Analysis Of Genetic Data Research Articles

Neuron Navigator 1 (Nav1) regulates the response to cocaine in mice

Genetic variation accounts for much of the risk for developing a substance use disorder, but the underlying genetic factors and their genetic effector mechanisms are mostly unknown. Inbred mouse strains exhibit substantial and heritable differences in the extent of voluntary cocaine self-administration. Computational genetic analysis of cocaine self-administration data obtained from twenty-one inbred strains identified Nav1, a member of the neuron navigator family that regulates dendrite formation and axonal guidance, as a candidate gene. To test this genetic hypothesis, we generated and characterized Nav1 knockout mice. Consistent with the genetic prediction, Nav1 knockout mice exhibited increased voluntary cocaine intake and had increased motivation for cocaine consumption. Immunohistochemistry, electrophysiology, and transcriptomic studies were performed as a starting point for investigating the mechanism for the Nav1 knockout effect. Nav1 knockout mice had a reduced inhibitory synapse density in their cortex, increased excitatory synaptic transmission in their cortex and hippocampus, and increased excitatory neurons in a deep cortical layer. Collectively, our results indicate that Nav1 regulates the response to cocaine, and we identified Nav1 knockout induced changes in the excitatory and inhibitory synaptic balance in the cortex and hippocampus that could contribute to this effect.

How to cross the desert if you are small and need mountains? Out‐of‐Ethiopia dispersal in Afromontane shrews

AbstractAimThe Eastern Afromontane Biodiversity Hotspot (EABH) offers an ideal location to investigate the evolutionary mechanisms producing a high level of endemic biodiversity. We tested the hypothesis that the cradle of Eastern Afromontane diversity is in the largest sub‐region of the EABH montane archipelago, that is the Ethiopian Highlands. Further, we expected that climate oscillations followed by elevational shifts in montane habitats facilitated the dispersal of small mammal populations across unsuitable arid lowlands.LocationMountains and highlands of East Africa.TaxonShrews of the genus Crocidura (Eastern Afromontane phylogenetic clade).MethodsWe collected comprehensive genetic data from 511 (mitochondrial gene for cytochrome b) and 147 (double digest Restriction‐Associated DNA sequencing) samples of Crocidura shrews across the EABH. We estimated phylogenetic relationships with Bayesian and Maximum Likelihood approaches. Population genetic analyses were performed in STRUCTURE to evaluate the internal structure of species outside Ethiopia. Ancestral area and dispersal routes were analysed by the BioGeoBears package.ResultsSix major phylogenomic clades were delimited based on concatenated nuclear loci. The mitochondrial phylogeny roughly matches nuclear phylogenies, but with poorer resolution. Five of the six revealed clades are restricted to the Ethiopian Highlands, which is unambiguously the cradle of the diversity of this group of mammals (also confirmed by the biogeographic analysis). All non‐Ethiopian and a single Ethiopian species fall into the sixth clade with poorly resolved internal relationships. Detailed population genetic analysis of SNP data revealed a pronounced structure with multiple gene pools in this clade; however, this structure only partly corresponds with the current taxonomy.Main ConclusionsEastern Afromontane Crocidura shrews originated in the Ethiopian Highlands. They radiated there, and through a single southward dispersal event across the Turkana depression, they colonised the rest of the EABH in response to diverse geomorphology and climatic changes during the Plio‐Pleistocene.

