Population-specific Manner Research Articles

Population-specific responses to developmental temperature in the arboviral vector Aedes albopictus: Implications for climate change.

The increase of environmental temperature due to current global warming is not only favouring the expansion of the distribution range of many insect species, but it is also changing their phenology. Insect phenology is tightly linked to developmental timing, which is regulated by environmental temperatures. However, the degree to which the effects of developmental temperatures extend across developmental stages and their inter-stage relationships have not been thoroughly quantified in mosquitoes. Here, we used the mosquito Aedes albopictus, which is an aggressive invasive species and an arboviral vector, to study how developmental temperature influences fitness across developmental stages, thermal traits, energy reserves, transcriptome and Wolbachia prevalence in laboratory-reared populations originally collected from either temperate or tropical regions. We show that hatchability, larval and pupal viability and developmental speed are strongly influenced by temperature, and these effects extend to wing length, body mass, longevity and content of water, protein and lipids in adults in a population-specific manner. On the contrary, neither adult thermal preference nor heat resistance significantly change with temperature. Wolbachia density was generally lower in adult mosquitoes reared at 18°C than at other tested temperatures, and transcriptome analysis showed enrichment for functions linked to stress responses (i.e. cuticle proteins and chitin, cytochrome p450 and heat shock proteins) in mosquitoes reared at both 18 and 32°C. Our data showed an overall reduced vector fitness performance when mosquitoes were reared at 32°C, and the absence of isomorphy in the relationship between developmental stages and temperature in the laboratory population deriving from larvae collected in northern Italy. Altogether, these results have important implications for reliable model projections of the invasion potentials of Ae. albopictus and its epidemiological impact.

ODP575 Single-cell analysis reveals heterogeneity of mouse mammary gland fibroblasts with discrete functions, estrogen responses, differentiation, and communications with epithelium.

Abstract Mammary gland is an essential organ for milk production. It continues to develop after birth under the influence of ovarian hormones, especially estrogen. Among its cellular components, fibroblasts are recognized as an important player for mammary gland organization. Although human mammary gland fibroblasts have been classified into two subtypes based on histological localizations and different marker expressions (i. e., interlobular and intralobular fibroblasts), their detailed characteristics and functions are still limited. Moreover, despite the importance of experimental mouse models for studying mammary gland biology, heterogeneity of mouse mammary gland fibroblasts has not been fully defined. Here, we performed single-cell RNA sequencing (scRNA-seq) to determine cellular populations and their potential contributions to mammary gland organization. Based on the comprehensive gene expression profiles at a single cell level, we identified two major clusters of the mouse mammary gland fibroblasts. One of the major clusters showed the highly specific expression of Dpp4 gene, which is a known marker for human interlobular fibroblasts, and the upregulation of the inflammatory response gene signature. The other major cluster was consisted of three subclusters without Dpp4 expression, which suggested the distinct contributions to adipogenesis and/or ECM modeling in mammary gland stroma. Through the histological validation, we defined these two major subsets as "DPP4+" and "DPP4-" fibroblasts. Since our scRNA-seq was performed on two different ovarian hormone-depleted mouse models followed with hormone treatments, we evaluated the effect of the hormones, especially estrogen. The results demonstrated that the estrogen treatment altered the gene expression profiles of the DPP4+ and a subcluster of the DPP4- fibroblasts in a population-specific manner. Estrogen upregulated interferon-regulated genes and ECM genes in these fibroblast populations, respectively, but not typical estrogen-regulated genes, even in the ERα+ DPP4+ fibroblasts. To define these mammary gland fibroblasts better, we integrated our datasets with a recently established "steady-state mouse fibroblasts atlas" (1) as well as four other scRNA-seq datasets containing normal mouse mammary gland fibroblasts. Using this integrated dataset, we revealed the directional differentiation among the mammary gland fibroblasts, going from the fibroblasts and branching toward the DPP4- fibroblasts with more specialized functions. Moreover, the cell-cell interaction analysis combined with a mammary epithelium dataset from our previous publication (2) indicated possible cell-type-specific communications between mammary gland fibroblasts and epithelial cells. In conclusion, this study provided a comprehensive view of mouse mammary gland fibroblast biology at the single-cell level. Our findings would provide fundamental insights for further investigations on the roles of different fibroblast populations in mammary gland organization and pathological conditions, such as breast cancer. Reference: (1) Buechler et al., Nature. 2021 May;593(7860): 575–579. (2) Saeki et al., Commun Biol. 2021 Jun;4(1): 1–16. Presentation: No date and time listed

