Degree Of Phenotypic Variation Research Articles

Grain quality indicators and their phenotypic variability of ancient varieties of Triticum aestivum in the mountains of Uzbekistan

Abstract. Ruziyev F, Djabbarov I, Olimjonova S, Niyozov U, Urokov S, Ishankulova D, Bakhadirov U. 2023. Grain quality indicators and their phenotypic variability of ancient varieties of Triticum aestivum in the mountains of Uzbekistan. Biodiversitas 24: 5995-6001. Today, creation of varieties of agricultural crops that are resistant to adverse environmental factors and produce stable crops under the influence of stress factors has become one of the most important issues in the world. In the following years, scientific and research work is being carried out on the wide use of the diversity of its genetic resources in the creation of new varieties of wheat (Triticum aestivum L.). In this regard, there are opportunities to use wild, semi-wild and ancient local forms of wheat with high protein and high gluten content to create varieties that meet modern production requirements. Therefore, it is important to evaluate the quality indicators of ancient varieties and the degree of phenotypic variation in the selection of wheat varieties that are resistant to adverse environmental factors, fertile and high-quality. This research work, aimed at researching ancient wheat varieties cultivated by the people living in the mountainous regions of Uzbekistan for many years. According to the research results, the grain quality indicators (grain hardness, diameter of grains, grain quality indicators, rheological properties, etc.) of the ancient wheat varieties distributed in the mountain regions are different. According to the results of the experiment, the grain hardness of the studied ancient wheat varieties is 73-82 µm, grain diameter 2.65-2.71 mm, hectolitre of weight 818.2-838.1±8.7 g/L, vitreousness 62.2-70.3%, gluten content in grain 31.5-34.6%, sedimentation index 64.4-77.2 mL. It was also observed that the phenotypic variability of the quality indicators was different in the wheat varieties that were the object of the study. Differences in the grain quality indicators of ancient wheat varieties are explained by the different effects of climatic parameters, abiotic and biotic factors in the regions where wheat grows. The information presented in the article provides an opportunity to select ancient wheat varieties distributed in the mountainous regions of Uzbekistan as starting sources for the creation of varieties with high nutritional value, resistant to adverse factors.

Geological Substrate Effects on Teucrium montanum L. (Lamiaceae) Morphological Traits: Geometric Morphometrics Approach.

The shape-environment relationship in plants refers to the ways in which the physical characteristics and structures of plants are influenced by their environment. Plants have evolved a remarkable ability to adapt to their specific habitats, and their shape and form play a crucial role in determining their survival and reproductive success. This study aimed to examine differences in size and shape between morphological traits in mountain germander (Teucrium montanum L.) from different geological substrates (calcareous and serpentinite). For this study, 400 individuals of T. montanum from 20 populations (ten populations from the serpentinite and ten from the calcareous substrate) were selected. Using the geometric morphometrics approach, it was shown that the degree of phenotypic variation in the size and shape of the corolla, leaf, and stem of T. montanum depends on the type of substrate. The main differences between the populations are the narrower part of the lower lip of the corolla, the narrower leaf, and the wider central part of the vascular system stem from serpentinite populations. The results of this study will contribute to a better understanding of the morphological variability of T. montanum in relation to edaphic conditions. In addition, the results confirm that certain morphological differences play an important role in the adaptive response in relation to substrate composition, especially for substrates with increased metal content, such as serpentinite. The shape-environment relationship in plants could define diversity and complexity in plant life, and underscores the importance of shape as a key factor in their survival and success in different habitats.

Rapid signaling reactivation after targeted BRAF inhibition predicts the proliferation of individual melanoma cells from an isogenic population

Cancer cells within tumors display a high degree of phenotypic variability. This variability is thought to allow some of the cells to survive and persist after seemingly effective drug treatments. Studies on vemurafenib, a signaling inhibitor that targets an oncogenic BRAF mutation common in melanoma, suggested that cell-to-cell variation in drug resistance, measured by long-term proliferation, originates from epigenetic differences in gene expression that pre-exist treatment. However, it is still unknown whether reactivation of signaling downstream to the inhibited BRAF, thought to be a key step for resistance, is heterogeneous across cells. While previous studies established that signaling reactivation takes place many hours to days after treatment, they monitored reactivation with bulk-population assays unsuitable for detecting cell-to-cell heterogeneity. We hypothesized that signaling reactivation is heterogeneous and is almost instantaneous for a small subpopulation of resistant cells. We tested this hypothesis by monitoring signaling dynamics at a single-cell resolution and observed that despite highly uniform initial inhibition, roughly 15% of cells reactivated signaling within an hour of treatment. Moreover, by tracking cell lineages over multiple days, we established that these cells indeed proliferated more than neighboring cells, thus establishing that rapid signaling reactivation predicts long-term vemurafenib resistance.

