Comprehensive Genetic Data Research Articles

Genetic causality of lipidomic and immune cell profiles in ischemic stroke.

Ischemic stroke (IS) is a global health issue linked to lipid metabolism and immune cell responses. This study uses Mendelian randomization (MR) to identify genetic risk factors for IS subtypes using comprehensive genetic data from lipidomic and immune cell profiles. We assessed genetic susceptibility to IS across 179 lipids and 731 immune cell phenotypes using instrumental variables (IVs) from recent genome-wide association studies. A two-sample MR approach evaluated correlations, and a two-step MR mediation analysis explored the role of immune cell phenotypes in the lipid-IS pathway. Sensitivity analyses, including MR-Egger and Cochran Q tests, ensured robust results. Genetic IVs for 162 lipids and 614 immune cell phenotypes were identified. Significant genetic causality was found between 35 lipids and large artery stroke (LAS), with 12 as risk factors (sterol esters, phosphatidylcholines, phosphatidylethanolamines) and 23 as protective factors (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols). For small vessel stroke (SVS), 8 as risk factors (sterol esters, phosphatidylcholines), and 2 as protective factors (phosphatidylinositol, sphingomyelin). For cardioembolic stroke (CS), 2 as risk factors, and 4 as protective factors. Mediation analysis revealed that CCR2 on granulocytes, CD11c on CD62L+ myeloid dendritic cells, and FSC-A on granulocytes mediated the lipid-immune cell-LAS pathway, while CD4 on activated CD4 regulatory T cells and CD4 on activated & secreting CD4 regulatory T cells mediated the lipid-immune cell-SVS pathway. This study identifies genetic links between specific lipids and IS subtypes, highlights immune cells' role in IS risk and mediation, suggests new therapeutic targets, and uncovers IS genetic drivers.

Molecular Phylogenetics and Phylogeography of Malaysian Mousedeer (Tragulus kanchil) Based on Mitochondrial DNA Sequences of the D-Loop Region

Two sympatric mousedeer species, Tragulus kanchil and Tragulus napu, inhabit the Malaysian tropical rainforests. Previous studies have established their phylogenetic relationships based on morphological variations; however, comprehensive genetic data have yet to be extensively used to relate the relationships especially from different populations. The main objectives of this study were to determine the phylogenetic relationships, population genetics, and phylogeography of mousedeer species based on DNA sequences of the mitochondrial D-loop region. DNA from 32 mousedeer samples, representing various populations in Malaysia, was sequenced and analyzed using Neighbor-Joining, Maximum Parsimony, and Bayesian Inference approaches. The phylogenetic analyses showed two main clades representing the populations of T. kanchil and T. napu. The results also showed that the T. kanchil populations in Borneo was separated from Peninsular Malaysia taxa in MP and BI phylogenetic tree. However, Borneo population was nested in east population of Peninsular Malaysia in NJ tree. In addition, the T. kanchil population in Peninsular Malaysia further separated into east and west coast populations of Titiwangsa Range. It was supported with finding in population genetic relation that showed relatively low levels among population. This is expected because some of the populations are isolated geographically. The divergence of these populations is likely due to the Titiwangsa Range which acts as a barrier separating the east and west Peninsular Malaysia populations, and the South China Sea separates the populations of Peninsular Malaysia and Borneo. Molecular clock tree reconstruction showed that the separation of T. kanchil and T. napu occurred around 17.11 million years ago (MYAs). Furthermore, the T. kanchil populations from the east and west Peninsular Malaysia showed a branching pattern from those of Borneo of about 11.04 and 9.14 MYAs, respectively. The results of this study increase our understanding of Malaysian mousedeer phylogeny and phylogeography.

