Genetic Point Of View Research Articles

Genetic diversity and conservation evaluation of a critically endangered endemic maple, Acer yangbiense, analyzed using microsatellite markers

The newly discovered endemic maple Acer yangbiense of China has only five individuals left in the wild, and thus has been classified as a plant species with extremely small populations (PSESP). PSESP species call for emergency protection procedures, such as ex-situ conservation and reintroduction. Our objectives were to examine the genetic diversity of A. yangbiense and to evaluate former conservation strategies from a genetic point of view. Our results suggested that A. yangbiense was not genetically depauperate, but its genetic loss at a species level was obvious. A parentage analysis indicated a high selfing-rate in A. yangbiense and suggested the existence of a previously unknown wild individual. Former conservation strategies did not include all genetic variations of the wild population, and gene diversity of the ex-situ conserved seedlings is lower than that of the wild population. From our findings, we make suggestions to guide the subsequent protection of this species.

MtDNA Haplogroup A10 Lineages in Bronze Age Samples Suggest That Ancient Autochthonous Human Groups Contributed to the Specificity of the Indigenous West Siberian Population.

BackgroundThe craniometric specificity of the indigenous West Siberian human populations cannot be completely explained by the genetic interactions of the western and eastern Eurasian groups recorded in the archaeology of the area from the beginning of the 2nd millennium BC. Anthropologists have proposed another probable explanation: contribution to the genetic structure of West Siberian indigenous populations by ancient human groups, which separated from western and eastern Eurasian populations before the final formation of their phenotypic and genetic features and evolved independently in the region over a long period of time. This hypothesis remains untested. From the genetic point of view, it could be confirmed by the presence in the gene pool of indigenous populations of autochthonous components that evolved in the region over long time periods. The detection of such components, particularly in the mtDNA gene pool, is crucial for further clarification of early regional genetic history.Results and ConclusionWe present the results of analysis of mtDNA samples (n = 10) belonging to the A10 haplogroup, from Bronze Age populations of West Siberian forest-steppe (V—I millennium BC), that were identified in a screening study of a large diachronic sample (n = 96). A10 lineages, which are very rare in modern Eurasian populations, were found in all the Bronze Age groups under study. Data on the A10 lineages’ phylogeny and phylogeography in ancient West Siberian and modern Eurasian populations suggest that A10 haplogroup underwent a long-term evolution in West Siberia or arose there autochthonously; thus, the presence of A10 lineages indicates the possible contribution of early autochthonous human groups to the genetic specificity of modern populations, in addition to contributions of later interactions of western and eastern Eurasian populations.

Progress in understanding the diagnosis and molecular genetics of macrothrombocytopenias.

The inherited macrothrombocytopenias constitute a subgroup of congenital platelet disorders that is the best characterized from the genetic point of view. This clinically heterogeneous subgroup is characterized by a variable degree of bleeding but without predisposition to haematological malignancies, as seen in the two other subgroups. The classification of inherited thrombocytopenia is traditionally based on the description of different clinical and biological features, in particular the measurement of the mean platelet volume. In certain disorders, biochemical platelet components are abnormal, and their analyses are useful in diagnosis. However, these approaches present several limitations, and many cases remain undiagnosed, especially for patients without a clear family history. An analysis of genetic abnormalities was subsequently used for classification, demonstrating that some different clinical entities were, in fact, identical. The genomic approach that was used initially to accurately link some phenotypic diagnoses with the causal genetic alteration was positional cloning and DNA sequencing. More recently, next generation sequencing in the form of whole-genome or -exome sequencing and RNA sequencing has been developed. This review will focus on the progress in understanding the different macrothrombocytopenias that have been identified.

Temporal sequence of hard and soft tissue healing around titanium dental implants.