How to become a crab: Phenotypic constraints on a recurring body plan.

A fundamental question in biology is whether phenotypes can be predicted by ecological or genomic rules. At least five cases of convergent evolution of the crab-like body plan (with a wide and flattened shape, and a bent abdomen) are known in decapod crustaceans, and have, for over 140 years, been known as "carcinization." The repeated loss of this body plan has been identified as "decarcinization." In reviewing the field, we offer phylogenetic strategies to include poorly known groups, and direct evidence from fossils, that will resolve the history of crab evolution and the degree of phenotypic variation within crabs. Proposed ecological advantages of the crab body are summarized into a hypothesis of phenotypic integration suggesting correlated evolution of the carapace shape and abdomen. Our premise provides fertile ground for future studies of the genomic and developmental basis, and the predictability, of the crab-like body form.

Ventajas y límites de la variabilidad morfofisiológica para el establecimiento, la colonización y la expansión del bivalvo invasor Limnoperna fortunei en Sudamérica

Phenotypic variability, both based on phenotypic plasticity and genetic diversity, can be a main factor affecting the invasion process of alien species. Limnoperna fortunei (Dunker 1857) was introduced in South America around 1990, in the Río de la Plata estuary, Argentina, from where it spread swiftly to cover most of the basin and other smaller watersheds. However, some environments have not been colonized and, presumably, the survival of this species was affected by different environmental factors such as suspended solids, salinity, and pollution. L. fortunei showed high genetic and morphological variability, showing a distribution strongly affected by human activities and its dispersal vectors. The degree of phenotypic variability would be playing a main role in its establishment, or not, in the different environments. Morphological and metabolic variations, including changes in the growth rate, development of internal organs or changes in the rate of filtration and respiration in border areas of its distribution or under extreme environmental conditions, would allow to explain, together with other variables such as the presence of dispersal vectors, the current distribution pattern.

Hybrid forms of mandarin (Citrus reticulata blanco var. Unchiu tan.) from interspecific crosses and their characteristics

Representatives of the genus Citrus L., which includes C. limon, C. sinensis, C. reticulata, C. paradisi, C. maxima, C. medica, C. aurantifolia and other species are the most important fruit crops in countries with subtropical and tropical climates. Cross-pollination, variability of sexual offspring fixed by apomixis, preserved during vegetative propagation contributed to the appearance of intergeneric and interspecific hybrids combining characters and properties of different species. The aim of this work was to carry out interspecific crosses to create biodiversity of Citrus reticulata Blanco var. unchiu Tan. and create new forms with breeding valuable traits. Six interspecific combinations of crossings with the involvement of different varieties were carried out, and a large variety of seedlings was obtained. In sexual offspring from interspecific crosses, a high degree of phenotypic variability is observed on the leaf blade, in shape, size, color of the fruit, thickness and separability of the peel, the presence and absence of seeds, as well as organoleptic properties. All these characteristics represent important criteria for the variety. According to the totality of morphological characters, 24 promising forms were selected. The combination of C. reticulata × C. maxima crossing is the most productive, which allowed us to identify the largest number of forms with breeding valuable traits. Forms Yub - P Nmik; Yub – P Nmik - 1; MV - P Azah; MV - P Azah - 1; MV - P Azah - 2; Kr - P Azah; Cr - P Azah – 1 are promising and are important for the creation of new large-fruited varieties of mandarin. From combination of crossbreeding with C. sinensis such forms as KV - ApV, KV-ApV-2, MV-ApV-1were identified, characterized by large-fruited, fruits with high organoleptic properties. Hybrids bred with C. medica, C. aurantifolia, C. limon meyer are important for creating citrus biodiversity with valuable traits.