Genetic data to describe the hybrid zone between Bufo bufo (Linnaeus, 1758) and Bufo verrucosissimus (Pallas, 1814) in northeastern Türkiye

Abstract Hybrid zones are geographic areas where individuals from distinct taxa meet, mate, and hybridize. These zones may have complex histories, but many of them originated relatively recently, during climatic oscillations in the Quaternary, following range shifts of formerly isolated, well-differentiated lineages. The Bufo bufo species group comprises four species distributed over the Western Palearctic. Whereas the contact zone between Bufo bufo and B. spinosus in western Europe has been well characterized, little is known about other species contacts. Here we focused on the contact between B. verrucosissimus and B. bufo in northeastern Türkiye, using mtDNA and microsatellite markers to describe genetic structure and patterns of admixture in the hybrid zone based on Bayesian clustering and cline analyses. Both species meet in a narrow contact zone at Rize province, with restricted introgression suggesting barriers to hybridization consistent with species status. Spatial population genetic analyses of microsatellite data pinpoint a possible enclave population of B. bufo at the Borçka district in Artvin province, isolated within the B. verrucosissimus range. The centers of the microsatellite and mtDNA-based clines are slightly displaced, with B. verrucosissimus mtDNA introgressing about 33 km W of the nuclear contact. Hybrid zone dynamics seem to be associated with range shifts mediated by Pleistocene glacial cycles and/or sex-biased dispersal.

Evaluating alternative models of youth externalizing using quantitative genetic analyses.

Interest has increased in the recent literature on characterizing psychopathology dimensionally in hierarchical models. One dimension of psychopathology that has received considerable attention is externalizing. Although extensively studied and well-characterized in late adolescents and adults, delineation of the externalizing spectrum in youth has lagged behind. As a complement to structural analyses of externalizing, in this study, we use quantitative genetic analyses of twin data to adjudicate among alternative models of youth externalizing that differ in granularity. Specifically, we compared model fit, estimates of genetic and environmental influences on the externalizing dimension, and the average, variability, and precision of genetic and environmental influences on individual symptoms due to the externalizing dimension, specific symptom dimensions, and unique etiological influences. Given that none of these criteria are definitive on their own, we looked to the confluence of these criteria to exclude particular models while highlighting others as leading contenders. We analyzed parent-report data on 38 externalizing symptoms from a population-representative, ethnically diverse sample of 883 youth twin pairs (51% female), who were on average 8.5 years old. Although models including an externalizing composite and attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder diagnoses and symptom dimensions showed similar heritability to latent variable models of externalizing, models that included latent dimensions of externalizing and more fine-grained symptom dimensions fit better and were more balanced in the magnitude of genetic and environmental influences on individual symptoms due to the externalizing dimension and specific symptom dimensions. Pending replication, these more granular and elaborated model(s) can be useful for advancing research on causes and outcomes of youth externalizing and its fine-grained specific components. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Features and Prospects of the Use of X-chromosomal Tandem Repeats in Forensic Molecular Genetic Examination

When conducting molecular genetic examinations, biological specialists in Ukraine usually use kits for autosomal STR repeats and Y-chromosome repeats and do not use kits for X-chromosomal STR repeats at all. The research paper’s purpose is to analyze the literature data to determine the characteristics of the X chromosome, the possibilities of using X chromosome typing kits, and their implementation in the forensic practice of experts in molecular genetic examinations. The criteria for searching and STR loci are defined, the characteristics of commercial kits (in particular, Argus X-8 PCR Amplification Kit from Biotype AG and Investigator Argus X-12 QS Kit (Germany), X19 X-STRs amplification kit from AGCU ScienTech Inc. and 19X Direct ID system (China)) the directions of their use are considered. The data of scientific and methodological literature on the frequency of mutations, the prevalence of alleles in populations, and the prospects for creating a common database of X-STR repeats are studied. To achieve this goal, general and special methods were used, among which the main one is the structural genetic analysis and synthesis of X-chromosome research data from the standpoint of forensic genetics. The methods of formalizing the characteristics of commercial X-STR repeat kits and their comparative analysis, systematizing possible areas of STR repeat use taking into account the peculiarities of X chromosome inheritance, and generalizing population studies conducted in European countries were also used.