The Difference in the Bacterial Attachment among Pratylenchus neglectus Populations and Its Effect on the Nematode Infection.

Different bacterial isolates attach to the cuticle of plant-parasitic nematodes, affecting their interactions with the host plant. Nematode populations differ in their genetic and cuticle structures, causing variable interactions with host plants and natural enemies. In the current study, attachment assays were carried out to compare the attachment of soil bacteria in general and the bacterial isolate of Rothia sp. in particular among geographically diverse populations of Pratylenchus neglectus. Biological and molecular assays were further conducted to examine the effect of Rothia attachment on nematode penetration into barley roots and to sequence the fatty acid- and retinol-binding gene (Pn-far-1). The results showed that nematode populations of P. neglectus differed in their bacterial attachment. Soil bacteria and Rothia sp. attached specifically to the cuticle of P. neglectus and did so differently among the nematode populations. Rothia attachment caused a reduction in the infectivity of three nematode populations in barley roots. The sequencing of the far-1 gene revealed genetic variability within and among P. neglectus populations. In conclusion, the interaction between P. neglectus and their bacterial attachers occurs in a population-specific manner, elucidating an essential aspect of using biological agents to manage plant-parasitic nematodes. Key Message: 1. Geographically diverse populations of the root lesion nematode Pratylenchus neglectus differed in the soil bacterial communities attached to their cuticles. 2. The bacterial isolate of Rothia sp. attached to the cuticle of P. neglectus and reduced its penetration into the host plant in a population-specific manner. 3. The fatty acid- and retinol-binding gene (far-1) varied within and among P. neglectus populations with their different bacterial attachment.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n=11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n=9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n=11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

Single-Cell Transcriptomics Identifies Heterogeneity of Mouse Mammary Gland Fibroblasts With Distinct Functions, Estrogen Responses, Differentiation Processes, and Crosstalks With Epithelium.

Fibroblasts have been shown to be one of the essential players for mammary gland organization. Here, we identify two major types of mouse mammary gland fibroblasts through single-cell RNA sequencing analysis: Dpp4 + fibroblasts and Dpp4 - fibroblasts. Each population exhibits unique functional characteristics as well as discrete localization in normal mouse mammary glands. Remarkably, estrogen, a crucial mediator of mammary gland organization, alters the gene expression profiles of fibroblasts in a population-specific manner, without distinct activation of estrogen receptor signaling. Further integrative analysis with the inclusion of five other publicly available datasets reveals a directional differentiation among the mammary gland fibroblast populations. Moreover, the combination with the mouse mammary epithelium atlas allows us to infer multiple potential interactions between epithelial cells and fibroblasts in mammary glands. This study provides a comprehensive view of mouse mammary gland fibroblasts at the single-cell level.

A lexicon-based method for detecting eye diseases on microblogs

ABSTRACT This paper explored the feasibility of detecting eye diseases on microblogs. A lexicon-based approach was developed to provide an early recognition of common eye disease from social media platforms. The data were obtained using Twitter free streaming Application Programming Interface (API). A cluster analysis was applied to extract instances that share similar characteristics. We extracted three types of emotions (positive, negative, and neutral) from users’ messages (tweets) using SentiStrength. A time-series method was used to determine the applicability of predicting emotional changes over a period of seven months. The relevant disease symptoms were extracted using Apriori algorithm with prediction accuracy of 98.89%. This study offers a timely and effective method that can be implemented to help healthcare decision makers and researchers reduce the spread of eye diseases in a population specific manner.

