Clinical Insights in RNA-Binding Protein Motif 20 Cardiomyopathy: A Systematic Review.

Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and heart transplantation (HTx), with genetic factors playing a significant role. In recent years, the RNA-binding protein motif 20 (RBM20), which affects the gene splicing of various proteins with different cellular functions, was identified as the first DCM gene with regulatory properties. Variants of RBM20 have been associated with severe forms of DCM. The aim of this critical systematic review was to analyse RBM20 cardiomyopathy clinical features and outcomes. According to PRISMA guidelines, a search was run in the PubMed, Scopus and Web of Science electronic databases using the following keywords: "RBM20"; "cardiomyopathy"; "arrhythmias"; "heart failure". A total of 181 records were screened, of which 27 studies were potentially relevant to the topic. Through the application of inclusion and exclusion criteria, eight papers reporting 398 patients with RBM20 pathogenic variants were analysed. The mean age at presentation was 41 years. Familiarity with cardiomyopathy was available in 59% of cases, with 55% of probands reporting a positive family history. Imaging data indicated a mild reduction of left ventricular ejection fraction (mean LVEF 40%), while tissue characterization was reported in 24.3% of cases, showing late gadolinium enhancement in 33% of patients. Composite outcomes of sustained monomorphic ventricular tachycardia or ventricular fibrillation occurred in 19.4% of patients, with 12% undergoing HTx. There were no gender differences in arrhythmic outcomes, while 96.4% of patients who underwent HTx were male. In conclusion, RBM20 cardiomyopathy exhibits a severe phenotypic expression, both in terms of arrhythmic burden and HF progression.

Genetic testing for hereditary cancer syndromes in Tunisian patients: Impact on health system.

INTRODUCTION: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings.

Genetic heterogeneity of familial hypercholesterolaemia in two populations from two different countries.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetically determined monogenic disorder of predominantly autosomal dominant inheritance. A number of studies on differences in the genetic profile of patients with FH have demonstrated the importance of a more substantive evaluation of genetic features. The aim of this study was to evaluate the genetic profile of patients with clinical FH among Italian and Russian patients. METHODS: We included 144 Italian and 79 Russian FH patients; clinical diagnosis was based on the same criteria. Patients were divided in: positive to genetic test (one causative variant), inconclusive (only variants of uncertain clinical significance [VUS]), and negative (with likely benign/benign variants, heterozygous variants in LDLRAP1 gene, or without causative variants). RESULTS: The genetic test was positive in 76.4 % of the Italian patients and in 49.4 % of the Russian patients. The presence of VUS alone was detected in 7.6 % and in 19.0 % (p < 0.001), respectively. Among patients with positive genetic diagnosis, pre-treatment LDL-C levels were higher in the Russian cohort (353.5 ± 111.3 vs. 302.7 ± 52.1 mg/dL, p = 0.009), as well as the percentage of treated patients (53.8 % vs. 14.5 %, p < 0.001) and the prevalence of premature coronary heart disease (12.8 % vs. 3.6 %, p = 0.039). Among patients carrying only VUS, mean pre-treatment LDL-C levels were similar between the cohorts (299.5 ± 68.1 vs. 295.3 ± 46.8 mg/dL, p = 0.863). Among pathogenic/likely pathogenic variants and VUS, only 5 % and 4 % was shared between the two cohorts, respectively. CONCLUSION: The genetic background of patients clinically diagnosed with FH in two different countries is characterized by high variability.

Expression profiles of human somatic mesenchymal stem cells derived from fresh endometrium, ectopic-endometrium and umbilical cord.