Boosting predictive models and augmenting patient data with relevant genomic and pathway information

The recurrence of low-stage lung cancer poses a challenge due to its unpredictable nature and diverse patient responses to treatments. Personalized care and patient outcomes heavily rely on early relapse identification, yet current predictive models, despite their potential, lack comprehensive genetic data. This inadequacy fuels our research focus—integrating specific genetic information, such as pathway scores, into clinical data. Our aim is to refine machine learning models for more precise relapse prediction in early-stage non-small cell lung cancer. To address the scarcity of genetic data, we employ imputation techniques, leveraging publicly available datasets such as The Cancer Genome Atlas (TCGA), integrating pathway scores into our patient cohort from the Cancer Long Survivor Artificial Intelligence Follow-up (CLARIFY) project. Through the integration of imputed pathway scores from the TCGA dataset with clinical data, our approach achieves notable strides in predicting relapse among a held-out test set of 200 patients. By training machine learning models on enriched knowledge graph data, inclusive of triples derived from pathway score imputation, we achieve a promising precision of 82% and specificity of 91%. These outcomes highlight the potential of our models as supplementary tools within tumour, node, and metastasis (TNM) classification systems, offering improved prognostic capabilities for lung cancer patients. In summary, our research underscores the significance of refining machine learning models for relapse prediction in early-stage non-small cell lung cancer. Our approach, centered on imputing pathway scores and integrating them with clinical data, not only enhances predictive performance but also demonstrates the promising role of machine learning in anticipating relapse and ultimately elevating patient outcomes.

The Phylogenetic Relationship of Lamiinae (Coleoptera: Cerambycidae) Using Mitochondrial Genomes.

Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological characteristics are not sufficient to resolve species phylogenetic studies perfectly. At the same time, the full mitochondrial genome contains more comprehensive genetic data. Benefiting from the development of next-generation sequencing (NGS), mitochondrial genomes can be easily acquired and used as reliable molecular markers to investigate phylogenetic relationships within Cerambycidae. Using NGS technology, we obtained 11 mitochondrial genome sequences of Lamiinae species. Based on this newly generated mitochondrial genome dataset matrix, we reconstructed the phylogeny of Lamiinae. The Bayesian Inference and Maximum Likelihood analyses strongly support the monophyly of four tribes (Lamiini, Batocerini, Mesosini, and Saperdini), whereas the tribe Acanthocinini was identified as paraphyletic. Other mitochondrial structural features were also observed: the start codon in the nad1 gene of all 11 mitochondrial genomes is TTG; 17-22 bp intergenic spacers (IGS) with a 'TACTA' motif were found between trnS2 and nad1. Moreover, two long IGS were found in Mesosa myops and Batocera sp. Tandem repeats were found in the IGS of Batocera sp.

Norovirus evolves as one or more distinct clonal populations in immunocompromised hosts.

Noroviruses are an important cause of chronic diarrhea in patients with compromised immune systems. Presently, there are no effective therapies to clear the virus, which can persist for years in the intestinal tract. The goal of our study was to develop a better understanding of the norovirus strains that are associated with these long-term infections. With the remarkable diversity of norovirus strains detected in the immunocompromised patient cohort we studied, it appears that most, if not all, noroviruses circulating in nature may have the capacity to establish a chronic infection when a person is unable to mount an effective immune response. Our work is the most comprehensive genetic data set generated to date in which near full-length genomes from noroviruses associated with chronic infection were analyzed by high-resolution next-generation sequencing. Analysis of this data set led to our discovery that certain patients in our cohort were shedding noroviruses that could be subdivided into distinct haplotypes or populations of viruses that were co-evolving independently. The ability to track haplotypes of noroviruses during chronic infection will allow us to fine-tune our understanding of how the virus adapts and maintains itself in the human host, and how selective pressures such as antiviral drugs can affect these distinct populations.

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.

The worldwide invasion history of a pest ambrosia beetle inferred using population genomics.