Intronic LINE-1 insertion in SLCO1B3 as a highly prevalent cause of rotor syndrome in East Asian population.

Rotor syndrome is caused by digenic loss-of-function variants in SLCO1B1 and SLCO1B3 but only a few studies have reported co-occurring inactivating variants from both genes. A rotor syndrome-causing long interspersed element-1 (LINE-1) insertion in SLCO1B3 had been reported to be highly prevalent in the Japanese population but there has been no additional report. In spite of its known association with various human diseases, LINE-1 is hard to detect with current sequencing technologies. In this study, we aimed to devise a method to screen the LINE-1 insertion variant and investigate the frequency of this variant in various populations. A chimeric sequence, thatwas generated by concatenating the reference sequence at the junction and a part of inserted LINE-1 sequence, was searched from 725 raw sequencing data files. In cases containing the chimeric sequence, confirmatory long-range PCR and gap-PCR were performed. In total, 95 (13.1%) of 725 patients were positive for the chimeric sequence, and all were confirmed to have the SLCO1B3 LINE-1 insertion by PCR-based tests. The same chimeric sequence was searched from the 1000 Genomes Project data repository and the carrier frequency was remarkably high in the East Asian populations (10.1%), especially in Southern Han Chinese (18.5%), but almost absent in other populations. This SLCO1B3 LINE-1 insertion should be screened in a population-specific manner under suspicion of Rotor syndrome and the methods proposed in this study would enable this in a simple way.

OPRD1 SNPs associated with opioid addiction are cis-eQTLs for the phosphatase and actin regulator 4 gene, PHACTR4, a mediator of cytoskeletal dynamics

Several OPRD1 intronic variants were associated with opioid addiction (OD) in a population-specific manner. This follow-up study aims to further characterize the OPRD1 haplotype pattern of the risk variants in different populations and apply in silico analysis to identify potential causal variants. A population-specific haplotype pattern was revealed based on six OPRD1 eQTL SNPs and five common haplotypes were identified in a sample of European ancestry (CEU). A European-specific haplotype (‘Hap 3’) that includes SNPs previously associated with OD and is tagged by SNP rs2236861 is more common in subjects with OD. It is quite common (10%) in CEU but is absent in the African sample (YRI) and extends upstream of OPRD1. SNP rs2236857 is most probably a non-causal variant in LD with the causal SNP/s in a population-specific manner. The study provides an explanation for the lack of association in African Americans, despite its high frequency in this population. OD samples homozygous for ‘Hap 3’ were reanalyzed using a denser coverage of the region and revealed at least 25 potentially regulatory SNPs in high LD. Notably, GTEx data indicate that some of the SNPs are eQTLs for the upstream phosphatase and actin regulator 4 (PHACTR4), in the cortex, and others are eQTLs for OPRD1 and the upstream lncRNA ENSG00000270605, in the cerebellum. The study highlights the limitation of single SNP analysis and the sensitivity of association studies of OPRD1 to a genetic background. It proposes a long-range functional connection between OPRD1 and PHACTR4. PHACTR4, a mediator of cytoskeletal dynamics, may contribute to drug addiction by modulating synaptic plasticity.

MTHFR 1298A>C Substitution is a Strong Candidate for Analysis in Recurrent Pregnancy Loss: Evidence from 14,289 Subjects.