The objective of the present review was to summarize the evidence available on the temporal sequence of hard and soft tissue healing around titanium dental implants in animal models and in humans. A search was undertaken to find animal and human studies reporting on the temporal dynamics of hard and soft tissue integration of titanium dental implants. Moreover, the influence of implant surface roughness and chemistry on the molecular mechanisms associated with osseointegration was also investigated. The findings indicated that the integration of titanium dental implants into hard and soft tissue represents the result of a complex cascade of biological events initiated by the surgical intervention. Implant placement into alveolar bone induces a cascade of healing events starting with clot formation and continuing with the maturation of bone in contact with the implant surface. From a genetic point of view, osseointegration is associated with a decrease in inflammation and an increase in osteogenesis-, angiogenesis- and neurogenesis-associated gene expression during the early stages of wound healing. The attachment and maturation of the soft tissue complex (i.e. epithelium and connective tissue) to implants becomes established 6-8 weeks following surgery. Based on the findings of the present review it can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.

REPRODUCTIVE SYSTEM AND POLLEN FLOW IN PROGENIES OF Qualea grandiflora Mart., A TYPICAL SPECIES OF THE BRAZILIAN CERRADO

This study analyzed the reproductive system and the pollen dispersion pattern of Qualea grandiflora progenies. This is a typical species from the Brazilian Cerrado about which there are not too many studies from the genetics point of view. The study was conducted in an area of 2.2 hectares located in the Conservation Unit managed by the Forest Institute of the state of São Paulo, Brazil (Assis State Forest). Total genomic DNA of 300 seeds from 25 plants (12 seeds from each plant) was extracted and amplified using specific primers to obtain microsatellite markers. Results showed that selfing is frequent among adults and progenies, and the species reproduces by outcrossing between related and unrelated individuals (0.913). The single-locus outcrossing rate was 0.632, which indicates that mating between unrelated individuals is more frequent than between related plants. The selfing rate was low (0.087), that is, the species is allogamous and self-fertilization is reduced. About 35% of the plants in the progenies were full-sibs, and about 57%, half-sibs. Besides, about 8% of the progenies were selfing siblings. The genetic differentiation coefficient within progenies was 0.139, whereas the fixation rate was about 27%. The estimate of the effective size revealed that the genetic representativeness of descent was lower than expected in random mating progenies: The analyzed samples corresponded to only 13.2 individuals of an ideal panmictic population. In environmental recovery programs, seeds, preferably from different fruits, should be collected from 95 trees to preserve the genetic diversity of the species.

The evolution of sex differences in disease.

It is now becoming widely recognized that there are important sex differences in disease. These include rates of disease incidence, symptoms and age of onset. These differences between the sexes can be seen as a subset of the more general phenomenon of sexual dimorphism of quantitative phenotypes. From a genetic point of view, this is paradoxical, since the vast majority of genetic material is shared between the sexes. How can males and females differ in so many ways and yet have a common genetic code? Traditionally, the modifying action of hormones has been offered as a solution to this paradox, but experiments disentangling the effects of hormones and sex-chromosomes have shown that this cannot be the sole explanation. In this review, I outline current ideas about the evolutionary origins of sex differences in phenotypes, with a particular focus on how sex differences in disease can arise. I also discuss how sex differences in themselves can generate new risk factors for disease, in effect becoming a new environmental factor, as well as briefly reviewing more general evidence for sexually antagonistic selection and genetic variation within humans. Taking an evolutionary view on sex differences in disease provides an opportunity for greater understanding of mechanisms of disease and as such provides a clear motivation for clinicians to explore how therapies may be tailored to the individual in a sex-dependent way.