Xylosandrus crassiusculus, a fungus-farming wood borer native to Southeastern Asia, is the most rapidly spreading invasive ambrosia species worldwide. Previous studies focusing on its genetic structure suggested the existence of cryptic genetic variation in this species. Yet, these studies used different genetic markers, focused on different geographical areas and did not include Europe. Our first goal was to determine the worldwide genetic structure of this species based on both mitochondrial and genomic markers. Our second goal was to study X. crassiusculus' invasion history on a global level and identify the origins of the invasion in Europe. We used a COI and RAD sequencing design to characterize 188 and 206 specimens worldwide, building the most comprehensive genetic data set for any ambrosia beetle to date. The results were largely consistent between markers. Two differentiated genetic clusters were invasive, albeit in different regions of the world. The markers were inconsistent only for a few specimens found exclusively in Japan. Mainland USA could have acted as a source for further expansion to Canada and Argentina through stepping stone expansion and bridgehead events. We showed that Europe was only colonized by Cluster II through a complex invasion history including several arrivals from multiple origins in the native area, and possibly including bridgehead from the United States. Our results also suggested that Spain was colonized directly from Italy through intracontinental dispersion. It is unclear whether the mutually exclusive allopatric distribution of the two clusters is due to neutral effects or due to different ecological requirements.

The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study

Schizophrenia (SCZ) is highly heterogenous and no subtypes characterizing treatment response or longitudinal course well. Cognitive impairment is a core clinical feature of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive traits is complex, with limited studies of comprehensive epidemiological and genomic evidence. To examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two Swedish samples: a national cohort (14,230 SCZ cases and 3,816,264 controls) and a subsample with comprehensive genetic data (4992 cases and 6009 controls). Population-based analyses confirmed worse cognition as a risk factor for SCZ, and the pedigree and SNP-based genetic correlations were comparable. In the genotyped cases, those with high EDU and premorbid cognitive ability tended to have higher polygenetic risk scores (PRS) of EDU and intelligence and fewer rare exonic variants. Finally, by applying an empirical clustering method, we dissected SCZ cases into four replicable subgroups characterized by EDU and ID. In particular, the subgroup with higher EDU in the national cohort had fewer adverse outcomes including long hospitalization and death. In the genotyped subsample, this subgroup had higher PRS of EDU and no excess of rare genetic burdens than controls. In conclusion, we found extensive evidence of a robust relation between cognitive traits and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.

The Niche of n-of-1 Trials in Precision Medicine for Weight Loss and Obesity Treatment: Back to the Future.

The n-of-1 clinical trials are considered the epitome of individualized health care. They are employed to address differences in treatment response and adverse events between patients, in a comparative effectiveness manner, extending beyond the delivery of horizontal recommendations for all. The n-of-1 design has been applied to deliver precision exercise interventions, through eHealth and mHealth technologies. Regarding personalized and precision medical nutrition therapy, few trials have implemented dietary manipulations and one series of n-of-1 trials has applied comprehensive genetic data to improve body weight. With regard to anti-obesity medication, pharmacogenetic data could be applied using the n-of-1 trial design, although none have been implemented yet. The n-of-1 clinical trials consist of the only tool for the delivery of evidence-based, personalized obesity treatment (lifestyle and pharmacotherapy), reducing non-responders, while tailoring the best intervention to each patient, through "trial and error". Their application is expected to improve obesity treatment and mitigate the epidemic.

Complex reticulate evolution of speckled brush-furred rats (Lophuromys) in the Ethiopian centre of endemism.

The Ethiopian highlands represent a remarkable biodiversity 'hot spot' with a very high number of endemic species, even among vertebrates. Ethiopian representatives of a species complex of speckled brush-furred rats (Lophuromys flavopunctatus sensu lato) inhabit highland habitats ranging from low-elevation forests to Afroalpine grasslands. These may serve as a suitable model for understanding evolutionary processes leading to high genetic and ecological diversity in montane biodiversity hot spots. Here, we analyse the most comprehensive genetic data set of this group, comprising 315 specimens (all nine putative Ethiopian Lophuromys taxa sampled across most of their distribution ranges) genotyped at one mitochondrial and four nuclear markers, and thousands of SNPs from ddRAD sequencing. We performed phylogenetic analyses, delimited species and mapped their distribution and estimated divergence time between species (under the species-tree framework) and mitochondrial lineages. We found significant incongruence between mitochondrial and nuclear phylogenies, most probably caused by multiple interspecific introgression events. We discuss alternative scenarios of Ethiopian Lophuromys evolution, from retention of ancestral polymorphism to hybridization upon secondary contact of partially reproductively isolated lineages leading to reticulate evolution. Finally, we use the diversity of the speckled brush-furred rats for the description of the main biogeographic patterns in the fauna of the Ethiopian highlands.