Phylogenetic history of golden moles and tenrecs (Mammalia: Afrotheria)

Abstract We conducted a phylogenetic analysis of genetic and anatomical data focusing on golden moles (Chrysochloridae) and tenrecs (Tenrecidae). Our results support the now well-resolved topology for extant tenrecids, in addition to the paraphyly of ‘Chrysochlorinae’ and the genera Chrysochloris and Chlorotalpa as traditionally used. Carpitalpa arendsi is the sister taxon to Neamblysomus; together, they compose the sister clade of Amblysomus. Unexpectedly, Calcochloris obtusirostris is the sister taxon of Chrysospalax. The oldest divergence within crown Chrysochloridae is likely to be the node separating Eremitalpa–Huetia or Eremitalpa alone from the remaining species. A Chrysochloris–Cryptochloris root appears most frequently under equally weighted parsimony or with few or no sampled tenrecids, suggesting that it is artefactual. The tropical genus Huetia is among the most widely distributed and anatomically polymorphic in our sample. Eremitalpa and Huetia have a relatively unspecialized hyoid apparatus and short angular process of the dentary. These elements in Huetia show a particular resemblance to those of the Namibian fossil Namachloris, which we reconstruct as a stem chrysochlorid. Crown chrysochlorids are geologically younger than crown tenrecids and probably diversified in the Miocene around the same time as the tenrecid genus Microgale. Fossils of both groups from Eocliff in Namibia are probably late Eocene to early Miocene in age.

The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data

BackgroundX-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient’s lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry.ResultsThe International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately − 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH.ConclusionThe data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.

Applications for Deep Learning in Epilepsy Genetic Research.

Epilepsy is a group of brain disorders characterised by an enduring predisposition to generate unprovoked seizures. Fuelled by advances in sequencing technologies and computational approaches, more than 900 genes have now been implicated in epilepsy. The development and optimisation of tools and methods for analysing the vast quantity of genomic data is a rapidly evolving area of research. Deep learning (DL) is a subset of machine learning (ML) that brings opportunity for novel investigative strategies that can be harnessed to gain new insights into the genomic risk of people with epilepsy. DL is being harnessed to address limitations in accuracy of long-read sequencing technologies, which improve on short-read methods. Tools that predict the functional consequence of genetic variation can represent breaking ground in addressing critical knowledge gaps, while methods that integrate independent but complimentary data enhance the predictive power of genetic data. We provide an overview of these DL tools and discuss how they may be applied to the analysis of genetic data for epilepsy research.

Clinical presentation and genetic variants in patients with autoinflammatory diseases: results from the German GARROD registry

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.

Taxonomic inflation and a reconsideration of speciation in the Andes: the case of the high-elevation tree frog Dendropsophus molitor (Anura: Hylidae)

Abstract Dendropsophus molitor is a hylid frog endemic to the Eastern Cordillera of the Colombian Andes, where it exhibits extensive geographic variation in size and colour pattern. Previous multivariate analyses of acoustic and genetic data suggested that northern and southern populations of D. molitor were distinct lineages, and consequently, the northern populations were described as Dendropsophus luddeckei. In this study, we conducted morphometric and genetic analyses of populations of D. molitor and D. luddeckei to test the validity of this recent taxonomic split. We sequenced the mitochondrial genes 12S, 16S, and COI, and the nuclear marker POMC, and also tested whether variation in the MC1R gene was associated with colour polymorphism in these frogs. Phylogenetic analyses recovered D. molitor and D. luddeckei as polyphyletic and species delimitation tests failed to recover them as separate lineages. Genetic differentiation between populations was mostly explained by high intra- and interpopulation variation in the absence of a north-south split, and we found no differences in morphometry between northern and southern populations. In addition, the coding region of MC1R is not associated with colour polymorphism. Thus, multiple lines of evidence suggest that D. luddeckei is not a valid species and D. molitor should be considered a single species. Our study highlights the danger of taxonomic inflation in the face of limited geographic sampling and a lack of clear diagnostic characters.

Genetic Variants Identified by Whole Exome Sequencing in a Large Italian Family with High Plasma Levels of Factor VIII and Von Willebrand Factor.