Genetic and morphological diversity in Cousinia tabrisiana (Asteraceae) populations

AbstractCousinia Cass. is one of the largest genuses in the Asteraceae. It contains 600 to 700 species in Southwest and Central Asia, in Iran with 270 species is the largest genus after Astragalus, Cousinia probably is unique in the degree of diversification of all its parts and definitely unique in the restricted distribution area of a high number of species. Some of Cousinia species have medicinal value. Perhaps the most important biological challenge today is the conservation of biodiversity. As human population increases, so does the need for natural resources and space for the growing population. In this investigation eighty-seven plant specimens of 8 geographical populations of Cousinia tabrisiana Bunge. were studied from morphological and genetic (ISSR) points of view. Both intra and inter-population morphological and genetic variability was observed in the studied populations. ANOVA and CVA tests revealed significant morphological difference among these populations. Similarly, AMOVA and Hickory tests revealed significant molecular difference among geographical populations. Mantel test produced significant positive correlation between genetic distance and geographical distance of the studied populations. Networking, STRUCTURE analysis and population assignment test revealed some degree of gene flow among these populations. LMFF test identified some of the ISSR loci to be correlated with environmental factors studied and consensus tree of morphological and genetic data identified divergent populations.

Cousin Marriages from Viewpoint of Genetics.

Cousin Marriages from Viewpoint of Genetics.

Alcohol addiction: a molecular biology perspective.

Alcohol misuse represents worldwide an important risk factor for death and disability. Excessive alcohol consumption is widely diffused in different ethnicities and alcohol use is part of the lifestyle of both young and old people. The genetic basis of alcohol dependence concerning ethanol metabolism and the pathways of reward circuits are well known. The role of genetic variants in the neurobiology of addiction as well as in response to medication in alcoholism therapy still represents an intriguing argument that needs to be deeply analyzed and explained. The molecular approach to the study of these aspects could be difficult because of the large number of genes and variations involved. Our work is intended to offer an overview of genes and variants involved in alcohol addiction and pharmacogenetics. Our aim is to delineate a molecular approach strategy to look at alcohol dependence from a genetic and applicative point of view. The indications provided in this work should be of help for those who wish to undertake a molecular study of this multifactorial disease.

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis.

Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype-phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype-phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype-phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway.

Circulating microRNAs in Neurodegenerative Diseases.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by a combination of events that impair normal neuronal function. Although they are considered different disorders, there are overlapping features among them from the clinical, pathological, and genetic points of view. Synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities such as axonal transport defects normally precede the neuronal loss that is a relatively late event. The diagnosis of many neurodegenerative diseases is mainly based on patient's cognitive function analysis, and the development of diagnostic methods is complicated by the brain's capacity to compensate for neuronal loss over a long period of time. This results in the late clinical manifestation of symptoms, a time when successful treatment is no longer feasible. Thus, a noninvasive diagnostic method based on early events detection is particularly important. In the last years, some biomarkers expressed in human body fluids have been proposed. microRNAs (miRNAs), with their high stability, tissue- or cell type-specific expression, lower cost, and shorter time in the assay development, could constitute a good tool to obtain an early disease diagnosis for a wide number of human pathologies, including neurodegenerative diseases. The possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative disorders is a highly promising approach for developing minimally invasive screening tests and to identify new therapeutic targets.

Isolation and characterization of polymorphic EST-SSR and genomic SSR markers in spotted mandarin fish (Siniperca scherzeri Steindachne)

Spotted mandarin fish (Siniperca scherzeri Steindachne) feed solely on live fry of other fish species once the fry start feeding in the wild. In the present study, 26 polymorphic transcriptome-derived simple sequence repeat (SSR) markers and 14 genomic SSR markers were developed and characterized in S. scherzeri Steindachne by combining a biotin-enrichment protocol and transcriptome of F1 interspecies hybrids between S. chuatsi (♀) and S. scherzeri (♂). These 40 polymorphic SSRs amplified 168 alleles (mean 4.2). The number of alleles, observed heterozygosity, expected heterozygosity, and polymorphic information content per locus were in the range of 2 to 7 (mean 4.3), 0.1111 to 1.000 (mean 0.6718), 0.3118 to 0.8276 (mean 0.6901), and 0.2735 to 0.7902 (mean 0.6298), respectively. Ten of these microsatellite loci deviated significantly from Hardy-Weinberg equilibrium (P < 0.00125) after Bonferroni correction for multiple tests and no significant linkage disequilibrium (P < 0.00006) was observed. The microsatellite markers characterized from S. scherzeri could be a valuable tool in genetic evaluation for conservation and for assessment of the mechanism associated with unique food preference of S. scherzeri from a genetic point of view.