Genetic analysis and population genetic structure of hard-shelled mussel, Mytilus coruscus Gould 1861 (Mytiloida: Mytilidae) from the coasts of South Korea based on mitochondrial cytochrome oxidase (COI) gene sequences.

Mytilus coruscus Gould, 1861 is a mussel species in the family Mytilidae, native to the Northwest Pacific Ocean, ranging from the East China Sea, the Yellow Sea, and as far as the Peter the Great Gulf in the East Sea. In Korea, this species has been heavily exploited for nutrient-rich food resources and experienced severe reduction in their population. The aim of this study was to investigate the genetic diversity and population structure and to provide baseline data to facilitate the conservation and sustainable use of the vulnerable species M. coruscus in South Korea. Mitochondrial DNA (mtDNA) cytochrome c oxidase I (COI) sequences of 91 adult individuals from four islands and one coastal localities in South Korea were sequenced. We then compared genetic diversity and haplotype data with previously published Chinese wild populations. Mytilus coruscus populations on Korean coasts were found to exhibit high genetic diversity despite concerns regarding recent population reduction. A total of 42 haplotypes were defined by 56 polymorphic sites. High-level genetic diversity was observed on four Island sites (Hd = 0.906-0.955, π = 0.0068-0.0090). The other seashore site represented relatively lower genetic diversity (Hd = 0.529, π = 0.0011) and was genetically differentiated from the others. In a previous study, wild populations on the East China Sea exhibited similarly high genetic diversity as that observed in our study. Additionally, Chinese M. coruscus populations exhibit a distinct regional haplotype distribution pattern while sharing six haplotypes with Korean populations. The results of this study provide insights that further the current understanding regarding the evolution of M. coruscus species and provides comprehensive genetic data to facilitate the development of an effective conservation strategy.

The association between family history and genomic burden with schizophrenia mortality: a Swedish population-based register and genetic sample study

Individuals with schizophrenia (SCZ) have a 2–3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We aimed to identify correlates of SCZ mortality using genetic epidemiological and genetic modelling in two samples: a Swedish national population sample and a genotyped subsample. In the Swedish national population sample followed from the first SCZ treatment contact until emigration, death or end of the follow-up, we investigated a standardised measure of SCZ family history. In a subgroup with comprehensive genetic data, we investigated the impact of common and rare genetic variation. Cox proportional hazards regression was used to estimate the association between various factors and mortality (all and specific causes). A total of 13727 SCZ cases fulfilled criteria for the population-based analyses (1268 deaths, 9.2%). The genomic subset contained 4991 cases (1353 deaths, 27.1%). Somatic mutations associated with clonal hematopoiesis with unknown drivers were associated with all-cause mortality (HR 1.77, 95% CI: 1.26–2.49). No other heritable measures were associated with all-cause mortality nor with any specific causes of death. Future studies in larger, comparable cohorts are warranted to further understand the association between hereditary measures and mortality in SCZ.

Quantification of NG2-positivity for the precise prediction of KMT2A gene rearrangements in childhood acute leukemia.