High plasma levels of factor VIII (FVIII) and von Willebrand factor (VWF) have been indicated as independent risk factors for venous thromboembolism. However, the genetic factors responsible for their increase remain poorly known. In a large Italian family with high FVIII/VWF levels and thrombotic episodes, whole exome sequencing (WES) was performed on 12 family members to identify variants/genes involved in FVIII/VWF increase. Twenty variants spread over a 8300 Kb region on chromosome 5 were identified in 12 genes, including the low frequency rs13158382, located upstream of the MIR143/145 genes, which might affect miR-143/145 transcription or processing. The expression of miR-143/145 and VWF mRNA were evaluated in the peripheral blood mononuclear cells of six family members. Members with the variant (n = 3) showed lower levels of both miRNAs and higher levels of VWF mRNA compared to members without the variant (n = 3). An analysis of genetic and expression data from a larger cohort of individuals from the 1000 Genomes and GEUVADIS project confirmed a statistically significant reduction (p-value = 0.023) in miR-143 in heterozygous (n = 35) compared to homozygous wild-type individuals (n = 386). This family-based study identified a new genetic variant potentially involved in VWF increase by affecting miR-143/145 expression.

Genetic evidence supporting a causal role of Janus kinase 2 in prostate cancer: a Mendelian randomization study

Background Janus kinase-2 (JAK2) inhibitors are now being tried in basic research and clinical practice in prostate cancer (PCa). However, the causal relationship between JAK2 and PCa has not been uniformly described. Here, we examined the cause-effect relation between JAK2 and PCa. Methods Two-sample Mendelian randomization (MR) analysis of genetic variation data of JAK2, PCa from IEU OpenGWAS Project was performed by inverse variance weighted, MR-Egger, and weighted median. Cochran’s Q heterogeneity test and MR-Egger multiplicity analysis were performed to normalize the MR analysis results to reduce the effect of bias on the results. Results Five instrumental variables were identified for further MR analysis. Specifically, combining the inverse variance-weighted (OR: 1.0009, 95% CI: 1.0001–1.0015, p = 0.02) and weighted median (OR: 1.0009, 95% CI: 1.0000–1.0017, p = 0.03). Sensitivity analysis showed that there was no heterogeneity (p = 0.448) and horizontal multiplicity (p = 0.770) among the instrumental variables. Conclusions We found JAK2 was associated with the development of PCa and was a risk factor for PCa, which might be instructive for the use of JAK2 inhibitors in PCa patients.

Population genetic structure of intensively exploited pikeperch (Sander lucioperca) in Lake Balaton (Hungary)

Pikeperch (Sander lucioperca Linnaeus, 1758) is a wide-ranged percid predator fish characterised by a great ecological value in the Eurasian freshwater and brackish ecosystems. It is also one of the most famous fish species of Lake Balaton (Hungary), where a unique (genetically separated) pikeperch stock lives. However, until now, no detailed information was available about the pikeperch population genetic structure in Lake Balaton. In the present study, the population genetic structure of the pikeperch assemblages in the lake was revealed by using microsatellite markers. Commercial fishery and angler catch data going back more than 100 years verified that the pikeperch has always been a key element of Lake Balaton’s fish stock utilization. Results of genetic data analyses showed that the pikeperch in the Lake Balaton forms a metapopulation system, in which only the westward stocks show certain separation. Moreover, it seems that the exploitation and mass fish kills that happened in the 1960s and 1970s may have had only a slight impact on the population genetic structure of Balaton pikeperch stocks. The information about genetic features and utilization changes of pikeperch stocks can help to develop area-specific management plans and ensure the long-term survival of this carnivore fish species characteristic of Lake Balaton.