We undertook meta-analyses on MTHFR 1298A>C substitution for critically evaluating its association with recurrent pregnancy loss (RPL). MTHFR genotype data for 5888 cases and 8401 controls from 39 studies were pooled to perform thismeta-analyses. Genotype data were screened, scrutinized, pooled, analysed and subjected to sensitivity analysis to carefully evaluate the association between MTHFR 1298A>C and recurrent pregnancy loss. Genetic associations were sought using dominant, recessive and co-dominant models of genetic testingwith odds ratio and 95%Confidence interval (CI) as the effect measures. Further analyses were undertaken by classifying the studies into Caucasian and East Asian sub-groups. Genetic heterogeneity was tested before pooling the data across studies. For assessing publication bias, Egger's intercept test was undertaken. We found a significant association of 1298A>C substitution with increased risk of RPL in the dominant (P=0.000; OR = 1.58; 95% CI =1.25-1.99) as well as recessive (P=0.000; OR = 1.66; 95% CI =1.25-2.20) models. In sub-group analysis, we observed a significant association of the polymorphism with RPL in the Caucasian populations using dominant (P=0.000; OR = 1.98; 95% CI =1.42-2.76) and recessive (P=0.000; OR = 2.20; 95% CI =1.49-3.24) models. However, this substitution showed no association with RPL in the East Asian populations (P=0.149; OR = 1.187; 95% CI =0.94-1.50). MTHFR 1298A>C substitution shows association with the risk of recurrent pregnancy loss. The association is in a population-specific manner with the substitution being a strong risk factor only in the Caucasian populations.

T-cell responses to sequentially emerging viral escape mutants shape long-term HIV-1 population dynamics.

HIV-1 strains harboring immune escape mutations can persist in circulation, but the impact of selection by multiple HLA alleles on population HIV-1 dynamics remains unclear. In Japan, HIV-1 Reverse Transcriptase codon 135 (RT135) is under strong immune pressure by HLA-B*51:01-restricted and HLA-B*52:01-restricted T cells that target a key epitope in this region (TI8; spanning RT codons 128-135). Major population-level shifts have occurred at HIV-1 RT135 during the Japanese epidemic, which first affected hemophiliacs (via imported contaminated blood products) and subsequently non-hemophiliacs (via domestic transmission). Specifically, threonine accumulated at RT135 (RT135T) in hemophiliac and non-hemophiliac HLA-B*51:01+ individuals diagnosed before 1997, but since then RT135T has markedly declined while RT135L has increased among non-hemophiliac individuals. We demonstrated that RT135V selection by HLA-B*52:01-restricted TI8-specific T-cells led to the creation of a new HLA-C*12:02-restricted epitope TN9-8V. We further showed that TN9-8V-specific HLA-C*12:02-restricted T cells selected RT135L while TN9-8T-specific HLA-C*12:02-restricted T cells suppressed replication of the RT135T variant. Thus, population-level accumulation of the RT135L mutation over time in Japan can be explained by initial targeting of the TI8 epitope by HLA-B*52:01-restricted T-cells, followed by targeting of the resulting escape mutant by HLA-C*12:02-restricted T-cells. We further demonstrate that this phenomenon is particular to Japan, where the HLA-B*52:01-C*12:02 haplotype is common: RT135L did not accumulate over a 15-year longitudinal analysis of HIV sequences in British Columbia, Canada, where this haplotype is rare. Together, our observations reveal that T-cell responses to sequentially emerging viral escape mutants can shape long-term HIV-1 population dynamics in a host population-specific manner.

Analysis of Haplotypic Variation and Deletion Polymorphisms Point to Multiple Archaic Introgression Events, Including from Altai Neanderthal Lineage.

The time, extent, and genomic effect of the introgressions from archaic humans into ancestors of extant human populations remain some of the most exciting venues of population genetics research in the past decade. Several studies have shown population-specific signatures of introgression events from Neanderthals, Denisovans, and potentially other unknown hominin populations in different human groups. Moreover, it was shown that these introgression events may have contributed to phenotypic variation in extant humans, with biomedical and evolutionary consequences. In this study, we present a comprehensive analysis of the unusually divergent haplotypes in the Eurasian genomes and show that they can be traced back to multiple introgression events. In parallel, we document hundreds of deletion polymorphisms shared with Neanderthals. A locus-specific analysis of one such shared deletion suggests the existence of a direct introgression event from the Altai Neanderthal lineage into the ancestors of extant East Asian populations. Overall, our study is in agreement with the emergent notion that various Neanderthal populations contributed to extant human genetic variation in a population-specific manner.