It has long been known that there is a link between neuron glial antigen 2 (NG2) surface expression and KMT2A gene rearrangements in acute leukemia (AL). However, the exact levels of NG2 positivity that predict the presence of KMT2A rearrangement are not known. The current study focuses on a cohort of 505 pediatric AL patients who showed any level of positive NG2 expression (greater than 1% of cells) for whom comprehensive genetic data were available. NG2 expression was measured as either the percentage of positive cells or the number of molecules on the cell surface. KMT2A gene rearrangements were identified by FISH. The fusion partner was detected with RT-PCR, LDI-PCR or anchored multiplex PCR followed by high-throughput sequencing. KMT2A-positive samples comprised a substantial proportion of the NG2-positive cohort (180 of 505, 36%), with a total of 19 different types of translocation. Despite its occurrence in other AL genetic subgroups, NG2 expression was significantly increased in AL patients with KMT2A rearrangements in terms of both the cell percentage and number of molecules per cell. The threshold levels (TL) for NG2-positivity were established by ROC analysis of the whole cohort and separately for children less than 1 years old and older with lymphoblastic (ALL) and myeloid (AML) leukemia. The lowest TL was defined in infants with ALL (7%), while in older children, the threshold was higher (12%). In AML patients, the situation was reversed, with 28% NG2-positivity in infants and 14% in patients >1 year old. The defined TLs resulted in improved diagnostic performance compared to the conventional thresholds of 10% and 20% for all patient groups.

Genetic evidence further elucidates the history and extent of badger introductions from Great Britain into Ireland.

The colonization of Ireland by mammals has been the subject of extensive study using genetic methods and forms a central problem in understanding the phylogeography of European mammals after the Last Glacial Maximum. Ireland exhibits a depauperate mammal fauna relative to Great Britain and continental Europe, and a range of natural and anthropogenic processes have given rise to its modern fauna. Previous Europe-wide surveys of the European badger (Meles meles) have found conflicting microsatellite and mitochondrial DNA evidence in Irish populations, suggesting Irish badgers have arisen from admixture between human imported British and Scandinavian animals. The extent and history of contact between British and Irish badger populations remains unclear. We use comprehensive genetic data from Great Britain and Ireland to demonstrate that badgers in Ireland's northeastern and southeastern counties are genetically similar to contemporary British populations. Simulation analyses suggest this admixed population arose in Ireland 600–700 (CI 100–2600) years before present most likely through introduction of British badgers by people. These findings add to our knowledge of the complex colonization history of Ireland by mammals and the central role of humans in facilitating it.

Global Diversification Dynamics Since the Jurassic: Low Dispersal and Habitat-Dependent Evolution Explain Hotspots of Diversity and Shell Disparity in River Snails (Viviparidae).

The Viviparidae, commonly known as River Snails, is a dominant group of freshwater snails with a nearly worldwide distribution that reaches its highest taxonomic and morphological diversity in Southeast Asia. The rich fossil record is indicative of a probable Middle Jurassic origin on the Laurasian supercontinent where the group started to diversify during the Cretaceous. However, it remains uncertain when and how the biodiversity hotspot in Southeast Asia was formed. Here, we used a comprehensive genetic data set containing both mitochondrial and nuclear markers and comprising species representing 24 out of 28 genera from throughout the range of the family. To reconstruct the spatiotemporal evolution of viviparids on a global scale, we reconstructed a fossil-calibrated phylogeny. We further assessed the roles of cladogenetic and anagenetic events in range evolution. Finally, we reconstructed the evolution of shell features by estimating ancestral character states to assess whether the appearance of sculptured shell morphologies was driven by major habitat shifts. The molecular phylogeny supports the monophyly of the three subfamilies, the Bellamyinae, Lioplacinae, and Viviparinae, but challenges the currently accepted genus-level classification in several cases. The almost global distribution of River Snails has been influenced both by comparatively ancient vicariance and more recent founder events. In Southeast Asia, Miocene dispersal was a main factor in shaping the modern species distributions. A recurrent theme across different viviparid taxa is that many species living in lentic waters exhibit sculptured shells, whereas only one strongly sculptured species is known from lotic environments. We show that such shell sculpture is habitat-dependent and indeed evolved several times independently in lentic River Snails. Considerably high transition rates between shell types in lentic habitats probably caused the co-occurrence of morphologically distinct shell types in several lakes. In contrast, directional evolution toward smooth shells in lotic habitats, as identified in the present analyses, explains why sculptured shells are rarely found in these habitats. However, the specific factors that promoted changes in shell morphology require further work. [biogeographical analyses; fossil-calibrated phylogeny; fossil-constrained analyses; Southeast Asia; stochastic character mapping.].