ENDOSYMBIONTS OF ENTOMOPATHOGENIC NEMATODES FROM SOUTH ITALY: A PHENOTYPIC STUDY

We examined different Xenorhabdusstrains (five of X. bovieniiand two of X. kozodoii), obtained from EPNisolates belonging to the genus Steinernema(S. feltiae, S. ichnusae, S. apuliae, S. vulcanicum) of different geographicorigin by both genotypic and phenotypic analysis. Common laboratory assays were done for traits such as antibioticresistance, haemolytic activity, lactose utilisation, biofilm production, chosen as the least selectable traits for EPN life-cycle, and thus as (presumably) neutral traits. As selective marker, the activity of the endosymbiont’s toxins was verified inan in vivoassay on G. mellonellalarvae. Genotyping done by 16S partial sequencing was used for identification purposes.Xenorhabdusbovieniiisolates showed a broad phenotypic spectrum; on the other hand, X. kozodoiishowed a less degreeof phenotypic variation, reduced ability of biofilm production and conspicuous β-galactosidase activity. However, all thestrains were able to kill G. mellonellalarvae with high efficiency.

The degree of phenotypic variation of morphological and agronomic characters of eight F1 populations of cassava (Manihot esculenta) at Bandar Lampung

Utomo SD, Yusartika P, Popy L, Edy A, Sunyoto, Ardian. 2018. The degree of phenotypic variation of morphological and agronomic characters of eight F1 populations of cassava (Manihot esculenta) at Bandar Lampung. Pros Sem Nas Masy Biodiv Indon 4: 39-46. The objective of this study was to estimate the degree of phenotypic variation (DPV) of morphological and agronomic characters of eight F1 populations of cassava the results of natural sexual hybridization and/or self of 80 parental clones; the eight populations was derived from female parents UJ 5, Cimanggu, UJ 3, Klenteng 37, Mulyo 3, BL1, BL 4 and Darul Hidayah. The pollination was conducted in 2015 at highland Sekincau, West Lampung (1100 m asl.). The morphological and agronomic characters included qualitative and quantitative characters. Study to estimate the was conducted at Bandar Lampung, from May 2016-March 2017. The DPV of quantitative characters were high if the percentage of recombinant phenotypes > 67%, moderate if 33%≤DPV≤67, and low if DPV 2 x Interquartile Range (IQR) dan low if the total Range ≤ 2 x IQR. Quantitative characters color of apical leaves, color of adaxial petiole, and color of abaxial petiole of all populations showed DPV high or moderate. All quantitative characters observed (number of leaf lobus, length of leaf lobus, width of leaf lobus, length/width ratio of leaf lobus, length of petiole, and starch rendement) indicated DPV high on F1 half-sib population of UJ5, UJ3, BL1, dan BL4. Except for the length of leaf lobus and starch rendement, all quantitative characters showed high DPV on population of Cimanggu and Darul Hidayah; DPV of length of leaf lobus and starch rendement was low. The high variation of most qualitative and quantitative characters indicated that the open/natural hybridization among parental clones occurred and was effective to produce recombinant phenotypes.

F39. Parsonage from a power tool: An unusual presentation of neuralgic amyotrophy in a 78 year old woman after using a chainsaw