Abstract B077: Ribosomal RNAs are fragmented into short RNAs in a manner that depends on a person’s sex, population origin, and race: implications for health disparities and personalized medicine

Abstract Ribosomal RNAs (rRNAs) are the most abundant RNAs in eukaryotic cells. rRNAs combine with ribosomal proteins to form the scaffold for the small and large subunits of the ribosomes. There are six distinct rRNAs: four are encoded by the nuclear and two by the mitochondrial genome. Deep sequencing showed that short RNAs, known as “rRNA-derived fragments” or rRFs, arise from all six rRNAs. The accumulated evidence suggests that rRFs have key functional roles. Various studies showed that rRFs can modulate intracellular ATP levels, participate in the response to stress, affect ERK signaling, and are required for DNA repair. Moreover, rRFs can be loaded on Argonaute thereby entering the RNAi pathway and regulating transcript abundance. To systematically study rRFs, we developed a computational pipeline and used it to analyze the short RNA profiles of lymphoblastoid cell lines obtained from 434 healthy participants of the 1000 Genomes Project. The 434 individuals represent five human populations, and two races. Men and women are represented evenly in each of the five populations. We analyzed the rRF profiles for each of the six rRNAs in turn, and separately for the five populations and two sexes. Across the 434 individuals, we identified more than 18,000 rRFs each with a normalized abundance ≥ 10 reads per million. Each of the six rRNAs gives rise to ‘clouds of rRFs’ whose identities and abundances differ characteristically from each rRNA to the next. We found that the clouds of rRFs are produced in a population-specific, race-specific, and sex-specific manner. Like samples, i.e. samples belonging to the same sex and population group, produce rRFs with the same identities and relative abundances, which suggests that rRFs are produced in a regimented manner by currently unknown processes. Preliminary analyses of rRFs in primary cancer samples and cell lines led to similar results. Northern blotting allowed us to independently confirm several of our computational findings. Our laboratory has long focused on the study of microRNAs (miRNAs), miRNA isoforms (isomiRs), transfer RNAs (tRNAs), and tRNA-derived fragments (tRFs) in health and disease. IsomiRs and tRFs play important roles in cells by modulating transcript abundance through Argonaute-loading, translation-stalling, decoying of RNA binding proteins, etc. We were first to show that isomiRs and tRFs are produced constitutively in human tissues and that their profiles depend on a person’s sex, population origin, and race, as well as on tissue type, tissue state, and disease. We also reported sex- and/or race-dependent differences for multiple cancers, including those of the prostate, bladder, lung, kidney, and breast. Through the current study, we show for a third category of short regulatory RNAs, the rRFs, that they too depend on personal attributes such as sex, population origin, and race. The finding and the large number of rRFs have implications for the study of health disparities, in cancer and other diseases, and for efforts to practice personalized medicine. Citation Format: Tess Cherlin, Rogan Magee, Yi Jing, Phillipe Loher, Venetia Pliatsika, Isidore Rigoutsos. Ribosomal RNAs are fragmented into short RNAs in a manner that depends on a person’s sex, population origin, and race: implications for health disparities and personalized medicine [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B077.

The elephant in the lung: Integrating lineage-tracing, molecular markers, and single cell sequencing data to identify distinct fibroblast populations during lung development and regeneration

During lung development, the mesenchyme and epithelium are dependent on each other for instructive morphogenic cues that direct proliferation, cellular differentiation and organogenesis. Specification of epithelial and mesenchymal cell lineages occurs in parallel, forming cellular subtypes that guide the formation of both transitional developmental structures and the permanent architecture of the adult lung. While epithelial cell types and lineages have been relatively well-defined in recent years, the definition of mesenchymal cell types and lineage relationships has been more challenging. Transgenic mouse lines with permanent and inducible lineage tracers have been instrumental in identifying lineage relationships among epithelial progenitor cells and their differentiation into distinct airway and alveolar epithelial cells. Lineage tracing experiments with reporter mice used to identify fibroblast progenitors and their lineage trajectories have been limited by the number of cell specific genes and the developmental timepoint when the lineage trace was activated. In this review, we discuss major developmental mesenchymal lineages, focusing on time of origin, major cell type, and other lineage derivatives, as well as the transgenic tools used to find and define them. We describe lung fibroblasts using function, location, and molecular markers in order to compare and contrast cells with similar functions. The temporal and cell-type specific expression of fourteen “fibroblast lineage” genes were identified in single-cell RNA-sequencing data from LungMAP in the LGEA database. Using these lineage signature genes as guides, we clustered murine lung fibroblast populations from embryonic day 16.5 to postnatal day 28 (E16.5-PN28) and generated heatmaps to illustrate expression of transcription factors, signaling receptors and ligands in a temporal and population specific manner.