OBJECTIVES: The study investigated the stem cell expression profiles and differentiation capacities of mesenchymal stem cells (MSCs) from different tissues, specifically human eutopic endometrium MSCs (eut-MSCs), ectopic endometrium MSCs (ect-MSCs), and umbilical cord MSCs (UC-MSCs). Our aim was to identify any similarities in subpopulations among these MSCs and lay a foundation for MSCs repair. MATERIAL AND METHODS: MSCs were isolated from endometrial tissue (n = 5), endometriosis tissue (n = 6), and umbilical cords (n = 7). Flow cytometry was used to examine cell phenotype, and three lineage tests were conducted to evaluate the differentiation capacity of the MSCs. RESULTS: Eut-MSCs expressed CD44 (98.00 ± 0.96%), CD73 (99.54 ± 0.02%), CD140b (99.16 ± 0.50%), CD146 (93.87 ± 2.27%), SUSD2 (50.76 ± 8.15%), and CD271 (2.1 ± 1.22%). Ect-MSCs expressed CD44 (98.23 ± 1.60%), CD73 (99.63 ± 0.04%), CD140b (98.13 ± 0.53%), CD146 (93.88 ± 3.19%), SUSD2 (49.33 ± 6.36%), and CD271 (2.85 ± 1.17%). UC-MSCs expressed CD44 (99.11 ± ± 0.42%), CD73 (99.65 ± 0.12%), CD140b (99.84 ± 0.42%), CD146 (88.09 ± 4.20%), SUSD2 (72.87 ± 7.13%), and CD271 (6.19 ± 2.08%). The expression of SUSD2 and CD271 in UC-MSCs was slightly but not significantly higher than that in ect-MSCs and eut-MSCs. However, CD44, CD73, CD140b, and CD146 showed similar expression levels in UC-MSCs, ect-MSCs, and eut-MSCs. All three types of MSCs demonstrated the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. CONCLUSIONS: Our findings indicate that ect-MSCs, eut-MSCs, and UC-MSCs have similar stem cell phenotypes and the ability to differentiate into three lineages.

Here Is the Biology, Now What is the Mechanism? Investigating Biology Undergraduates' Mechanistic Reasoning within the Context of Biofilm Development.

Understanding molecular processes and coordinating the various activities across levels of organization in biological systems is a complicated task, yet many curricular guidelines indicate that undergraduate students should master it. Employing mechanistic reasoning can facilitate describing and investigating biological phenomena. Biofilms are an important system in microbiology and biology education. However, few empirical studies have been conducted on student learning of biofilms or how students utilize mechanistic reasoning related to systems thinking to explain biofilm formation. Using mechanistic reasoning and the theory of knowledge integration as conceptual and analytical frameworks, we examined the features of 9 undergraduate biology students' mechanistic models of a specific transition point in biofilm development. From these data, we constructed a model of knowledge integration in the context of biofilms, which categorizes students' knowledge based on features of their descriptions (e.g., entities, correct connections, and the nature of connections). We found that 4 of 9 students produced a fragmented model, 4 of 9 students produced a transitional model, and 1 student produced a connected model. Overall, students often did not discuss cell-cell communication mechanics in their mechanistic models and rarely included the role of gene regulation. Most connections were considered nonnormative and lacked important entities, leading to an abundance of unspecified causal connections. We recommend increasing instructional support of mechanistic reasoning within systems (e.g., identifying entities across levels of organization and their relevant activities) and creating opportunities for students to grapple with their understanding of various biological concepts and to explore how processes interact and connect in a complex system.

Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent.

The genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different intrinsic and/or extrinsic environments, can also result in different phenotypic outcomes, which can be missed in controlled laboratory studies. Natural wildlife populations, which capture both genotypic and environmental variability, provide an opportunity to more fully understand the phenotypic expression of genetic variation. We identified a synonymous polymorphism in the high-affinity Immunoglobulin E (IgE) receptor (GC and non-GC haplotypes) that has sex-dependent effects on immune gene expression, susceptibility to infection, and reproductive success of individuals in a natural population of field voles (Microtus agrestis). We found that the effect of the GC haplotype on the expression of immune genes differed between sexes. Regardless of sex, both pro-inflammatory and anti-inflammatory genes were more highly relatively expressed in individuals with the GC haplotype than individuals without the haplotype. However, males with the GC haplotype showed a stronger signal for pro-inflammatory genes, while females showed a stronger signal for anti-inflammatory genes. Furthermore, we found an effect of the GC haplotype on the probability of infection with a common microparasite, Babesia microti, in females - with females carrying the GC haplotype being more likely to be infected. Finally, we found an effect of the GC haplotype on reproductive success in males - with males carrying the GC haplotype having a lower reproductive success. This is a rare example of a polymorphism whose consequences we are able to follow across immunity, infection, and reproduction for both males and females in a natural population.

Informed Consent and Protection of Personal Data in Genetic Research on COVID-19.