Introduction A 78 year old Caucasian female presented for an electrodiagnostic (EDX) evaluation for right hand weakness and atrophy. Symptoms began 3 months prior one day after she was working with a chainsaw in the backyard and experienced severe right scapular pain followed by a monophasic course of progressively worsening weakness, inability to grip things such as a pen or coffee cup, and numbness and tingling into digits 1–3. Exam showed right sided prominent atrophy of the first dorsal interosseous (FDI) and thenar eminence, 4/5 strength in shoulder abduction and elbow flexion/extension, 3/5 strength in finger flexion and abduction, a positive okay sign, diminished sensation throughout the right upper limb. She also has weakness of the serratus anterior with mild medial winging of the right scapula during anteflexion. Myelogram and computed tomography showed no significant neural compression to explain patient’s symptoms, specifically no C8 compression. Methods The patient underwent EDX testing and a neuromuscular ultrasound. Results Nerve conduction studies showed prolonged distal onset latency and reduced amplitude of the right median motor nerve and no response in the right ulnar motor nerve, but were otherwise normal. Needle evaluation of the right FDI muscle showed reduced insertional activity with no recruitment of motor units, and the right pronator quadratus muscle showed reduced recruitment. Neuromuscular ultrasound of the right brachial plexus showed some increased hypoechogenicity and possible increased caliber compared to the left. The right forearm musculature including the pronator quadratus and FDI demonstrated increased hyperechogenicity and atrophy consistent with chronic denervation. Patient was diagnosed with a distal predominant neuralgic amyotrophy (NA) variant. Conclusion Neuralgic amyotrophy (NA), also known as Parsonage-Turner Syndrome, exhibits a high degree of phenotypic variability with only two-thirds of patients presenting with the classic phenotype with its predilection for the superior trunk of the brachial plexus. In this case, the patient met 5/5 of the clinical criteria for NA as defined by Van Alfen and neuromuscular ultrasound was helpful in further confirming the diagnosis. NA should be considered in patients even if they do not fit the classic phenotype of predominately proximal arm weakness and ultrasound of the plexus and affected muscles can be a helpful adjunctive diagnostic tool is such cases which do not “fit the textbook.”

Abstract 772: The molecular landscape of dermal neurofibromatosis

Abstract Background: Neurofibromatosis type I (NF1) is a genetic disorder that disrupts neurological tissue growth and can lead to a diverse set of symptoms including systematic growth of benign tumors, learning disorders and bone deformities. It is a rare disease occurring in only 1 in 3,000 people worldwide. While the disease has been linked to loss of function in the NF1 gene - a known tumor suppressor - there is a high degree of phenotypic diversity in the NF1 patient population, making it difficult to identify the underlying cause of the disease and treat it effectively. In this work we seek to improve overall knowledge of dermal NF1 through global molecular characterization of the disease. Methods: We have collected four dermal neurofibromas and peripheral blood from each of 11 NF1 patients. We analyzed each sample using (1) Whole genome sequencing (WGS) on the Illumina HiSeq X platform, (2) Illumina OMNI2.5 Arrays (3) RNA-Sequencing on an Illumina HiSeq v4 machine and (4) iTRAQ-labeled proteomics. WGS data for both tumor and blood samples from each patient were used to identify patient-specific germ-line mutations as well as tumor-specific somatic mutations in each sample. Single nucleotide polymorphisms identified by the OMNI Arrays were used to identify copy number alterations in both blood and tumor samples. RNA-Seq data and proteomics data were mapped to transcripts and proteins respectively. Results: Preliminary analysis of this data illustrates a diverse genomic landscape of NF1. Hierarchical clustering of copy number alterations largely show samples clustering by tissue, suggesting that most copy number alterations are somatic and not shared across the germline. However, there are two patients that show germline copy number alterations, including one patient with loss in the NF1 region. WGS analysis suggests similar diversity with each patient possessing a distinct combination of germline and somatic mutations of NF1 and other cancer-related genes. Cluster analysis of the RNA-Seq data shows no patient-specific clusters, suggesting that that each tumor executes a unique transcriptional program. Conclusion: This work represents a first-ever attempt to profile the diversity of dermal neurofibromatosis at a molecular level. Preliminary analysis of the data underscores the complexity of this disease and explains, in part, previous difficulty in identifying effective treatments. Ongoing work includes expanding the analysis to include more patient samples and other types of NF1-derived tumors. As an orphan disease, NF1 has been poorly characterized compared to more common cancers. To rectify this, the Children's Tumor Foundation and Sage Bionetworks are collaborating to make NF1 data available to the public to accelerate research and the drug discovery pipeline. We expect that this data will be a resource for other NF1 researchers to assist in the study of this disease at the molecular level. All data and preliminary results are publicly available at http://www.synapse.org/dermalNF Citation Format: Sara JC Gosline, Pamela Knight, Thomas Yu, Nripesh Prasad, Angela Jones, Shristi Shrestha, Braden Boone, Shawn E. Levy, Andrew J. Link, Allison C. Galassie, Hubert Weinberg, Stephen Friend, Salvatore La Rosa, Justin Guinney, Annette Bakker. The molecular landscape of dermal neurofibromatosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 772.