A novel smoothed (SMO) point mutation in congenital tibial hemimelia: a case report

BackgroundCongenital tibial hemimelia (CTH [MIM: 275220]) is a rare congenital limb deficiency that manifests as a shortened, curved, dysplastic or absent tibia with polydactyly. In previous studies, mutations of a distant sonic hedgehog (SHH) cis-regulator (ZRS) and a Shh repressor (GLI3) were identified.Case presentationHere, we admitted a 20-month-old boy who manifested with right tibial deformity, varus foot, ankle dislocation, and ipsilateral preaxial polydactyly. After genetic sequencing and data analysis, the results revealed a 443 A > G mutation in the father and a 536 C > T mutation in the mother in exon 2 of the Smoothed (SMO) gene at 7q32.1, with the coexistence of both mutant alleles in the proband/patient.ConclusionsOur report suggests that even though not previously reported, SMO mutations may be associated with limb anomalies such as tibial hemimelia via Hh signaling in humans and has implications for genetic counseling.

Characterization of Microsatellite Markers in Crossbred Ducks

Background: Chicken represents a valuable genetic resource and protein source, it remains a potential threat to human health as they serve as a reservoir for diseases and food borne pathogens. Diversification of the poultry production is one of the viable options to enhance the food production with less susceptibility to the threats from the emerging diseases and changing climatic conditions. Ducks are promising species suitable for the diversification and will be complimentary with an adaption potential from small to commercial farming. Majority of ducks in the country are desi type with a meagre proportion of improved duck strains. genetic characterization by developing duck specific microsatellite markers and designing suitable improvement program are required to be undertaken at the earliest. The microsatellite markers are extensively used for assessing genetic structure, diversity, and relationships. Information about genetic diversity of indigenous duck breeds is important to design effective improvement and conservation strategies. Therefore, the current studies aim at genetic characterization and evaluation of growth, production and reproduction traits of the crosses of local duck population besides undertaking a suitable duck improvement program. Methods: Spectrophotometric evaluation of DNA extraction, Electrophoretic evaluation of DNA extraction , microsatellite primers- Presently, a panel of 10 informative duck microsatellite markers were identified from database as reported by Alyethodi and Kumar (2010) and Huang et al., (2006) and used for the studies, Polymerase chain reaction (PCR) , Documentation of PCR products by Agarose Gel Electrophoresis, Metaphor agarose gel electrophoresis(MAGE)of microsatellites alleles, Determination of molecular size of microsatellite alleles and genotypes, Statistical analysis of population genetics data, Data on genotype of all experimental birds at ten microsatellites were compiled and analyzed using POPGENE® 3.1 software (Yeh et al., 1999) for their population genetics parameters. Results: The study was conducted at College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam, India. In this study, the genomic DNA was isolated and characterized microsatellite loci in crossbred duck (Pati x White Pekin). Ten microsatellites were used to detect polymorphisms in 50 cross bred ducks. A total of 28 nos of alleles were observed and all loci were polymorphic. The number of alleles ranged from 2 to 5 with an average of 2.6 ±0.08 per microsatellite locus. The observed and expected heterozygosity of these polymorphic makers ranged from 0.00 to 0.42 with an average number of 0.047 and 0.41 to 0.82 with an average number of 0.57, respectively. The Polymorphic markers consist of observed heterozygosities of loci were less than 0.50. The polymorphism information content (PIC) of 10 loci ranged from 0.32 to 0.78 with an average of 0.477. Microsatellite markers will be useful tool for constructing the genetic linkage map of the duck as well as comparative mapping with the chicken.

The pursuit of genetic gain in agricultural crops through the application of machine-learning to genomic prediction.

