The FGF14 GAA repeat expansion in Greek patients with late-onset cerebellar ataxia and an overview of the SCA27B phenotype across populations.

A pathogenic GAA repeat expansion in the first intron of the fibroblast growth factor 14 gene (FGF14) has been recently identified as the cause of spinocerebellar ataxia 27B (SCA27B). We herein screened 160 Greek index cases with late-onset cerebellar ataxia (LOCA) for FGF14 repeat expansions using a combination of long-range PCR and bidirectional repeat-primed PCRs. We identified 19 index cases (12%) carrying a pathogenic FGF14 GAA expansion, a diagnostic yield higher than that of previously screened repeat-expansion ataxias in Greek LOCA patients. The age at onset of SCA27B patients was 60.5 ± 12.3 years (range, 34-80). Episodic onset (37%), downbeat nystagmus (32%) and vertigo (26%) were significantly more frequent in FGF14 expansion-positive cases compared to expansion-negative cases. Beyond typical cerebellar signs, SCA27B patients often displayed hyperreflexia (47%) and reduced vibration sense in the lower extremities (42%). The frequency and phenotypic profile of SCA27B in Greek patients was similar to most other previously studied populations. We conclude that FGF14 GAA repeat expansions are the commonest known genetic cause of LOCA in the Greek population and recommend prioritizing testing for FGF14 expansions in the diagnostic algorithm of patients with LOCA.

Revisiting the evolution of the Hippocratic Oath in obstetrics and gynecology.

Hippocrates, an influential figure in ancient Greek medicine, is best known for his lasting contribution, the Hippocratic Oath, which includes a significant message about obstetrics and gynecology. Given the Oath's status as a widely regarded ethical code for medical practice, it requires critical evaluation. The message of the Oath, as it related to obstetrics and gynecology, is expressed in ancient Greek by the phrase "οὐδὲ γυναικὶ πεσσὸν φθόριον δώσω" which translates directly to "I will not give to any woman a harming pessary." The words fetus and abortion were not present in the original Greek text of the Oath. Yet, this message of the Hippocratic Oath has been interpreted often as a prohibition against abortion. In this article, we present a critical linguistic and historical analysis and argue against the notion that the Hippocratic Oath was prohibiting abortion. We provide evidence that the words "foetum" (fetus) and "abortu" (abortion) were inserted in the Latin translations of the Oath, which then carried on in subsequent English versions. The addition of the words "fetus" and "abortion" in the Latin translations significantly altered the Oath's original meaning. Unfortunately, these alterations in the translation of the Hippocratic Oath have been accepted over the years because of cultural, religious, and social reasons. We assert that because the original Hippocratic Oath did not contain language related to abortion, it should not be construed as prohibiting it. The interpretation of the Oath should be based on precise and rigorous translation and speculative interpretations should be avoided.

Testing the accuracy of the DRNNAGE software for age estimation in a modern Greek sample.

Estimation of age-at-death from human skeletal remains is fundamental in forensic anthropology as part of the construction of the biological profile of the individual under study. At the same time, skeletal age-at-death estimation in adults is problematic due to the disparity between chronological and biological age, the important inter-individual variability at the rate of skeletal aging, and inherent biases in the available methodologies (e.g., age mimicry). A recent paper proposed a method for skeletal age-at-death estimation based on multiple anatomical traits and machine learning. A software was also created, DRNNAGE, for the easy implementation of this method. The authors of that study supported that their methods have very high repeatability and reproducibility, and the mean absolute error of the age estimation was ~6 years across the entire adult age span, which is particularly high and promising. This paper tests the proposed methodology on a modern documented Greek sample of 219 adult individuals from the Athens Collection, with age-at-death from 19 to 99 years old. The sample was split into males and females as well as into individuals under and over 50 years old. We also divided the sample in 10-year intervals. First, intra- and inter-observer error was estimated in order to assess repeatability and reproducibility of the variables employed for age-at-death estimation. Then, the validity (correct classification performance) of DRNNAGE for each anatomical region individually, as well as all combined, was evaluated on each demographic separately and on the pooled sample. According to the results, some of the variables showed very low repeatability and reproducibility, thus their use should be cautious. The DRNNAGE software showed overall highly accurate age-at-death estimates for individuals older than 50 years, but poor on younger adults, with only exception the cranial sutures, which performed surprisingly well for all age groups. Overall, these results support the importance of cross-validation and the use of population-specific methods in forensic anthropology.