The particular characteristics of COVID-19 demand the careful biomedical study of samples from patients who have shown different symptomatology, in order to understand the genetic foundations of its phenotypic expression. Research on genetic material from COVID-19 patients is indispensable for understanding the biological bases for its varied clinical manifestations. The issue of "informed consent" constitutes the crux of the problem in regulating research biobanks, because it concerns the relationship between the person and the parts separated from the body. There are several consensus models that can be adopted, varying from quite restricted models of specific informed consent to forms that allow very broad authorization (open consent). Our current understanding of COVID-19 is incomplete. Thus, we cannot plan, with precision, the research to be conducted on biological samples that have been, or will be, collected from patients infected by the novel coronavirus. Therefore, we suggest utilizing the "participation pact" between researchers and donors, based on a new form of participation in research, which offers a choice based on the principles of solidarity and reciprocity, which represent the communication of "values". In the last part of this paper, the general data protection regulation concerning the matter is discussed. The treatment of personal data must be performed with explicit goals, and donors must be provided with a clear, transparent explanation of the methods, goals and time of storage. The data must not be provided to unauthorized subjects. In conclusion, open informed consent forms will be necessary for research on individual patients and on populations.

Phenomics in sport: Can emerging methodology drive advanced insights?

Methodologies in applied sport science have predominantly driven a reductionist grounding to component-specific mechanisms to drive athlete training and care. While linear mechanistic approaches provide useful insights, they have impeded progress in the development of more complex network physiology models that consider the temporal and spatial interactions of multiple factors within and across systems and subsystems. For this, a more sophisticated approach is needed and the development of such a methodological framework can be considered a Sport Grand Challenge. Specifically, a transdisciplinary phenomics-based scientific and modeling framework has merit. Phenomics is a relatively new area in human precision medicine, but it is also a developed area of research in the plant and evolutionary biology sciences. The convergence of innovative precision medicine, portable non-destructive measurement technologies, and advancements in modeling complex human behavior are central for the integration of phenomics into sport science. The approach enables application of concepts such as phenotypic fitness, plasticity, dose-response dynamics, critical windows, and multi-dimensional network models of behavior. In addition, profiles are grounded in indices of change, and models consider the athlete's performance or recovery trajectory as a function of their dynamic environment. This new framework is introduced across several example sport science domains for potential integration. Specific factors of emphasis are provided as potential candidate fitness variables and example profiles provide a generalizable modeling approach for precision training and care. Finally, considerations for the future are discussed, including scaling from individual athletes to teams and additional factors necessary for the successful implementation of phenomics.

Clinicopathological characteristics of non-ampullary duodenal tumors and their phenotypic classification.

The tumorigenesis of non-ampullary duodenal epithelial tumors (NADETs) might be different between the oral and anal sides of Vater's papilla. We conducted an immunohistological review to elucidate the clinicopathological features according to the tumor location and phenotypic classification. A review of an institutional database identified 121 patients with 125 superficial NADETs. NADETs were histologically evaluated and classified into the intestinal or gastric type based on immunohistochemical analysis. Clinicopathological factors were compared based on the tumor location and phenotype. Logistic regression analysis was performed to identify independent predictors for gastric-type NADETs. According to location analysis, the mucin phenotype was significantly different (oral side, intestinal-type 64.8%, gastric-type 35.3%; anal side, intestinal-type 87.3%, gastric-type 12.7%; P < 0.01). Although the incidence of adenoma was significantly predominant in the intestinal type (75.3%), most gastric-type NADETs were cancerous (64.3%). Notably, most gastric-type NADETs were adenocarcinomas even when the tumor size was ≤0 mm. In multivariate analysis, tumor location on the oral side (odds ratio [OR], 4.42), villous structure (OR, 6.44), and low tumor gland density (OR, 9.49) were independent predictors of gastric-type tumors. Gastric-type NADETs significantly differ from intestinal-type NADETs in terms of tumor location, morphology, and biology.

Passage-dependent expression of STRO-1 in human gingival mesenchymal stem cells.

