。我们分析了这些祖先型动物目前在科学、实用和生态方面的重要性、野生动物与家畜杂交的各种影响, 以及保护工作中的挑战和潜在的解决方案。由于缺乏可用的基因组和表型基线数据, 识别和保护祖先型动物仍是十分复杂的问题, 特别是解析其受到来自家畜的基因流模式。我们建议应优先考虑对祖先型动物、野生动物和家畜的行为学、生态学和遗传学进行比较研究, 以确定前者当前的状态。这些基线信息是确保保护工作成功的基础。【翻译: 胡怡思; 审校: 聂永刚】.

A comprehensive study was undertaken to understand the genetic status and help to clarify the division of Medicago rigidula (largely European) and Medicago rigiduloides (largely Asian). Genetic diversity parameters collectively suggested a low genetic diversity (avg. Ho, 0.073; He, 0.374) accompanied by high population differentiation (avg. F, 0.832; Gst, 0.362). Structure analysis divided 71 individuals (14 Iranian populations) into two highly distinct genetic groups (K=2) with significant genetic homogeneity. It also indicated the strong effect of the selfing mating-system as the main reason for the genetic diversity status and population structure. The population grouping was strongly confirmed by various clustering methods. Populations from north and northwestern Iran made up a distinctive genetic group corresponding to M. rigidula while the second group corresponding to M. rigiduloides harboured the western and two of the northwestern populations. The outcomes of this study provide the first reliable molecular evidence supporting the M. rigidula-M. rigiduloides separation previously suggested by morphology.

The purpose of this study is to outline the geneticization of deviant behavior, in the light of critical criminology and sociology of genetics, as a modern cross-disciplinary approach in the field of social sciences. Adopting theoretically the conflict model of analysis, genetic is viewed as a social phenomenon and socio - historical system of ideas formed by the dominant perceptions and interests that will predominate in the current social reality and historical period (social formatted), interfering authoritatively in society, the individual and social relations. In the light of Foucault's work, the genetic system of knowledge - power (as a result of the scientific medical knowledge), in the form of discourse, reproduces the dominant values and principles, constructing by the genetic determinism and reductionism the “deviant genes” and therefore the “candidate criminal genes” (after the “born criminal” of Lombroso), reintroducing the ondological reality of crime in the genetic “defectiveness” of the individual. On account of this pathologicalization and criminalization of the human genome, the whole problem is shifted to the issue of penalization, through the insertion of these data in the courtrooms, highlighting the issue of deterministic trial, hence the “conviction of the gene” or “genome offender”. Additionally, the constitution of the genetic criminal policies, led to the “cell surveillance”, the wrapping of population through genetic data files, and inevitably in the devising policies “treatment” for the “gene disease of crime”. Observing the whole question originating from the search of the “criminality pill”, the re-establishment of methods such as chemical castration - hormone suppressing and extending to the vision of gene therapy, the reconstruction or repair of genetic code. The “cell anatomy” turns into "social anatomy" and the geneticization of the society, constructing the “social class of the gene”. The issue initiates from the transition of “anarchists” of Lombroso in the politicized genes of the lefts and the “political ideology of the genetic code” and extend to the political economy of genetic, under the bio-capitalism / bio-imperialism and neoliberal politics of bio-economy, leading to the commercialization of life. As opposed to the above ideas, it has been found significant the “resistance of the genetic material” through collective action and social movements - bioclaims, the core of which is the inherent freedom of genetic status or rather the existence itself “from below”.%%%%Η παρούσα μeλέτη, αποσκοπeί στη σκιαγράφηση της γeνeτικοποίησης της παρeκκλίνουσας συμπeριφοράς, υπό το πρίσμα της κριτικής eγκληματολογίας και της κοινωνιολογίας της γeνeτικής, ως μία σύγχρονη διeπιστημονική προσέγγιση στο χώρο των κοινωνικών eπιστημών. Υιοθeτώντας θeωρητικά το συγκρουσιακό μοντέλο ανάλυσης, η γeνeτική προσλαμβάνeται ως κοινωνικό φαινόμeνο και κοινωνικo-ιστορικό σύστημα ιδeών, το οποίο διαμορφώνeται μe βάση τις κυρίαρχeς αντιλήψeις και συμφέροντα που θα υπeρισχύσουν στην eκάστοτe κοινωνική…