Current practice in agriculture applies genomic prediction to assist crop breeding in the analysis of genetic marker data. Genomic selection methods typically use linear mixed models, but using machine-learning may provide further potential for improved selection accuracy, or may provide additional information. Here we describe SelectML, an automated pipeline for testing and comparing the performance of a range of linear mixed model and machine-learning-based genomic selection methods. We demonstrate the use of SelectML on an in silico-generated marker dataset which simulated a randomly-sampled (mixed) and an unevenly-sampled (unbalanced) population, comparing the relative performance of various methods included in SelectML on the two datasets. Although machine-learning based methods performed similarly overall to linear mixed models, they performed worse on the mixed dataset and marginally better on the unbalanced dataset, being more affected than linear mixed models by the imposed sampling bias. SelectML can assist in the training, comparison, and selection of genomic selection models, and is available from https://github.com/darcyabjones/selectml.

Personalized approach in the diagnostics and treatment of symptomatic epilepsy with déjà vu seizures

The phenomenon of déjà vu (DV) is of interest, occurring in 97% of healthy individuals, while DV can be a manifestation of a number of pathologies, such as Charles Bonnet syndrome, depression, schizophrenia, or temporal lobe epilepsy. Most cases of DV type epiphenomena are associated with hippocampal sclerosis, while up to 90% of patients with mesial temporal sclerosis are drug resistant. Despite the success of pharmacotherapy, the frequency of «uncontrolled» epilepsy in industrialized countries that adhere to modern standards of treatment is from 30 to 40%, and this percentage is higher among patients with symptomatic and cryptogenic forms than among patients with idiopathic epilepsy (respectively: 40% and 26%). In turn, when studying the DV phenomenon and choosing a therapy strategy, it is necessary to establish its origin, determine its clinical significance (whether it is initially pathological or not), and the need for treatment. During the analysis of exome data, a search was made for substitutions in genes associated with arteriovenous malformations, both with autosomal dominant and autosomal recessive types of inheritance. The genes KRIT1, RASA1, IL6, FAM58A, GLML, EPHB4, CCM2, and ELMO2 were analyzed especially carefully. The analysis of genetic data is of great importance in the aspect of preventing cerebrovascular accidents, at the same time, in order to obtain reliable and significant results, in addition to time and financial costs, examination of relatives is also required. Meanwhile, this fact does not mean that every patient needs to conduct a genetic study. The paper presents detailed instructions for supplementing anamnestic information, as well as the results of personalized instrumental and laboratory diagnostics, which made it possible to carry out timely correction of therapy and achieve a prolonged positive effect.

Phenotype and genetic analysis of data collected within the first year of NeuroDev

Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev's first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing data identified a pathogenic or likely pathogenic variant in 13 (17%) of the 75 cases from South Africa and 9 (38%) of the 24 cases from Kenya. Data from the trio pilot are publicly available, and the NeuroDev Project will continue to develop resources for the global genetics community.

NgsJulia: population genetic analysis of next-generation DNA sequencing data with Julia language

A sound analysis of DNA sequencing data is important to extract meaningful information and infer quantities of interest. Sequencing and mapping errors coupled with low and variable coverage hamper the identification of genotypes and variants and the estimation of population genetic parameters. Methods and implementations to estimate population genetic parameters from sequencing data available nowadays either are suitable for the analysis of genomes from model organisms only, require moderate sequencing coverage, or are not easily adaptable to specific applications. To address these issues, we introduce ngsJulia, a collection of templates and functions in Julia language to process short-read sequencing data for population genetic analysis. We further describe two implementations, ngsPool and ngsPloidy, for the analysis of pooled sequencing data and polyploid genomes, respectively. Through simulations, we illustrate the performance of estimating various population genetic parameters using these implementations, using both established and novel statistical methods. These results inform on optimal experimental design and demonstrate the applicability of methods in ngsJulia to estimate parameters of interest even from low coverage sequencing data. ngsJulia provide users with a flexible and efficient framework for ad hoc analysis of sequencing data.ngsJulia is available from: https://github.com/mfumagalli/ngsJulia.

Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations

ObjectivesTo compare associations between the Gilbert syndrome genotype in European populations, measured bilirubin concentrations, genetically predicted bilirubin using this genotype, and a wide range of health outcomes in a large...