The expression of STRO-1, the essential mesenchymal stem cell marker, was found to decrease with advancing passages in few tissues. Because STRO-1 was identified and isolated from human gingiva, we were interested to know its status after a few passages. Human gingival mesenchymal stem cells (HGMSCs) were isolated from human gingiva. Flow cytometry was carried out with STRO-1, mesenchymal stem cell (MSC) positive marker CD73, and negative marker CD34/CD45. Samples were also subjected to CD90 and STRO-1 immunofluorescence staining. Gene expression was carried out for transcription factors OCT-4, NANOG, and NESTIN. The results showed a gradual decrease in STRO-1 and transcription factor expression with an increase in passage numbers. MSC positive marker CD73 was consistently expressed in all the passages. Negative markers were absent in all the passages. We conclude that STRO-1 may be a useful marker to isolate undifferentiated (potent) mesenchymal cells from gingiva.

Genetic Network Complexity Shapes Background-Dependent Phenotypic Expression.

The phenotypic consequences of a given mutation can vary across individuals. This so-called background effect is widely observed, from mutant fitness of loss-of-function variants in model organisms to variable disease penetrance and expressivity in humans; however, the underlying genetic basis often remains unclear. Taking insights gained from recent large-scale surveys of genetic interaction and suppression analyses in yeast, we propose that the genetic network context for a given mutation may shape its propensity of exhibiting background-dependent phenotypes. We argue that further efforts in systematically mapping the genetic interaction networks beyond yeast will provide not only key insights into the functional properties of genes, but also a better understanding of the background effects and the (un)predictability of traits in a broader context.

Contribution of the tRNAIle 4317A→G mutation to the phenotypic manifestation of the deafness-associated mitochondrial 12S rRNA 1555A→G mutation.

The 1555A→G mutation in mitochondrial 12S rRNA has been associated with aminoglycoside-induced and non-syndromic deafness in many individuals worldwide. Mitochondrial genetic modifiers are proposed to influence the phenotypic expression of m.1555A→G mutation. Here, we report that a deafness-susceptibility allele (m.4317A→G) in the tRNAIle gene modulates the phenotype expression of m.1555A→G mutation. Strikingly, a large Han Chinese pedigree carrying both m.4317A→G and m.1555A→G mutations exhibited much higher penetrance of deafness than those carrying only the m.1555A→G mutation. The m.4317A→G mutation affected a highly conserved adenine at position 59 in the T-loop of tRNAIle We therefore hypothesized that the m.4317A→G mutation alters both structure and function of tRNAIle Using lymphoblastoid cell lines derived from members of Chinese families (three carrying both m.1555A→G and m.4317A→G mutations, three harboring only m.1555A→G mutation, and three controls lacking these mutations), we found that the cell lines bearing both m.4317A→G and m.1555A→G mutations exhibited more severe mitochondrial dysfunctions than those carrying only the m.1555A→G mutation. We also found that the m.4317A→G mutation perturbed the conformation, stability, and aminoacylation efficiency of tRNAIle These m.4317A→G mutation-induced alterations in tRNAIle structure and function aggravated the defective mitochondrial translation and respiratory phenotypes associated with the m.1555A→G mutation. Furthermore, mutant cell lines bearing both m.4317A→G and m.1555A→G mutations exhibited greater reductions in the mitochondrial ATP levels and membrane potentials and increasing production of reactive oxygen species than those carrying only the m.1555A→G mutation. Our findings provide new insights into the pathophysiology of maternally inherited deafness arising from the synergy between mitochondrial 12S rRNA and tRNA mutations.

Sitting in the sun: Nest microhabitat affects incubation temperatures in seabirds.

During incubation parent birds are committed to a nest site and endure a range of ambient conditions while regulating egg temperatures. Using artificial eggs containing temperature loggers alongside ambient temperature (Ta) controls, incubation profiles were determined for four tropical seabird species at different nest site locations. Camera traps were used for ad-hoc behavioural incubation observations. Eggs experienced a range of temperatures during incubation and varied significantly between species and in some cases between different microhabitats within a species. Such variation has important consequences in the phenotypic expression of both physical and physiological traits of chicks, and ultimately species fitness. Exposed nest sites were more strongly correlated to Tas. Camera traps highlighted different incubation strategies employed by these species that could be related to trade-offs in predator defence, feeding habits, and temperature regulation of eggs. This study provides evidence that species with similar breeding habits could be affected by environmental stressors in similar ways and that the differences shown in nest site selection could negate some of these effects. We propose that habitats providing suitable nest microclimates will become increasingly important for the successful breeding of seabird species, particularly under predicted climate change scenarios.