Modern management of acute myeloid leukaemia (AML) relies on the integration of phenotypic and genetic data to assign classification, establish prognosis, enhance monitoring and guide treatment. The prism through which we can now disperse a patient's leukaemia, interpret and apply our understanding has fundamentally changed since the completion of the first whole-genome sequencing (WGS) of an AML patient in 2008 and where possible, many clinicians would now prefer to delay treatment decisions until the karyotype and genetic status of a new patient is known. The success of global sequencing initiatives such as The Cancer Genome Atlas (TCGA) have brought us significantly closer to cataloguing the full spectrum of coding mutations involved in human malignancy. Indeed, genetic capability has raced ahead of our capacity to apply much of this knowledge into clinical practice and we are in the peculiar position of having routine access to genetic information on an individual patient's leukaemia that cannot be reliably interpreted or utilised. This is a measure of how rapid the progress has been, and this rate of change is likely to continue into the foreseeable future as research intensifies on the non-coding genome and the epigenome, as we scrutinise disease at a single cell level, and as initiatives like Beat AML and the Harmony Alliance progress. In this review, we will examine how interrogation of the coding genome is revolutionising our understanding of AML and improving our ability to underscore differences between paediatric and adult onset, sporadic and inherited forms of disease. We will look at how this knowledge is informing improvements in outcome prediction and the development of novel treatments, bringing us a step closer to personalised therapy for myeloid malignancy.

The improvement of the medical genetic counseling, the routinisation of this area of medical practice leads to a change in the model of the physician-patient relationship, and also requires a revision of the basic ethical rules that underlie medical practice. The feature of the medical genetic counseling is that the information obtained as a result of DNA analysis is significant not only for the individual patient, but also for his relatives. Thus, the subject of communication is not one patient, but his whole family. The physician is faced with the problem of reconciling the interests of the patient and his relatives, who can be at risk. Modern man is more appreciative of the relationship based on an emotional relationship. However, knowledge of their genetic status, the importance of informing relatives about the mutation leads to an increase in the role of biological kinship. The feature of the medical genetic counseling does not allow to fully implement the basic bioethical principles: non-maleficence, beneficence, autonomy, justice. The improvement of the medical genetic counseling practices and their effectiveness are impossible without the transformation of rules and procedures aimed at the possibility of communication with the patient's relatives. One solution is to develop informed consent forms that limit the right of an individual patient to dispose of genetic information. An equally important mechanism to overcome the problems faced by genetic consulting is conducting PR campaigns and additional consultations aimed at improving the genetic competence of the people and loyalty to the genetic laboratories.

BACKGROUNDPreimplantation genetic testing (PGT) encompasses methods that allow embryos to be tested for severe inherited conditions or for chromosome abnormalities, relevant to embryo health and viability. In order to obtain embryonic genetic material for analysis, a biopsy is required, involving the removal of one or more cells. This invasive procedure greatly increases the costs of PGT and there have been concerns that embryo viability could be compromised in some cases. The recent discovery of DNA within the blastocoele fluid (BF) of blastocysts and in spent embryo culture media (SCM) has led to interest in the development of non-invasive methods of PGT (niPGT).OBJECTIVE AND RATIONALEThis review evaluates the current scientific evidence regarding non-invasive genetic assessment of preimplantation embryos. The success of different PGT methodologies in collecting and analysing extra-embryonic DNA is evaluated, and consideration is given to the potential biological and technical hindrances to obtaining a reliable clinical diagnosis.SEARCH METHODSOriginal research and review papers concerning niPGT were sourced by searching PubMed and Google Scholar databases until July 2019. Searches comprised the keywords: ‘non-invasive’; ‘cell-free DNA’; ‘blastocentesis’; ‘blastocoel fluid’; ‘spent culture media’; ‘embryo culture medium’; ‘preimplantation genetic testing’; ‘preimplantation genetic diagnosis’; ‘preimplantation genetic screening’; and ‘aneuploidy’.OUTCOMESEmbryonic DNA is frequently detectable in BF and SCM of embryos produced during IVF treatment. Initial studies have achieved some success when performing cytogenetic and molecular genetic analysis. However, in many cases, the efficiency has been restricted by technical complications associated with the low quantity and quality of the DNA. Reported levels of ploidy agreement between SCM/BF samples and biopsied embryonic cells vary widely. In some cases, a discrepancy with respect to cytogenetic data obtained after trophectoderm biopsy may be attributable to embryonic mosaicism or DNA contamination (usually of maternal origin). Some research indicates that aneuploid cells are preferentially eliminated from the embryo, suggesting that their DNA might be over-represented in SCM and BF samples; this hypothesis requires further investigation.WIDER IMPLICATIONSAvailable data suggest that BF and SCM samples frequently provide DNA templates suitable for genetic analyses, offering a potential means of PGT that is less expensive than traditional methods, requires less micromanipulation skill and poses a lower risk to embryos. Critically, DNA isolation and amplification protocols must be optimised to reproducibly obtain an accurate clinical diagnosis, whilst minimising the impact of confounding factors such as contamination. Further investigations are required to understand the mechanisms underlying the release of embryonic DNA and to determine the extent to which this material reflects the true genetic status of the corresponding embryo. Currently, the clinic al potential of niPGT remains unknown.