CE: Nursing Management of Patients with Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS), a hereditary connective tissue disorder, has historically been misunderstood and underdiagnosed by health care providers. Because of the high degree of phenotypic variability, patients are often correctly diagnosed only after years of seemingly unrelated but debilitating injuries and illnesses. Specific genetic mutations have been identified for some, but not all, EDS types; patients presenting with a high index of suspicion should be referred to a geneticist. As awareness and recognition of the syndrome improve, nurses are increasingly likely to care for patients with EDS. This article gives a brief overview of the syndrome and provides guidance on ways to manage symptoms, recognize and prevent serious complications, and improve patients' quality of life.

Genital and body allometry in two species of noctuid moths (Lepidoptera: Noctuidae)

One-size-fits-all and related hypotheses predict that static allometry slopes for male genitalia will be consistently lower than 1.0 and lower than the slopes for most other body parts (somatic traits). We examined the allometry of genitalic and somatic morphological traits in males and females of two species of noctuid moths, Spodoptera exigua (Hubner, [1808]) and Helicoverpa armigera (Hubner, [1808]). The relationship between genitalic traits and body size was generally strongly negative-allometric in males but with no significant differences from 1.00 in females of the two species examined. However, in females, the slope of genital traits was also lower than the slopes for somatic traits. The relationship between somatic traits and the body size indicator was approximately isometric in most cases in males, except in four traits in S. exigua, in which the slopes showed slight negative allometry, and the hind tibia in H. armigera, in which the slope had positive allometry. However, in females, some somatic traits showed isometric and some other showed negative allometry in both species. The coefficients of variation (CV) for all structures in the males were low, not exceeding 10%. Genitalic traits showed significantly lower CV than somatic traits in males. In females, somatic traits showed lower CV than genitalic traits but with no significant difference in the H. armigera. Our observations of strongly negative allometry for genitalic traits in males are consistent with stabilizing selection on genital size and we suggest that male performance in interactions with females is the source of selection on male genital allometry. The difference in the degree of phenotypic variation between genitalic and somatic traits in the two studied species is attributed to the different developmental-genetic architectures of these traits. Female genitalia showed a similar trend to the males, although the difference between genital and somatic traits was not significant in females. This finding suggests that selection is acting differently on male and female genitalia. Positive allometry of hind tibia in H. armigera may be a result of secondary sexual function.

A Bayesian model for the analysis of transgenerational epigenetic variation.

Epigenetics has become one of the major areas of biological research. However, the degree of phenotypic variability that is explained by epigenetic processes still remains unclear. From a quantitative genetics perspective, the estimation of variance components is achieved by means of the information provided by the resemblance between relatives. In a previous study, this resemblance was described as a function of the epigenetic variance component and a reset coefficient that indicates the rate of dissipation of epigenetic marks across generations. Given these assumptions, we propose a Bayesian mixed model methodology that allows the estimation of epigenetic variance from a genealogical and phenotypic database. The methodology is based on the development of a T matrix of epigenetic relationships that depends on the reset coefficient. In addition, we present a simple procedure for the calculation of the inverse of this matrix (T−1) and a Gibbs sampler algorithm that obtains posterior estimates of all the unknowns in the model. The new procedure was used with two simulated data sets and with a beef cattle database. In the simulated populations, the results of the analysis provided marginal posterior distributions that included the population parameters in the regions of highest posterior density. In the case of the beef cattle dataset, the posterior estimate of transgenerational epigenetic variability was very low and a model comparison test indicated that a model that did not included it was the most plausible.

Targeting the Adaptability of Heterogeneous Aneuploids

Aneuploid genomes, characterized by unbalanced chromosome stoichiometry (karyotype), are associated with cancer malignancy and drug resistance of pathogenic fungi. The phenotypic diversity resulting from karyotypic diversity endows the cell population with superior adaptability. We show here, using a combination of experimental data and a general stochastic model, that the degree of phenotypic variation, thus evolvability, escalates with the degree of overall growth suppression. Such scaling likely explains the challenge of treating aneuploidy diseases with a single stress-inducing agent. Instead, we propose the design of an "evolutionary trap" (ET) targeting both karyotypic diversity and fitness. This strategy entails a selective condition "channeling" a karyotypically divergent population into one with a predominant and predictably drugable karyotypic feature. We provide a proof-of-principle case in budding yeast and demonstrate the potential efficacy of this strategy toward aneuploidy-based azole resistance in Candida albicans. By analyzing existing pharmacogenomics data, we propose the potential design of an ET against glioblastoma.