Shotgun sequencing decades-old lichen specimens to resolve phylogenomic placement of type material

AbstractNatural history collections, including name-bearing type specimens, are an important source of genetic information. These data can be critical for appropriate taxonomic revisions in cases where the phylogenetic position of name-bearing type specimens needs to be identified, including morphologically cryptic lichen-forming fungal species. Here, we use high-throughput metagenomic shotgun sequencing to generate genome-scale data from decades-old (i.e., more than 30 years old) isotype specimens representing three vagrant taxa in the lichen-forming fungal genusRhizoplaca, including one species and two subspecies. We also use data from high-throughput metagenomic shotgun sequencing to infer the phylogenetic position of an enigmatic collection, originally identified asR. haydenii, that failed to yield genetic data via Sanger sequencing. We were able to construct a 1.64 Mb alignment from over 1200 single-copy nuclear gene regions for theRhizoplacaspecimens. Phylogenomic reconstructions recovered an isotype representingRhizoplaca haydeniisubsp.arbusculawithin a clade comprising other specimens identified asRhizoplaca haydeniisubsp.arbuscula, while an isotype ofR. idahoensiswas recovered within a clade with substantial phylogenetic substructure comprisingRhizoplaca haydeniisubsp.haydeniiand other specimens. Based on these data and morphological differences,Rhizoplaca haydeniisubsp.arbusculais elevated to specific rank asRhizoplaca arbuscula. For the enigmatic collection, we were able to assemble the nearly complete nrDNA cistron and over 50 Mb of the mitochondrial genome. Using these data, we identified this specimen as a morphologically deviant form representingXanthoparmeliaaff.subcumberlandia. This study highlights the power of high-throughput metagenomic shotgun sequencing in generating larger and more comprehensive genetic data from taxonomically important herbarium specimens.

A REVIEW OF THE LIZARDS OF THE ENDEMIC GENUS LANKASCINCUS (REPTILIA: SCINCIDAE: LYGOSOMINAE) FROM SRI LANKA

As a part of an ongoing revision of Sri Lankan scincid lizards, I review the genus Lankascincus Greer on the basis of their morphology and morphometric data. I demonstrate that the long-disputed Sphenomorphus megalops (Annandale) is in fact a Lankascincus species, and a neotype is designated. Lankascincus deraniyagalae Greer and L. munindradasai Wickramasinghe, Rodrigo, Dayawansa, and Jayantha are shown to be junior subjective synonyms of L. fallax (Peters) and L. taprobanensis (Kelaart), respectively. Lankascincus deignani (Taylor) is confined to the forests around Kandy and does not extend to Nuwaraeliya and its environs. Previous records of L. deignani from Nuwaraeliya and surrounding localities are reidentified as L. sripadensis Wickramasinghe, Rodrigo, Dayawansa, and Jayantha. Three groups of Lankascincus species are identified on the basis of their morphology and breeding biology: the fallax, taprobanensis, and dorsicatenatus groups. Each group has a unique combination of characters. Lankascincus taprobanensis is restricted to high-elevational regions (≥1,500 m above mean sea level). Previous records from lower elevations (Sinharaja, Knuckles Range, and Peradeniya) are based on misidentified specimens of other Lankascincus spp. Lankascincus fallax has a wide distribution in Sri Lanka. Lankascincus deignani is restricted to Gannoruwa Forest Reserve and the Ambagamuwa area and is the most endangered skink in Sri Lanka. Ecologically, Lankascincus comprises a largely forest-dwelling species group (L. deignani, L. dorsicatenatus (Deraniyagala), L. gansi Greer, L. greeri Batuwita and Pethiyagoda, L. megalops new combination, and L. taprobanensis) and a group of species that live in altered habitats (L. sripadensis, L. fallax, and L. taylori). The present study confirms that the genus Sphenomorphus Fitzinger is not represented in Sri Lanka. Because of a lack of comprehensive genetic data to support a previously described new family, Ristellidae Hedges for Lankascincus and Ristella Gray, here I assign both genera into a new tribe, Ristellini. Phylogenetic relationships of Lankascincus and Ristella remain unresolved.