(My Microbiome) Would Walk 10,000miles: Maintenance and Turnover of Microbial Communities in Introduced Dung Beetles.

Host-associated microbes facilitate diverse biotic and abiotic interactions between hosts and their environments. Experimental alterations of host-associated microbial communities frequently decrease host fitness, yet much less is known about if and how host-microbiome interactions are altered by natural perturbations, such as introduction events. Here, we begin to assess this question in Onthophagus dung beetles, a species-rich and geographically widely distributed genus whose members rely on vertically transmitted microbiota to support normal development. Specifically, we investigated to what extent microbiome community membership shifts during host introduction events and the relative significance of ancestral associations and novel environmental conditions in the structuring of microbial communities of introduced host species. Our results demonstrate that both evolutionary history and local environmental forces structure the microbial communities of these animals, but that their relative importance is shaped by the specific circumstances that characterize individual introduction events. Furthermore, we identify microbial taxa such as Dysgonomonas that may constitute members of the core Onthophagus microbiome regardless of host population or species, but also Wolbachia which associates with Onthophagus beetles in a species or even population-specific manner. We discuss the implications of our results for our understanding of the evolutionary ecology of symbiosis in dung beetles and beyond.

Ribosomal RNA fragmentation into short RNAs (rRFs) is modulated in a sex- and population of origin-specific manner

BackgroundThe advent of next generation sequencing (NGS) has allowed the discovery of short and long non-coding RNAs (ncRNAs) in an unbiased manner using reverse genetics approaches, enabling the discovery of multiple categories of ncRNAs and characterization of the way their expression is regulated. We previously showed that the identities and abundances of microRNA isoforms (isomiRs) and transfer RNA-derived fragments (tRFs) are tightly regulated, and that they depend on a person’s sex and population origin, as well as on tissue type, tissue state, and disease type. Here, we characterize the regulation and distribution of fragments derived from ribosomal RNAs (rRNAs). rRNAs form a group that includes four (5S, 5.8S, 18S, 28S) rRNAs encoded by the human nuclear genome and two (12S, 16S) by the mitochondrial genome. rRNAs constitute the most abundant RNA type in eukaryotic cells.ResultsWe analyzed rRNA-derived fragments (rRFs) across 434 transcriptomic datasets obtained from lymphoblastoid cell lines (LCLs) derived from healthy participants of the 1000 Genomes Project. The 434 datasets represent five human populations and both sexes. We examined each of the six rRNAs and their respective rRFs, and did so separately for each population and sex. Our analysis shows that all six rRNAs produce rRFs with unique identities, normalized abundances, and lengths. The rRFs arise from the 5′-end (5′-rRFs), the interior (i-rRFs), and the 3′-end (3′-rRFs) or straddle the 5′ or 3′ terminus of the parental rRNA (x-rRFs). Notably, a large number of rRFs are produced in a population-specific or sex-specific manner. Preliminary evidence suggests that rRF production is also tissue-dependent. Of note, we find that rRF production is not affected by the identity of the processing laboratory or the library preparation kit.ConclusionsOur findings suggest that rRFs are produced in a regimented manner by currently unknown processes that are influenced by both ubiquitous as well as population-specific and sex-specific factors. The properties of rRFs mirror the previously reported properties of isomiRs and tRFs and have implications for the study of homeostasis and disease.