Frequency distribution of HLA class I and II alleles in Greek population and their significance in orchestrating the National Donor Registry Program.

Human leukocyte antigens (HLA) represent one of the most polymorphic systems in humans, responsible for the identification of foreign antigens and the presentation of immune responses. Therefore, HLA is considered to play a major role in human disorders, donor-recipient matching and transplantation outcomes. This study aimed to determine the HLA class I and II alleles and haplotypes in the Greek population. Moreover, a comparative analysis of HLA alleles and haplotype frequencies found in Greek and pooled European populations was also performed to acquire a better knowledge about the HLA alleles distribution. A total number of 1896 healthy individuals were typed for their HLA alleles in the National Tissue Typing Center of Greece. High-resolution HLA typing for the HLA-A, -B, -C and -DR, -DQ, -DP with the use of the next-generation sequencing analysis was performed, followed by data analysis for establishing the HLA allele and haplotype differences. The results of this study showed that the most frequent alleles for the HLA-A were the A*02:01:01 (27.1%), *24:02:01 (14.4%), *01:01:01 (9.3%), for the HLA-B were the B*51:01:01 (15.3%), *18:01:01 (9.7%), *35:01:01 (6.8%) and for the HLA-C were the C*04:01:01 (15.4%), *07:01:01 (13.1%), *12:03:01 (9.6%). For the HLA class II, the most frequent alleles for the HLA-DRB1 were the DRB1*11:04:01 (16.4%), *16:01:01 (11.3%), *11:01:01 (9.5%), for the HLA-DQB1 were the DQB1*03:01:01 (30.5%), *05:02:01 (15.1%), *05:01:01 (10.6%) and for the HLA-DPB1 were the DPB1*04:01:01 (34.8%), *02:01:01 (11.6%), *04:02:01 (7.3%). Additionally, the most frequent haplotypes were the A*02:01:01∼C*07:01:01-B*18:01:01∼DRB1*11:04:01 (2.3%), followed by the A*01:01:01∼C*07:01:01∼B*08:01:01∼DRB1*03:01:01 (2.2%), A*24:02:01∼C*04:01:01∼B*35:02:01∼DRB1*11:04:01 (1.4%) and A*02:01:01∼C*04:01:01∼B*35:01:01-DRB1*14:01:01 (1.2%). The results herein were comparable to those obtained from the pooled European populations. Moreover, these results can be used for the improvement of the donor-recipient matching procedure and to understand better the disease association in Greece.

Subjective health literacy skills among Greek secondary school students: results from a national-wide survey.

Health literacy is a significant element of education and is inextricably linked to children's and adolescents' growth and prosperity. It is critical to monitor students' health literacy on a nationwide scale and identify the factors that influence it in order to create policies that advance it. The purpose of this study was to determine the health literacy level of Greek secondary school students and to correlate it with possible determinants such as personal and family characteristics, social support and personal and/or family illness experiences. A representative sample of 2749 seventh-, ninth-, and tenth-grade students was involved. Results showed that a higher motivation to learn about health topics and having positive social interactions and support were strongly associated with a higher level of health literacy. Gender, high academic achievement, absence of learning disabilities, gender, preference for biology and informatics and primary source of health information were also found to influence the skills' level. In order to enhance health literacy, the Greek educational system should take measures to include health literacy skills development goals in their curricula.

The management of deep carious lesions and the exposed pulp in fully developed and immature teeth with irreversible pulpitis: a questionnaire-based study among Greek dentists.