Persistent pulmonary hypertension of the newborn: Advances in diagnosis and treatment.

Persistent pulmonary hypertension of the newborn (PPHN) is a frequent cause for admission to the neonatal intensive care unit and is associated with mortality and variable morbidities. It is primarily a state of oxygenation failure representing a failure of the normal postnatal decline in pulmonary vascular resistance that may be associated with right ventricular dysfunction. Enhanced knowledge of the pathophysiologic contributors to this syndrome helps clinicians understand its phenotypic expression and facilitates more focused intensive care decision-making. The approach to treatment should be based on alleviation of the elevation in pulmonary vascular resistance and should include optimization of lung recruitment and judicious use of pulmonary vasodilators. When response to inhaled nitric oxide is suboptimal, the physiologic contributors to impaired oxygenation need further investigation. Targeted neonatal echocardiography provides novel physiologic insights; in particular, it may help assess the adequacy of right ventricular performance, the relative contribution of the fetal shunts and the magnitude of the overall impairment to cardiac output. This information may facilitate therapeutic next steps and whether adjunctive vasodilators or drugs to augment ventricular function are preferable. This article provides a comprehensive overview of the pathological contributors to PPHN, the physiologic constituents of its phenotypic expression, standard approach to therapeutic intervention, and the role of bedside echocardiography in enhancing the decision-making process.

Features of Turner syndrome among a group of Cameroonian patients.

OBJECTIVE: To describe the features of Turner syndrome among a group of Cameroonian patients. METHODS: A descriptive cross-sectional study was conducted among patients with amenorrhea and/or short stature who attended the genetic unit of Yaoundé Gynecology, Obstetrics and Pediatric Hospital (Yaoundé, Cameroon) for a specialist consultation between July 1, 2007, and December 31, 2008. Sociodemographic, clinical, and cytogenetic data were collected. RESULTS: Turner syndrome was confirmed among 11 of the 14 participants (seven had monosomy of the X chromosome; four had mosaicism involving a structural abnormality of the second X chromosome). The mean age at diagnosis was 18.4±2.8years. The reasons for consultation were delayed puberty (n=10) and short stature (n=1). Nine patients had a short neck, nine had a forearm carrying-angle deformity, eight had a low hairline, and two had a webbed neck. Abdominal ultrasonography identified a horseshoe kidney in two patients and a rudimentary uterus in nine patients. None of the patients displayed cardiac abnormalities. Hypergonadotropic hypogonadism was reported among five patients. Eight patients did not receive hormonal treatment owing to advanced bone age or economic reasons. CONCLUSION: Late diagnosis and variable phenotypic expression were key features of Cameroonian patients with Turner syndrome.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: variable phenotypic expression in three affected sisters from Mexican ancestry.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal disease caused by mutations in genes for the tight junction transmembrane proteins Claudin-16 (CLDN16) and Claudin-19 (CLDN19). We present the first case report of a Mexican family with three affected sisters carrying a p.Gly20Asp mutation in CLDN19 whose heterozygous mother showed evident hypercalciuria and normal low magnesemia without any other clinical, laboratory, and radiological symptoms of renal disease making of her an unsuitable donor. The affected sisters showed variable phenotypic expression including age of first symptoms, renal urinary tract infections, nephrolithiasis, nephrocalcinosis, and eye symptoms consisting in retinochoroiditis, strabismus, macular scars, bilateral anisocoria, and severe myopia and astigmatism. End stage renal disease due to renal failure needed kidney transplantation in the three of them. Interesting findings were a heterozygous mother with asymptomatic hypercalciuria warning on the need of carefully explore clinical, laboratory, kidney ultrasonograpy, and mutation status in first degree asymptomatic relatives to avoid inappropriate kidney donors; an evident variable phenotypic expression among patients; the identification of a mutation almost confined to Spanish cases and a 3.5 Mb block of genomic homozygosis strongly suggesting a common remote parental ancestor for the gene mutation reported.

Phenotypic spectrum in uniparental disomy: Low incidence or lack of study?