Next generation sequencing applications for breast cancer research.

For some time, cancer has not been thought of as a disease, but as a multifaceted, heterogeneous complex of genotypic and phenotypic manifestations leading to tumorigenesis. Due to recent technological progress, the outcome of cancer patients can be greatly improved by introducing in clinical practice the advantages brought about by the development of next generation sequencing techniques. Biomedical suppliers have come up with various applications which medical researchers can use to characterize a patient’s disease from molecular and genetic point of view in order to provide caregivers with rapid and relevant information to guide them in choosing the most appropriate course of treatment, with maximum efficiency and minimal side effects. Breast cancer, whose incidence has risen dramatically, is a good candidate for these novel diagnosis and therapeutic approaches, particularly when referring to specific sequencing panels which are designed to detect germline or somatic mutations in genes that are involved in breast cancer tumorigenesis and progression. Benchtop next generation sequencing machines are becoming a more common presence in the clinical setting, empowering physicians to better treat their patients, by offering early diagnosis alternatives, targeted remedies, and bringing medicine a step closer to achieving its ultimate goal, personalized therapy.

Hereditary Angioedema Due to C1-Inhibitor Deficiency – From a Genetic Point of View

Hereditary Angioedema Due to C1-Inhibitor Deficiency – From a Genetic Point of View

Molecular-genetic aspects of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is the world's most abundant and the most common heritable disorder of lipid metabolism. The prevalence of the disease in general population is 1:500. Therefore the approximate number of FH patients all over the world is 14 million. From the genetic point of view the disease originates as a result of mutations in genes affecting the processing of LDL particles from circulation, resulting in an increase in LDL cholesterol and hence total cholesterol. These are mutations in genes encoding LDL receptor, apolipoprotein B, proprotein convertase subtilisin/kexin 9 and LDL receptor adaptor protein 1. Cholesterol depositing in tissues and blood vessels of individuals creates tendon xanthoma, xanthelesma and arcus lipoides cornae. Due to the increased deposition of cholesterol in blood vessels, atherosclerosis process is accelerated, what leads to a significantly higher risk of premature cardiovascular diseases. Therefore, early clinical diagnosis confirmed by the DNA analysis, and effective treatment are crucial to reduce the mortality and high risk of premature atherosclerotic complications.

Craniometric analysis for estimation of stature in Nepalese population—A study on an autopsy sample

Establishing the identity of the deceased becomes essential when highly decomposed bodies, mutilated body parts or skeletal remains are recovered from mass fatality sites. In these situations, estimation of stature along with other parameters such as age, sex and race/ethnicity becomes important to establish the biological profile of the deceased. Following the Maoist insurgency in Nepal, there have been numerous discoveries of unidentified human remains in mass graves or otherwise. No systemic studies and anthropological data on the Nepalese population however, is available posing problems in anthropologic evaluation of the remains. The sample of the present study consisted of 200 autopsied cases (148 males and 52 female adult cadavers). During the autopsy, the scalp was reflected after giving a coronal incision extending from one mastoid to the other exposing the cranium in each case. Maximum cranial length (MCL), maximum cranial breadth (MCB), bi-zygomatic breadth (BZB), minimum frontal breadth (MFB) and length of parietal chord (PC) were then measured. Stature was measured as the length of the body from head to heel in centimeters with the heel, buttocks, back of the shoulders and the head in contact with the autopsy table. Linear and stepwise multiple regression models were derived for estimation of stature from cranial measurements. Univariate, bivariate and multivariate regression models show statistically significant correlation between stature and the cranial measurements. The present study opines that the stature estimation from cranial dimensions using multivariate linear regression models is more accurate than those of the univariate and bivariate regression models. This study presents a rare data from Nepalese population that show typical Asian features and thus, is significant from anthropologic and genetic point of view. The study observations further contribute a baseline data bank for forensic pathologists and specialists.