OBJECTIVES: The study aimed to identify the preferred management techniques used by dentists in Greece for treating deep carious lesions or pulp exposure during the removal of carious tissue in teeth with irreversible pulpitis. Additionally, the study sought to explore how patient-related factors (such as age and symptoms) and operator-related factors (like material choice and the use of antibiotics) influence these management decisions. MATERIALS AND METHODS: The questionnaire, developed by five investigators, was divided into two parts: the first gathered respondent demographics, and the second presented clinical scenarios of deep carious lesions, requesting treatment strategies, materials used, and antibiotic prescription practices. The scenarios described patients with intense spontaneous pain and very deep carious lesions, differentiated by age and tooth development status.Data collection was via Google Drive, with analysis performed using SPSS 28, Chi-square, and Fisher's exact tests, with significance set at p < 0.05. RESULTS: The study polled 453 Greek dentists about their treatment choices, for deep carious lesions in mature and immature teeth with irreversible pulpitis The majority favored root canal treatment for mature teeth, however quite a few opted for partial or cervical pulpotomy. MTA emerged as the preferred capping material, emphasizing its biocompatibility. Hemostasis management varied, with saline and sodium hypochlorite as popular choices. In cases of immature teeth, a shift towards vital pulp therapy was evident, reflecting a preference for preserving healthy pulp to avoid complex procedures. CONCLUSIONS: Challenges identified include varying treatment preferences, the significance of bleeding control in vital pulp therapy, and the limited use of antibiotics for irreversible pulpitis. While the study has limitations, including sample size and potential biases, its findings offer valuable insights into the decision-making processes of Greek dentists. CLINICAL RELEVANCE: Future research and ongoing education within the dental community could contribute to standardizing treatment approaches and optimizing outcomes for patients with deep carious lesions and irreversible pulpitis.

[Medical practice in classical Greece : The neurological and psychiatric case reports of the Hippocratic Corpus]. / Medizinische Praxis im klassischen Griechenland : Die neurologischen und psychiatrischen Fallberichte des Corpus Hippocraticum.

OBJECTIVE: Which theoretical and practical competences do the neurological and psychiatric case histories of the Hippocratic Corpus convey? MATERIAL AND METHODS: The 431 Hippocratic case histories have been studied for reports and communication on the diagnostics, treatment and prognosis of single persons and groups of patients suffering from neurological and psychiatric diseases. RESULTS: In the 7 books of the Hippocratic Epidemics, a total of 128 patients with neurological and psychiatric symptoms are described. Epidemic fever and its variants were the leading predisposing conditions and the main symptoms were delirium, coma, insomnia, headache, speech disorders and convulsions. A number of patients with phrenitis and opisthotonos are also reported. The majority of the sick persons were male, were teenagers or adults and 47 of them are mentioned by name. The patient's information about the course is often just as informative as the doctor's observations. Treatment was limited to physical and dietary measures. DISCUSSION: The Hippocratic physician diagnosed and attempted to treat a large number of neurological and psychiatric diseases. The often almost continuous observations of the patients led to astonishingly precise predictions of the course and the prospects of recovery. Numerous symptoms described in the case studies, including carphologia and opisthotonus, have entered the neurological vocabulary. The retrospective etiological analysis of the reports leads to the almost explicit identification of neurosyphilis and encephalitis lethargica. The therapeutic measures described by the author were, as the changeable course of the diseases shows, only of limited effectiveness despite a very differentiated application over time, both against the underlying diseases and the neurological and psychiatric complications.

Validation and assessment of psychometric properties of the Greek Eating Behaviors Assessment for Obesity (GR-EBA-O).

INTRODUCTION: With increasing morbidity and risk of death, obesity has become a serious health problem largely attributable to difficulties in finding proper treatments for related diseases. Many studies show how detecting abnormal eating behaviors could be useful in developing effective clinical treatments. This study aims at validating the Greek version of the Eating Behaviors Assessment for Obesity (EBA-O). METHOD: After a double English/Greek forward/backward translation of the EBA-O, 294 participants completed the Greek version (GR-EBA-O), the Eating Disorder Examination Questionnaire, the Binge Eating Scale, and the Yale Food Addiction Scale. Confirmatory factor analysis (CFA) and construct validity were calculated, and Two-way MANOVA was computed with the factors of GR-EBA-O controlling for sex and BMI categories. RESULTS: CFA confirmed the second-order five factors (i.e., food addiction, night eating, binge eating, sweet eating, and prandial hyperphagia) structure of the original EBA-O with excellent fit indices. GR-EBA-O factors were highly correlated. The GR-EBA-O subscales were also significantly correlated with the remaining measures, demonstrating good concurrent validity. CONCLUSION: The Greek version of the EBA-O has demonstrated sound psychometric properties and appears a reliable and user-friendly tool to identify pathological eating behaviors in obesity. LEVEL OF EVIDENCE: V, descriptive research.

The Processing of Lexical Ambiguity: Evidence from Child and Adult Greek.