The Impact of Natural Selection on the Evolution and Function of Placentally Expressed Galectins.

Immunity genes have repeatedly experienced natural selection during mammalian evolution. Galectins are carbohydrate-binding proteins that regulate diverse immune responses, including maternal–fetal immune tolerance in placental pregnancy. Seven human galectins, four conserved across vertebrates and three specific to primates, are involved in placental development. To comprehensively study the molecular evolution of these galectins, both across mammals and within humans, we conducted a series of between- and within-species evolutionary analyses. By examining patterns of sequence evolution between species, we found that primate-specific galectins showed uniformly high substitution rates, whereas two of the four other galectins experienced accelerated evolution in primates. By examining human population genomic variation, we found that galectin genes and variants, including variants previously linked to immune diseases, showed signatures of recent positive selection in specific human populations. By examining one nonsynonymous variant in Galectin-8 previously associated with autoimmune diseases, we further discovered that it is tightly linked to three other nonsynonymous variants; surprisingly, the global frequency of this four-variant haplotype is ∼50%. To begin understanding the impact of this major haplotype on Galectin-8 protein structure, we modeled its 3D protein structure and found that it differed substantially from the reference protein structure. These results suggest that placentally expressed galectins experienced both ancient and more recent selection in a lineage- and population-specific manner. Furthermore, our discovery that the major Galectin-8 haplotype is structurally distinct from and more commonly found than the reference haplotype illustrates the significance of understanding the evolutionary processes that sculpted variants associated with human genetic disease.

Types and frequency of fingerprint minutiae in individuals of Igbo and Yoruba ethnic groups of Nigeria

The population distribution of fingerprint minutiae is necessary to improve efficiency of fingerprints in identifying individuals in a population-specific manner. The objective of the study was to determine the distribution of different types of minutiae fingerprint feature in two Nigerian ethnic populations. Fingerprints from forty-four (44) Igbo individuals and forty-four (44) Yoruba individuals, both of Nigeria were collected using a manual impression method that uses ink pad and paper. Of all the minutiae types considered, bifurcations and convergences accounted for 54.85% of the study’s total minutiae counts (TMC). This study shows that the Igbo ethnic group consistently have higher count of all minutiae types and higher total minutiae counts for both hands statistically significant at P<0.001. We found association between gender and minutiae distribution in some minutiae types including fragment/point or dot (FP), overlap (OL) and break (BR). This work revealed important variations among individuals from the two ethnic groups on the distribution and variability of minutiae in Nigeria populations. Keywords: Dermatoglyphics, fingerprints, forensic, Igbo, minutiae, Nigeria, Yoruba.

Single-nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine.

Pemphigus vulgaris (PV) is a rare autoimmune blistering disorder, which could affect both skin and mucosal surfaces. There is increasing evidence that genetics plays a critical role in PV development, severity and prognosis. Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people and have been widely evaluated in most diseases. However, there are few studies regarding the roles of SNPs in the PV. Here, we reviewed both pathogenic and protective roles of the SNPs in non-HLA genes regarding the PV. Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population-specific manner. Moreover, SNPs in glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, including rs11745958, rs17209237, rs33388, rs7701443 as well as rs116855232 at NUDT15, seem to be associated with therapeutic outcomes in PV patients. Additionally, variations in the other genes involved in the drugs' metabolisms, pharmacokinetics and pharmacodynamics such as rs396991 in FCGR3A gene could be used for the prediction of clinical response to drugs and side effects. Taken together, SNPs seem to be valuable tools for better management of PV patients. Further studies need to be conducted to evaluate SNPs in genes that control immune responses and apoptosis.