Revisiting the work of Maurice Goldenhar—an overview of Goldenhar syndrome

Goldenhar syndrome is a heterogeneous disorder resulting in craniofacial and vertebral malformations. Due to its low prevalence and extreme phenotypic variation, there is limited published literature on the disorder. The aim of this paper is to provide an updated review of the literature in order to improve awareness of Goldenhar syndrome and to guide physicians in their diagnosis and treatment plans. Goldenhar syndrome is a multifactorial disorder with most cases being sporadic, though autosomal dominant and autosomal recessive cases have been reported. Due to the high degree of phenotypic variation, Goldenhar syndrome is considered to be part of the oculo-auriculo-vertebral spectrum. Although there are no minimal diagnostic criteria, patients typically present with varying degrees of microtia, ear tags, craniofacial microsomia, eye anomalies, and diverse vertebral anomalies. For optimal outcomes, a multidisciplinary approach is required to best address ocular, auricular, vertebral, craniofacial, dental, and psychological manifestations. This paper reviews the etiology, risk factors, screening procedures, clinical features, and treatment for Goldenhar syndrome in order to aid in the early diagnosis of affected individuals and improve treatment outcomes.

Evaluation of Phenotypic Diversity by Use of Variable Analysis Multi of Various Populations of Oak Cork (<i>Quercus suber</i> L.) in Tunisia

Populations of oak cork (Quercus suber L.) originated from different areas in Tunisia were analysed based on morphological characters to assess the overall degree of phenotypic variability, to detect similarities between the genotypes and to evaluate significant forest features. One-way ANOVA analysis shows a significant difference between oak cork populations and demonstrates that parameters measured on leaves show an important degree of variability and permit to discriminate oak cork individuals. Vegetative variables are leaf length, leaf width, petioles length, number of leaf veins, petioles width, spines number, leaf area, length nipples, diameter nipples, weight nipples, and height trees. Diameter trees were scored and subjected to multivariate analysis. Results showed a considerable diversity among local germoplasme of oak cork. Principal component analysis (PCA) revealed that the characters related to the length and width of the sheets and the nipples accounted for a large proportion of the observed variability. Cluster analysis showed a typically continuous phenotypic diversity among oak cork accessions, and little asso-ciations between accessions from same geographic origin. Also, some heterogeneity within accessions that received the same denomination was evidenced. The variability observed between different populations is attached to phenotypic characters which depend primarily on two factors, gene and environment.

Autism and Schizophrenia Are Disorders of Evolvability

Autism and schizophrenia are of particular interest because new developments in genomic medicine address three aspects of the conditions that have been difficult, thus far, to resolve: their heterogeneity, from subclinical manifestations to disorders that are gravely disabling; the genetic basis for their high heritability; and the persistence of disorders in light of their high heritability but low reproductive success they convey. The origins of autism and schizophrenia, their persistence and heterogeneity can be understood by integrating information from genomic science, the social brain and the evolution of socialization, intelligence and language. Both conditions are associated with structural changes in the genome, specifically copy number variants. Such systemic mutations contribute to an unstable and mutable genome and have been especially notable during primate > hominid evolution. Along with mechanisms that affect gene expression, they contribute to a genome characterized by variability and evolvability. A dynamic and variable genome is reflected by a high degree of phenotypic variation. This, in turn, is reflected in the diversity of neurodevelopmental disorders, in particular autism and schizophrenia. Evolvability is more than a dispositional concept, it is a trait in its own right. In the special case of hominid evolution, evolvability has been both an independent and a dependent variable. Evolution of the modern human brain seems to have arisen during the cultivation of unstable regions in the genome that were conducive to a high degree of inter-individual and inter-generational variation. The consequence of even small aberrations in evolutionary processes and phenotypic variations is most likely to be manifest in the functions of the social brain: self-referential processing, perspective taking and the dual components of empathy; also language as well as intelligence itself. The trade-off is a dynamic genome that can rearrange itself in untoward ways and may be felt in one or more of the above functions. The occurrence of neurodevelopmental disorders ranging from the learning disabilities and ADD to autism and schizophrenia, are epiphenomenal to a genome that is unstable and mutable. The selective advantage of such a genome is the runaway evolution of positive prosocial and intellective traits. If there is a core to the pathology that emerges in autism and schizophrenia, it is at the genomic level, and is probably related to the unique evolvability of the human genome. Genetic transformation as an agent of evolvability is necessarily associated with untoward consequences. Just as point mutations may have deleterious effects, so do genomic transformations. The neurodevelopmental disorders, therefore, are the consequence of evolvability.