The aim of the study is to examine the effect of sentential context on lexical ambiguity resolution in Greek adults and typically developing children. Context and word frequency are factors that can affect lexical processing, however, the role of them has not been thoroughly examined in Greek. To this aim, we assessed sentence context effects in homonym meaning activation in monolingual speakers of Greek, children and adults, using a cross-modal priming paradigm. Additionally, all participants conducted a verbal working memory task and an inhibition task so as to examine whether the use of sentential context for lexical ambiguity resolution relates to age and/or cognitive processing capacity. The data analysis showed (a) major processing differences between adults and children due to ambiguity and sentential context, (b) children's processing times affected by cognitive skills while adults' processing unaffected, and (c) visual word recognition intact for all participants.

Discrimination of Second Language Vowel Contrasts and the Role of Phonological Short-Term Memory and Nonverbal Intelligence.

Although extensive research has focused on the perceptual abilities of second language (L2) learners, a significant gap persists in understanding how cognitive functions like phonological short-term memory (PSTM) and nonverbal intelligence (IQ) impact L2 speech perception. This study sets out to investigate the discrimination of L2 English monophthongal vowel contrasts and to assess the effect of PSTM and nonverbal IQ on L2 speech perception. The participants consisted of adult monolingually-raised Greek speakers, who completed an AX discrimination test, a digit span test, and a nonverbal intelligence test. A control group of English speakers also completed the AX test. Data were analyzed using Bayesian regression models. The results revealed that Greek speakers exhibited below chance discrimination for the majority of L2 vowel contrasts, consistently underperforming in comparison to the control group. Intriguingly, the study did not provide substantial evidence in favor of more accurate discrimination of L2 contrasts by Greek participants with high PSTM compared to those with low PSTM. However, the study yielded compelling evidence indicating that Greek participants with higher IQ demonstrated superior accuracy in discriminating most L2 contrasts compared to their lower IQ counterparts. The limited influence of PSTM on speech perception suggests the need for further exploration, considering the potential impact of test methodologies and the intricate interplay of other confounding factors. Furthermore, the study uncovers a noteworthy relationship between nonverbal IQ and L2 speech perception, likely linked with the association of high IQ with enhanced attentional capacities, information processing abilities, and learning skills-all of which are pivotal for accurate speech perception.

Do Oral and Silent Word-Reading Fluency Rely on the Same Cognitive-Linguistic Skills? Evidence from a Cross-Sectional Study in Greek.

Researchers tend to use oral- and silent-reading fluency measures interchangeably and to generalize research findings across reading modes, especially from oral to silent reading. In this study, we sought to examine if oral and silent word-reading fluency rely on the same cognitive-linguistic skills. Three hundred and forty-five Greek children (80 from Grade 2, 85 from Grade 4, 91 from Grade 6, and 89 from Grade 10) were assessed on measures of general cognitive ability, speed of processing, phonological awareness, rapid automatized naming, orthographic knowledge, articulation rate, and word-reading fluency (oral and silent). Results of hierarchical regression analyses revealed that phonological awareness was a unique predictor of both reading outcomes in Grade 2 and orthographic knowledge was a unique predictor of both reading outcomes in Grades 4, 6, and 10. However, rapid automatized naming predicted only oral word-reading fluency. These findings suggest that silent and oral word-reading fluency do not necessarily rely on the same cognitive-linguistic skills at the same grade level and we need to exercise some caution when we generalize the findings across reading modes.

Temporal, spectral and amplitude characteristics of the Greek fricative /s/ in hearing-impaired and normal-hearing speech.

Fricatives, and especially sibilants, are very frequently misarticulated by speakers with hearing loss. Misarticulations can result in phonemic contrast weakening or loss, compromising intelligibility. The present study focuses on the examination of acoustic characteristics of the Greek alveolar fricative /s/, an articulatorily demanding sound, produced by young adult speakers with profound hearing impairment and with normal hearing. An array of variables was examined using mixed-effects and random forest models aiming to assess the effectiveness of various measures in differentiating hearing-impaired and normal-hearing /s/ production. Significant differences were found in spectral and amplitude measures, but not in temporal measures. In hearing-impaired speech, spectral slope and RMS amplitude had significantly lower values, indicating a more distributed spectrum, suggestive of decreased flow velocity through the fricative constriction. Also, a trend for concentration of energy at lower frequencies was observed suggesting more posterior fricative articulation than normal. Moreover, measures capturing the variation of frequency and amplitude over time revealed different patterns of sibilance development across time than normal, denoting the production of a less well-formed or less sibilant /s/ by speakers with hearing impairment. The investigation of contextual effects on /s/ in hearing-impaired speech showed increased spectral variance, negative skewness and lower kurtosis in the labial (rounded) context /u/ in relation to the nonlabial contexts /i/ and /a/, indicating a more diffuse, less compact spectrum with concentration at high frequencies. Findings are discussed in relation to previous literature on fricative production by speakers with hearing impairment and normal hearing in Greek and other languages.