Identification of PKD1 and PKD2 gene variants in a cohort of 125 Asian Indian patients of ADPKD

Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD. The pathogenic potential of the variants was evaluated computationally and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.

Social parasitism as an alternative reproductive tactic in a cooperatively breeding cuckoo.

Cooperatively nesting birds are vulnerable to social parasites that lay their eggs in host nests but provide no parental care1-4. Most previous research has focused on the co-evolutionary arms race between host defences and the parasites that attempt to circumvent them5-9, but it remains unclear why females sometimes cooperate and sometimes parasitize, and how parasitic tactics arise in cooperative systems10-12. Here we show that cooperative and parasitic reproductive strategies result in approximately equal fitness pay-offs in the greater ani (Crotophaga major), a long-lived tropical cuckoo, using an 11-year dataset and comprehensive genetic data that enable comparisons of the life-histories of individual females. We found that most females in the population nested cooperatively at the beginning of the breeding season; however, of those birds that had their first nests destroyed, a minority subsequently acted as reproductive parasites. The tendency to parasitize was highly repeatable, which indicates individual specialization. Across years, the fitness pay-offs of the two strategies were approximately equal: females who never parasitized (a 'pure cooperative' strategy) laid larger clutches and fledged more young from their own nests than did birds that both nested and parasitized (a 'mixed' strategy). Our results suggest that the success of parasites is constrained by reproductive trade-offs as well as by host defences, and illustrate how cooperative and parasitic tactics can coexist stably in the same population.

2558. Predicting β-Lactam Resistance Using Whole Genome Sequencing (WGS) in Klebsiella pneumoniae: The Challenge of β-Lactam Inhibitors

BackgroundAntimicrobial susceptibility testing (AST) is the major driver in designing effective therapy. As multiple resistance determinants can demonstrate the same phenotype (e.g., inhibitor resistant [IR], extended spectrum [ES], and carbapenem hydrolyzing [CH] β-lactamases), critical information provided from AST for therapy, stewardship, and infection control is currently lacking. WGS provides more comprehensive genetic data, explaining phenotype, and provides insight into clonality. Efforts are in development that apply novel statistical methods (e.g., PRIMERS I-IV) and machine learning (Sci Reports, 2108, 8, 421) to interpret results accurately and anticipate AST. Using a collection of clinical strains that spanned a 3.5-year period, we tested how well the detection of problematic IR, ES, and CH bla resistance genes predicted phenotype.MethodsFourty-one isolates were chosen for AST from a collection of 1,777 WGS K. pneumoniae. Isolates chosen possessed the following β-lactamases: (9 isolates) NDM; (3) NDM and OXA-48; (5) KPC-8 or KPC-14; (24) with a very complex β-lactamase background (all possessed an inhibitor resistant TEM (IRT), SHV ESBL, +/− CTX-M, and/or +/− KPC). AST was performed using CLSI methods for piperacillin/tazobactam (PIP/TAZO), ceftazidime (CAZ), aztreonam (ATM), ceftazidime/avibactam (CAZ/AVI), CAZ/AVI/ATM, and ceftolozane/tazobactam (TOL/TAZO) by disk diffusion assay.ResultsPresented below. ConclusionIn all cases, blaNDM-1 and blaNDM-1/OXA-48 containing isolates were resistant to CAZ/AVI; the addition of ATM fully restored susceptibility to CAZ/AVI. Surprisingly, clinical K. pneumoniae isolates bearing KPC-8 (V240G) and KPC-14 did not test fully resistant to CAZ/AVI, suggesting a more complex mechanism than the D179Y variant of KPC-3. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Interestingly, TOL/TAZO maintained efficacy in these same complex backgrounds in the absence of NDM, KPC, and SHV-12. As previously shown in PRIMERS I-II, PIP/TAZO resistance was not observed in the majority of isolates as was predicted by the genotype. WGS in K. pneumoniae to predict AST results and potentially guide clinical decisions is improved for novel combinations like CAZ/AVI.Disclosures All authors: No reported disclosures.