The linebreeding of southern African antelope species, involving selection for specific coat colour phenotypes, is a wide-spread practice in the South African game farming industry. Concerns have been voiced with regards to the genetic status of these line-bred colour variants, due to the high risk of inbreeding. The springbok (Antidorcas marsupialis) is one of the most well-known examples of such linebreeding. Numerous colour variants have been observed, with the most notable the black, copper and white colour phenotypes. To our knowledge, no research has been performed on the genetic basis of these springbok colour variants. In this study, we aimed to 1) assess the level of genetic variation within and among the common, black, copper and white colour variants of springbok, and 2) investigate the possible genetic mechanisms involved in the coat colour of these variants. Portions of the mtDNA control region (CR) and two immune-linked Toll-like receptor (TLR4 and TLR7) genes were sequenced for the genetic diversity estimates. A 50 K Bovine SNP chip was also screened to assess the level of genetic diversity of a subset of samples. The complete melanocortin 1 receptor (MC1R) gene was targeted for the second aim. Comparable levels of diversity were identified across specimens. Pairwise genetic diversity analysis of the SNP data identified the white springbok as a unique group within springbok, with Bayesian clustering analysis supporting this observation. A possible reason for this clustering pattern was linked to the historical occurrence of white springbok in nature. The level of genetic diversity observed for each colour variant was associated with 1) the large historical and extant population sizes of springbok providing a deep genetic pool and/or 2) the management practices of the managers/farmers that are aimed at preventing or minimizing inbreeding and loss of genetic diversity. The MC1R assessment identified a nonsynonymous SNP (c. G902A) unique to white springbok (homozygous AA). A 24 bp deletion was observed in black, copper and king springbok colour variants. This deletion was complete for ∼21 % of black springbok. The heterozygous variant was observed in ∼88 % of copper springbok and ∼5 % of black springbok. This would suggest that additional genetic factors are involved in coat colour determination (due to the incomplete association of the 24 bp deletion). Further research is therefore needed to identify the other possible genetic factors involved.

We examined the benefit of emotional support on daily health in premutation carrier mothers of adolescents and adults with fragile X syndrome (n = 114), and whether this benefit was moderated by the mother's genetic status (FMR1 CGG repeat length). In an 8-day daily diary, maternal daily health was assessed subjectively through self-reported number of physical health symptoms and physiologically via cortisol awakening response. Multilevel lagged-day models indicated that premutation carrier mothers with midrange CGG repeats derived less health benefit from a day with high positive emotional support than those with lower or higher numbers of repeats within the premutation range. The data support the influence of both genetic and environmental influences on the health of this population.

Eryngium viviparum (Apiaceae) is an endangered endemic plant of the Atlantic region of Europe, growing in seasonally flooded sites, and is characterized by a highly disjunct distribution. It occurs in just a few sites in the north-western part of the Iberian Peninsula and in a single locality in France. To improve the conservation status of E. viviparum in France, a conservation programme has been implemented to reintroduce the species. Before considering such an operation, genetic studies were conducted to determine the genetic status of the last French population and to identify the genetic source that should be considered for the best reintroduction strategy. Using microsatellite markers, we documented the genetic structure of the last French population and compared its genetic diversity with that of ten Iberian populations, which cover the three geographical regions where the species occurs. As expected, the French population of E. viviparum shows low genetic diversity due to a bottleneck and geographical isolation. The evolutionary potential appears low, with no private alleles in this population. Furthermore, this population is highly differentiated from the Iberian populations in terms of genetic variation and ecological niche. These results bring new questions regarding the conservation of E. viviparum in France, especially for management and reintroduction aimed at favouring genetic diversity and avoiding extinction.

Pantothenate kinase-associated neurodegeneration (PKAN) is linked to brain iron accumulation caused by PANK2 gene mutation. Despite the importance of genetic testing to confirm PKAN and identify at risk parents, genetic screening is financially burdensome for developing countries like Thailand. Because genetic screeners are expensive and not reimbursed by the universal health care coverage system, they are not typically performed. To investigate clinical symptoms, radiological findings and mutation analysis for patients based in Thailand with unknown genetic status but suspected PKAN based on clinical symptoms. Genetic testing was performed for cases suspected for PKAN and their biological parents by direct genomic sequencing of PANK2 at Maharat Nakhon Ratchasima Hospital during 2017–2018. Clinical evaluation and documentation were performed by pediatric neurologists. Five children had classical onset form of PKAN. Most presented with gait dystonia. Three patients diagnosed after 4 years showed the eye-of-the-tiger sign in their brain MRI, whereas two younger patients revealed only isolated hyperintensity bilateral globus pallidus. However, PANK2 mutations were identified in all cases: the most common mutation was c.982-1G>C. This mutation was detected in four unrelated individuals but not reported in other studies. Genetic testing is recommended to confirm diagnoses in cases with supporting clinical features of PKAN with or without the classical ‘eye-of-the-tiger-sign’. A novel PANK2 mutation (c.982-1G>C) was identified in South East Asian populations based in Thailand, suggesting that this genetic variant is a founder genotype in this population. Moreover, genetic diagnosis is helpful to provide appropriate genetic counseling to families.