CONTEXT: Alterations in the human chromosomal complement are expressed phenotypically ranging from (i) normal, via (ii) frequent fetal loss in otherwise normal person, to (iii) sub-clinical to severe mental retardation and dysmorphism in live births. A subtle and microscopically undetectable chromosomal alteration is uniparental disomy (UPD), which is known to be associated with distinct birth defects as per the chromosome involved and parental origin. UPD can be evident due to imprinted genes and/or activation of recessive mutations. AIMS: The present study comprises of data mining of published UPD cases with a focus on associated phenotypes. The goal was to identify non-random and recurrent associations between UPD and various genetic conditions, which can possibly indicate the presence of new imprinted genes. SETTINGS AND DESIGN: Data mining was carried out using the homepage "http://www.fish.uniklinikum-jena.de/UPD.html.", an online catalog of published cases with UPD. MATERIALS AND METHODS: The UPD cases having normal karyotype and with or without clinical findings were selected to analyze the associated phenotypes for each chromosome, maternal or paternal involved in UPD. RESULTS: Our results revealed many genetic conditions (other than the known UPD syndromes) to be associated with UPD. Even in cases of bad obstetric history as well as normal individuals chance detection of UPD has been reported. CONCLUSIONS: The role of UPD in human genetic disorders needs to be studied by involving larger cohorts of individuals with birth defects as well as normal population. The genetic conditions were scrutinized in terms of inheritance patterns; majority of these were autosomal recessive indicating the role of UPD as an underlying mechanism.

The concomitant occurrence of JAK2V617F mutation and BCR/ABL transcript with phenotypic expression - an overlapping myeloproliferative disorder or two distinct diseases? - case report.

The concomitant occurrence of JAK2617F mutation and BCR/ABL translocation is a rare event. It is unclear if this is a result of the clonal evolution or a separately emergence of two clones and if it could lead to the progression to a more aggressive phase of the disease. We present the case of a 61-year-old man diagnosed and treated for polycythaemia vera for 7 years, which evolved into chronic myeloid leukemia BCR/ABL positive and with JAK2617F mutated clone, that became dominant after an effective treatment with Imatinib.

Teaching neuroinformatics with an emphasis on quantitative locus analysis.

Although powerful bioinformatics tools are available for free on the web and are used by neuroscience professionals on a daily basis, neuroscience students are largely ignorant of them. This Neuroinformatics module weaves together several bioinformatics tools to make a comprehensive unit. This unit encompasses quantifying a phenotype through a Quantitative Trait Locus (QTL) analysis, which links phenotype to loci on chromosomes that likely had an impact on the phenotype. Students then are able to sift through a list of genes in the region(s) of the chromosome identified by the QTL analysis and find a candidate gene that has relatively high expression in the brain region of interest. Once such a candidate gene is identified, students can find out more information about the gene, including the cells/layers in which it is expressed, the sequence of the gene, and an article about the gene. All of the resources employed are available at no cost via the internet. Didactic elements of this instructional module include genetics, neuroanatomy, Quantitative Trait Locus analysis, molecular techniques in neuroscience, and statistics-including multiple regression, ANOVA, and a bootstrap technique. This module was presented at the Faculty for Undergraduate Neuroscience (FUN) 2011 Workshop at Pomona College and can be accessed at http://mdcune.psych.ucla.edu/modules/bioinformatics.

Pseudoxanthoma Elasticum: A Novel Mutation in the ABCC6 Gene That Affects Eye Manifestations of the Disease.

PURPOSE: To determine whether a correlation between ABCC6 mutations and ocular phenotypic expressions exists. METHODS: In this study, 28 relatives of a consultand with known pseudoxanthoma elasticum were recruited for evaluation of the ocular manifestations of the disease, including peau d'orange appearance, angioid streaks, choroidal neovascular membranes, peripapillary atrophy, and retinal drusen. Comprehensive eye examinations were documented for all patients, who were then evaluated for the presence of known mutations in the aforementioned ABCC6 gene. RESULTS: Statistically significant correlations were noted between the gene and peau d'orange appearance (P  =  0.0016), angioid streaks (P < 0.0001), and choroidal neovascular membranes (P  =  0.0016). CONCLUSIONS: A statistically significant association was documented between the R39G mutation of the ABCC6 protein and 3 of 6 known manifestations of pseudoxanthoma elasticum. Although mutations of this gene are clearly associated with angioid streaks, the mechanism by which the transporter affects development of this pathology is speculative.