Genetic models of schizophrenia and related psychotic disorders: progress and pitfalls across the methodological “minefield”

The challenge of modelling a complex and multifaceted disorder such as schizophrenia is epitomised by the considerable degree of phenotypic variability described in patients and by the absence of specific and consistent neuropathological biomarkers. The pattern and severity of a range of clinical features, including florid psychotic symptoms such as hallucinations and delusions, negative symptoms and cognitive dysfunction, together with age at onset, course of illness and other indices, can vary greatly between individual patients. The undefined nature of the relationship between diagnosis and underlying aetiology has complicated research in the field of clinical and preclinical neuroscience, thereby making it difficult to generate or evaluate appropriate disease models of schizophrenia. In the present review, we explore those conceptual and practical issues that relate specifically to the genetic modelling of schizophrenia and related disorders in rodents. Practical issues that impact on the robustness of endophenotypic findings and their translational relevance are discussed with reference to evidence from selective genetic models of candidate risk genes and copy number variants implicated in schizophrenia.

An extended multi-locus molecular typing schema for Streptococcus pneumoniae demonstrates that a limited number of capsular switch events is responsible for serotype heterogeneity of closely related strains from different countries

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular serotype and through a Multi-Locus Sequence Typing schema (MLST) based on the sequencing of seven housekeeping genes. However, strains with a defined allelic profile (Sequence Type, ST) can have different serotypes, suggesting that the micro-evolution of the MLST lineages leads to a considerable degree of phenotypic variability. To better investigate the genetic diversity within these lineages, we set-up and then validated an extended molecular typing schema (96-MLST) based on the sequencing of ninety-six genomic loci. 96-MLST loci were designed within core-genes in a collection of 39 complete genomes of S. pneumoniae. None of the capsular genes was included in the schema. When tested on a collection of 69 isolates, 96-MLST was able to partition strains with the same ST and diverse serotypes into groups that were homogenous for capsular serotype, improving our understanding of the evolution of epidemiologically relevant lineages. Phylogenetic sequence analysis showed that the capsular heterogeneity of three STs that were sampled more extensively could be traced back to a limited number of capsular switch events, indicating that changes of serotype occur occasionally during the short term expansion of clones. Moreover, a geographical structure of ST156 was identified, suggesting that the resolution guaranteed by this method is sufficient for phylogeographic studies. In conclusion, we showed that an extended typing schema was able to characterize the expansion of individual lineages in a complex species such as S. pneumoniae.

Analysis of Large Phenotypic Variability of EEC and SHFM4 Syndromes Caused by K193E Mutation of the TP63 Gene

EEC (ectrodactyly, ectodermal dysplasia, clefting; OMIM 604292) is an autosomal dominant developmental disorder resulting mainly from pathogenic mutations of the DNA-binding domain (DBD) of the TP63 gene. In this study, we showed that K193E mutation in nine affected individuals of a four-generation kindred with a large degree of phenotypic variability causes four different syndromes or TP63-related disorders: EEC, Ectrodactyly-ectodermal dysplasia (EE), isolated ectodermal dysplasia, and isolated Split Hand/Foot Malformation type 4 (SHFM4). Genotype-phenotype and DBD structural modeling analysis showed that the K193-located loop L2-A is associated with R280 through hydrogen bonding interactions, while R280 mutations also often cause large phenotypic variability of EEC and SHFM4. Thus, we speculate that K193 and several other DBD mutation-associated syndromes may share similar pathogenic mechanisms, particularly in the case of the same mutation with different phenotypes. Our study and others also suggest that the phenotypic variability of EEC is attributed, at least partially, to genetic and/or epigenetic modifiers.