Adaptations of early development to local spawning temperature in anadromous populations of pike (Esox lucius)

BackgroundIn the wake of climate change many environments will be exposed to increased and more variable temperatures. Knowledge about how species and populations respond to altered temperature regimes is therefore important to improve projections of how ecosystems will be affected by global warming, and to aid management. We conducted a common garden, split-brood temperature gradient (4.5 °C, 9.7 °C and 12.3 °C) experiment to study the effects of temperature in two populations (10 families from each population) of anadromous pike (Esox lucius) that normally experience different temperatures during spawning. Four offspring performance measures (hatching success, day degrees until hatching, fry survival, and fry body length) were compared between populations and among families.ResultsTemperature affected all performance measures in a population-specific manner. Low temperature had a positive effect on the Harfjärden population and a negative effect on the Lervik population. Further, the effects of temperature differed among families within populations.ConclusionsThe population-specific responses to temperature indicate genetic differentiation in developmental plasticity between populations, and may reflect an adaptation to low temperature during early fry development in Harfjärden, where the stream leading up to the wetland dries out relatively early in the spring, forcing individuals to spawn early. The family-specific responses to temperature treatment indicate presence of genetic variation for developmental plasticity (G x E) within both populations. Protecting between- and within-population genetic variation for developmental plasticity and high temperature-related adaptive potential of early life history traits will be key to long-term viability and persistence in the face of continued climate change.

SAT-191 WHOLE GENOME ANALYSIS OF ABORIGINAL AUSTRALIANS REVEALS VARIANTS ASSOCIATED WITH KIDNEY DISEASE

Indigenous Australians in remote areas are up to 20 times more likely to develop end stage renal disease than non-Indigenous Australians. Remote communities in Western Australia and Northern Territory are experiencing an escalating renal disease epidemic, such as the Tiwi people who are at a high risk of kidney disease, significantly reducing their life expectancy. Genetic factors are though to affect 36-75% of kidney function and chronic kidney disease (CKD) progression. Population-scale genomic studies have established that the frequencies of specific disease-associated alleles vary substantially between populations, and identifying these alleles can offer insights useful for preventing, diagnosing, and treating these diseases in a population-specific manner. The Tiwi people have participated in a 25 year longitudinal study of chronic disease incidence, progression, treatments, and outcomes, offering a wealth of biochemical and physical phenotyping data. We have previously shown that there is a strong genetic component to kidney disease among the Tiwi people, but the exact alleles involved remained uncertain. In the present study, we conducted a whole genome sequencing (WGS) analysis of 120 individuals from the Tiwi islands and identified several genetic loci associated with traits linked to kidney disease, including serum creatinine, EGFR, and uric acid levels. Study participants were categorized as cases (n=60) or controls (n=60) for kidney disease, based on albumin creatinine ratio and estimated glomerular filtration rate. We sequenced the whole genomes of 120 participants at 30x coverage using HiSeq X Series, aligned reads to the reference human genome using the BWA tool, and then employed the GATK pipeline to identify genetic variants. Six computational approaches were used to assess the functional impact of genetic variants (SIFT, Polyphen2, MutationTaster2, LRT, FATHMM, and PROVEAN), and we probed the association of identified variants with kidney disease using the ClinVar, GAD, and GWAS databases. MAF (Minor Allele Frequency) analysis was carried out using VCFtools and in-house scripts. Notably, we utilized a customized database of genes associated with kidney disease curated from literature sources and currently available diagnostic gene panels. We identified 12,507,010 variants, of which 19,899 were predicted to be deleterious. We observed an at least 2-fold allelic difference between cases and controls for 569 polymorphic variants, of which 16% were present in the 1000 Genome data (<=1 MAF), and 73% were not present in the 1000G dataset. Further focused kidney disease gene analysis showed that 8 variants were associated with kidney disease. We observed a remarkably high frequency (3-fold) in alleles associated with Alport syndrome in cases relative to controls. Our results suggest population-specific CKD risk alleles exist in the Tiwi people that were not detected by previous lower coverage population genomics studies, and we are collecting samples to validate these findings. These novel variants offer a potential means of screening individuals in this population to identify those at risk of kidney disease. The combination of these genomic data with the available 25 years of compiled longitudinal clinical data represents an invaluable resource that can be harnessed to improve health among all Indigenous Australian populations.