Phonological assessment for Greek (PAel) test: Reliability and validity in 4-to 6-year-old preschool children.

Single-word phonological tests are widely used for detecting children at risk for Speech Sound Disorders (SSDs). However, specific conceptual and operational criteria should be evaluated to ensure that these assessments are valid and reliable and can serve as diagnostic tools. The current study aimed to investigate the validity and reliability of the screener of a phonological Greek instrument, named the Phonological Assessment for Greek (PAel) comparing the phonological performance of typically developing (TD) children and children with SSDs, aged 4 to 6 years. The participants were 20 TD children and 40 children with SSDs. All participants completed the screener of PAel, the 70-word list of the standardised Test of Phonetic and Phonological Development (TPPD), and a language test, namely the Action Picture Test. Participants who scored below the 25th percentile on the language test were excluded. Phonological analysis revealed that PAel has high content validity. The participants who had received a diagnosis of SSDs presented restricted consonant and cluster inventories and significantly lower whole-word match levels in comparison to their TD peers. The overall Spearman's correlation coefficients between PAel and TPPD were 0.611 for TD children (p < 0.001) and 0.875 for children with SSDs (p < 0.001), indicating good criterion validity. The tool demonstrated strong test-retest reliability and inter-rater reliability with Spearman values exceeding 0.85, and Intra-class correlation coefficients over 0.90. Overall, the results suggest that PAel has satisfactory reliability and validity and can be used as an assessment tool to detect children at risk for SSDs.

Preface to the special issue "Typical and atypical speech development in Greek".

This special issue of Clinical Linguistics and Phonetics presents a selection of papers, four in total, from the first thematic workshop entitled "Phonetic/phonological aspects of typical and atypical speech development with emphasis on Greek" which took place during the 25th International Symposium on Theoretical and Applied Linguistics held at Aristotle University in Thessaloniki in May 2022. It also includes one additional contribution within the thematic scope of the volume that was submitted to the journal independently of the workshop. Papers examine data from different clinical populations, including a clinical case study, as well as data or theoretical background from typical groups. They address aspects of speech production in childhood, adolescence and early adulthood. They thus reflect the aim of the workshop which was to provide a forum to researchers for the exchange of findings covering different populations (typical and clinical), age groups, genders, and various aspects of production. The ultimate goal was the formation of a working group that would bring together researchers with a special interest in phonetics and phonology, explore factors that influence speech acquisition and development in typical and atypical populations, convene and discuss present and future directions in speech acquisition and development with emphasis on the Greek language.

Child speech developmental norms in Greek monolinguals: whole word and consonant accuracy.

Child phonological development in standard Greek is aptly represented by both single-case and cross-sectional studies. While some quantitative measures exist, such as the 75% criterion in the acquisition of singletons and clusters, reported norms require replication to fine-tune existing indicators, inform non-existent ones, and better reflect children's typical developmental speech in contemporary Greece. Our cross-sectional study addresses this gap, in terms of consonant inventory acquisition, and percentage accuracy of words, singletons, clusters, and cluster reductions. Phonological Assessment for Greek (PAel) procedures facilitated data elicitation from 254 Greek-speaking participants, aged 2;0-7;0, equally represented for gender. Our study comprehensively informs quantitative norms on whole word accuracy (WWA), percentage of consonants correct (PCC), PCC variation across the different age groups of children, and the WWA-PCC correlation along the developmental path in this cross-sectional study. A schematic representation models children's normative PCC-WWA profiles, facilitating the determination of phonological disorder in Greek with direct clinical application on diagnosis and intervention.

Conspiring simplification strategies of [Obstruent+Liquid] clusters in a case study of child Greek: emergence of the marked.