Ulisses e Dionísio. Comentário e questionamento sobre a obra de Nietzsche "Origens da Tragédia"

Artigo publicado em 1904, no Almanaque Garnier. Nele, o autor procura abordar a estética do jovem Nietzsche de um ponto de vista histórico genético bastante amplo. Com essa abordagem, faz alguns questionamentos acerca das ideias de apolínio e dionisíaco.

Amyotrophic Lateral Sclerosis: A Genetic Point of View.

In the last twenty years the rapid advances in neurogenetic have revolutionized not only the molecular, pathological, inheritance but also the clinical concept of ALS. Here we review the current genetic breakthrough in familial and sporadic ALS, considering how this knowledge has allowed widening of the scenario on the possible pathogenic disease mechanisms and better understanding of the relationship between the genetic, pathological and clinical subtypes.

Population genetics ofCerastoderma edulein Ria Formosa (southern Portugal): the challenge of understanding an intraspecific hotspot of genetic diversity

Coastal lagoons are highly variable environments that may act as hotspots of genetic diversity as a consequence of their ecological role as nursery habitats of marine species with both ecological and fisheries importance. The edible cockle(Cerastoderma edule)is a commercially important shellfish resource inhabiting coastal lagoons in Europe and their fisheries management urgently needs genetic studies to design appropriate strategies to promote the recovery of exploited populations. The aim of this study was to assess theC. edulegenetic diversity and population structure at a small geographic scale, inside Ria Formosa coastal lagoon (southern Portugal) using mitochondrial cytochrome oxidase I sequences in six locations. Outcomes pointed to a common pattern of high haplotype diversity and non-significant genetic structuring inside the Ria Formosa lagoon. A high level of gene flow was detected between all localities and the presence of a single stock from a genetic point of view may be considered for fisheries management purposes. The existence of a high number of haplotypes and high values of haplotype diversity ofC. edulein Ria Formosa lagoon could be consistent with the hypothesis that higher genetic diversity is expected in populations occurring in coastal lagoons, suggesting that lagoons could increase standing genetic variation and an adaptive potential of lagoon populations as an ecological response to a highly variable environment.

Abstract 364: Mechanical properties of growing melanocytic nevi and the progression to melanoma

Abstract Melanocytic nevi are benign proliferations that sometimes turn into malignant melanoma in a way that is still unclear from the biochemical and genetic point of view. Diagnostic and prognostic tools are then mostly based on dermoscopic examination and morphological analysis of histological tissues. To investigate the role of mechanics and geometry in the morpholgical dynamics of melanocytic nevi, we study a computation model for cell proliferation in a layered non-linear elastic tissue. Numerical simulations show that the morphology of the nevus is correlated to the initial location of the proliferating cell starting the growth process and to the mechanical properties of the tissue. Our results also show that melanocytes are subject to compressive stresses that fluctuate widely in the nevus and depend on the growth stage. This result is important because mechanical stress has an effect that differs for primary and metastatic melanoma. We show experimentally that osmotic stress and collagen inhibit growth in primary melanoma cells while the effect is much weaker in metastatic cells. Knowing that morphological features of nevi might also reflect geometry and mechanics rather than malignancy could be relevant for diagnostic purposes. Citation Format: Alessandro Taloni, Alexander A. Alemi, Emilio Ciusani, James Sethna, Stefano Zaperi, Caterina Anna Maria Laporta. Mechanical properties of growing melanocytic nevi and the progression to melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 364. doi:10.1158/1538-7445.AM2014-364