This paper addresses the idiosyncratic cluster simplification patterns observed in a child with disordered phonological development, who is acquiring Greek. The child has mastered word-internal and word-final codas and clusters of reversed sonority. However, the child does not realise the target well-formed tautosyllabic [Obstruent+Liquid] clusters with rising sonority. The child's system requires a single onset with maximum sonority dispersion between the onset and the syllable nucleus. As a result, cluster simplification occurs, via reduction to the less sonorous Obstruent - the most prevalent reduction pattern cross-linguistically. However, at the same time, the grammar requires faithful realisation of the target segment number. This requirement is fulfiled through two distinct conspiring metathesis patterns, distributed complementarily, resulting in the realisation of marked structures. The patterns depend on the position of the cluster within the target word. In word internal position, a compensatory metathesis of the Liquid takes place in the preceding syllable coda. In word initial position, the Manner of Articulation of the metathesised Liquid is delinked, while its Coronal Place of Articulation is faithfully preserved, and is realised by default as a Coronal Sibilant [s]. The latter Sibilant is attached as an appendix to the syllable node at the word left-edge. We argue that, in the grammar of this child, there is a-synchronisation between the development of the prosodic word layer and the development of syllable layer. Specifically, a-synchronisation is evident in the development of the (branching) onset syllabic subconstituent.

Assessing the Impact of Bilingualism on the Linguistic Skills of Children with Autism Spectrum Disorder (ASD) in Greece: A Scoping Review.

(1) Background and Objectives: This review aims to identify the latest literature on the possible effect of bilingualism on the linguistic skills of children with autism spectrum disorder (ASD) residing in Greece. (2) Materials and Methods: The literature was searched in the databases of Scopus and PubMed by selecting articles and by reviewing four studies published in peer-reviewed journals. This Scoping Review is based on the standards of PRISMA recommendations for scoping reviews, while the PCC framework was used as a guide to construct clear and meaningful objectives and eligibility criteria. (3) Results: The publications included in the review addressed a variety of language-related skills, including morphology, the syntax-pragmatics interface, narrative ability, as well as both receptive and expressive language skills. (4) Conclusions: Three out of four studies provide evidence that bilingual ASD children are not disadvantaged compared to monolingual peers but rather enjoy some benefits, to a certain extent, due to bilingualism. However, the number of the reviewed studies as well as the limitations of the studies themselves render this conclusion tentative. Additionally, the findings set guidelines that speech therapists, educators, psychologists, and doctors in the Greek context need to follow when treating or educating bilingual children with ASD.

Deep Learning-based structure modelling illuminates structure and function in uncharted regions of ß-solenoid fold space.

Repeat proteins are common in all domains of life and exhibit a wide range of functions. One class of repeat protein contains solenoid folds where the repeating unit consists of ß-strands separated by tight turns. ß-solenoids have distinguishing structural features such as handedness, twist, oligomerisation state, coil shape and size which give rise to their diversity. Characterised ß-solenoid repeat proteins are known to form regions in bacterial and viral virulence factors, antifreeze proteins and functional amyloids. For many of these proteins, the experimental structure has not been solved, as they are difficult to crystallise or model. Here we use various deep learning-based structure-modelling methods to discover novel predicted ß-solenoids, perform structural database searches to mine further structural neighbours and relate their predicted structure to possible functions. We find both eukaryotic and prokaryotic adhesins, confirming a known functional linkage between adhesin function and the ß-solenoid fold. We further identify exceptionally long, flat ß-solenoid folds as possible structures of mucin tandem repeat regions and unprecedentedly small ß-solenoid structures. Additionally, we characterise a novel ß-solenoid coil shape, the FapC Greek key ß-solenoid as well as plausible complexes between it and other proteins involved in Pseudomonas functional amyloid fibres.

Transcriptional repression in stochastic gene expression, patterning, and cell fate specification.

Development is often driven by signaling and lineage-specific cues, yielding highly uniform and reproducible outcomes. Development also involves mechanisms that generate noise in gene expression and random patterns across tissues. Cells sometimes randomly choose between two or more cell fates in a mechanism called stochastic cell fate specification. This process diversifies cell types in otherwise homogenous tissues. Stochastic mechanisms have been extensively studied in prokaryotes where noisy gene activation plays a pivotal role in controlling cell fates. In eukaryotes, transcriptional repression stochastically limits gene expression to generate random patterns and specify cell fates. Here, we review our current understanding of repressive mechanisms that produce random patterns of gene expression and cell fates in flies, plants, mice, and humans.

Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.

BACKGROUND: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource. RESULTS: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue. CONCLUSIONS: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis.