ResearchPad - genetic-mapping https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection]]> https://www.researchpad.co/article/elastic_article_15749 Congenital cytomegalovirus (cCMV) infection is the most common intrauterine infection. A non-specific immune response is the first line of host defense mechanism against human cytomegalovirus (HCMV). There is limited data on associations between Single Nucleotide Polymorphisms (SNPs) in genes involving innate immunity and the risk and clinical manifestation of cCMV infection. The aim of the study was to investigate association between selected SNPs in genes encoding cytokines and cytokine receptors, and predisposition to cCMV infection including symptomatic course of disease and symptoms. A panel of eight SNPs: IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140 was analyzed in 233 infants (92 cCMV-infected and 141 healthy controls). Associations between genotyped SNPs and predisposition to cCMV infection and symptoms were analyzed. The association analysis was performed using SNPStats software. No statistically significant association was found between any genotyped SNPs and predisposition to cCMV infection and symptomatic course of disease. In relation to particular symptoms, polymorphism of IL12B rs3212227 was linked to decreased risk of prematurity (OR = 0.37;95%CI,0.14–0.98;p = 0.025), while polymorphism of IL1B rs16944 was linked to reduced risk of splenomegaly (OR = 0.36;95%CI,0.14–0.98; p = 0.034) in infants with cCMV infection. An increased risk of thrombocytopenia was associated with IL28B rs12979860 polymorphism (OR = 2.55;95%CI,1.03–6.32;p = 0.042), while hepatitis was associated with SNP of TLR4rs4986791 (OR = 7.80;95%CI,1.49–40,81; p = 0.024). This is the first study to demonstrate four new associations between SNPs in selected genes (IL1B, IL12B, IL28B, TLR4) and particular symptoms in cCMV disease. Further studies on the role of SNPs in the pathogenesis of cCMV infection and incorporation of selected SNPs in the clinical practice might be considered in the future.

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<![CDATA[Genome-wide association study of partial resistance to sclerotinia stem rot of cultivated soybean based on the detached leaf method]]> https://www.researchpad.co/article/elastic_article_15721 Sclerotinia stem rot (SSR) is a devastating fungal disease that causes severe yield losses of soybean worldwide. In the present study, a representative population of 185 soybean accessions was selected and utilized to identify the quantitative trait nucleotide (QTN) of partial resistance to soybean SSR via a genome-wide association study (GWAS). A total of 22,048 single-nucleotide polymorphisms (SNPs) with minor allele frequencies (MAF) > 5% and missing data < 3% were used to assess linkage disequilibrium (LD) levels. Association signals associated with SSR partial resistance were identified by two models, including compressed mixed linear model (CMLM) and multi-locus random-SNP-effect mixed linear model (mrMLM). Finally, seven QTNs with major effects (a known locus and six novel loci) via CMLM and nine novel QTNs with minor effects via mrMLM were detected in relation to partial resistance to SSR, respectively. One of all the novel loci (Gm05:14834789 on Chr.05), which was co-located by these two methods, might be a stable one that showed high significance in SSR partial resistance. Additionally, a total of 71 major and 85 minor candidate genes located in the 200-kb genomic region of each peak SNP detected by CMLM and mrMLM were found, respectively. By using a gene-based association, a total of six SNPs from three major effects genes and eight SNPs from four minor effects genes were identified. Of them, Glyma.18G012200 has been characterized as a significant element in controlling fungal disease in plants.

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<![CDATA[Simultaneous SNP selection and adjustment for population structure in high dimensional prediction models]]> https://www.researchpad.co/article/elastic_article_14653 This work addresses a recurring challenge in the analysis and interpretation of genetic association studies: which genetic variants can best predict and are independently associated with a given phenotype in the presence of population structure? Not controlling confounding due to geographic population structure, family and/or cryptic relatedness can lead to spurious associations. Much of the existing research has therefore focused on modeling the association between a phenotype and a single genetic variant in a linear mixed model with a random effect. However, this univariate approach may miss true associations due to the stringent significance thresholds required to reduce the number of false positives and also ignores the correlations between markers. We propose an alternative method for fitting high-dimensional multivariable models, which selects SNPs that are independently associated with the phenotype while also accounting for population structure. We provide an efficient implementation of our algorithm and show through simulation studies and real data examples that our method outperforms existing methods in terms of prediction accuracy and controlling the false discovery rate.

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<![CDATA[Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus]]> https://www.researchpad.co/article/elastic_article_14643 Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM).Materials and methodsWe have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1–2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum.ResultsAfter adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567–6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = −5.478, 95% CI: -8.315 to −2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = −6.319, 95% CI: −9.466 to −3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes.ConclusionsThis study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results. ]]> <![CDATA[Genetic variation and phylogeographic structure of <i>Spodoptera exigua</i> in western China based on mitochondrial DNA and microsatellite markers]]> https://www.researchpad.co/article/elastic_article_14552 The beet armyworm, Spodoptera exigua, is a significant agricultural pest of numerous crops and has caused serious economic losses in China. To effectively control this pest, we analyzed its genetic variation, population genetic structure and demographic history. We used mitochondrial DNA (mtDNA) fragments of the cytochrome oxidase subunit I (COI) and eight nuclear microsatellite loci to investigate genetic diversity and population genetic structure of S. exigua populations at 14 sampling sites in western China. Both mtDNA and microsatellite data indicated low levels of genetic diversity among all populations. A moderate genetic differentiation among some S. exigua populations was detected. Neighbor-joining dendrograms, STRUCTURE, and principal coordinate analysis (PCoA) revealed two genetically distinct groups: the KEL group and the remaining population group. Isolation by distance (IBD) results showed a weak significant correlation between geographic distance and genetic differentiation. Haplotype networks, neutrality testing, and mismatch distribution analysis indicated that the beet armyworm experienced a recent rapid expansion without a recent genetic bottleneck in western China. Thus, the results of this population genetic study can help with the development of strategies for managing this highly migratory pest.

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<![CDATA[Genetic diversity of <i>Echinococcus multilocularis</i> and <i>Echinococcus granulosus sensu lato</i> in Kyrgyzstan: The A2 haplotype of <i>E</i>. <i>multilocularis</i> is the predominant variant infecting humans]]> https://www.researchpad.co/article/elastic_article_13871 Analysis of the genetic variability in Echinococcus species from different endemic countries have contributed to the knowledge in the taxonomy and phylogeography of these parasites. The most important species of this genus, Echinococcus granulosus sensu lato and Echinococcus multilocularis, co-exist in Kyrgyzstan causing serious public health issues. E. granulosus s.l. causes cystic echinococcosis and E. multilocularis is the causative agent of alveolar echinococcosis. The most relevant finding of our study is the identification of the cob/nad2/cox1 A2 haplotype of E. multilocularis as the most commonly found in humans and dogs. However, it remains unknown if this variant of E. multilocularis, based on genetic differences in mitochondrial genes, presents differences in virulence which could have contributed to the emergence of alveolar echinococcosis in Kyrgyzstan. The results also show a number of non-previously described genetic variants of E. multilocularis and E. granulosus s.s.

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<![CDATA[Interaction between host genes and <i>Mycobacterium tuberculosis</i> lineage can affect tuberculosis severity: Evidence for coevolution?]]> https://www.researchpad.co/article/elastic_article_13824 Susceptibility to tuberculosis (TB) is affected by genetic variation in both the human host and the causative bacterium, Mycobacterium tuberculosis. However, prior studies of the genetics of each species have not explained a large part of TB risk. The possibility exists that risk can be better estimated from patterns of variation in the two species as a unit, such that some combinations provide increased risk, or in the presence of TB, increased disease severity. We hypothesized that alleles in the two species that have co-existed for long periods are more likely to reduce disease severity so as to promote prolonged co-occurrence. We tested this by studying TB severity in two patient cohorts from Uganda for which paired MTB-human DNA were available. We examined severity, as measured by the Bandim TBscore, and assessed whether there was an interaction between MTB lineage and SNPs in the host with this metric. Our results indicate that the most recent TB lineage (L4.6/Uganda) when found together with an ancestral allele in SLC11A1 resulted in more severe disease. This finding is consistent with the conclusion that MTB and human have coevolved to modulate TB severity.

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<![CDATA[Adaptive genetic diversity and evidence of population genetic structure in the endangered Sierra Madre Sparrow (<i>Xenospiza baileyi</i>)]]> https://www.researchpad.co/article/elastic_article_11235 The magnitude and distribution of genetic diversity through space and time can provide useful information relating to evolutionary potential and conservation status in threatened species. In assessing genetic diversity in species that are of conservation concern, several studies have focused on the use of Toll-like receptors (TLRs). TLRs are innate immune genes related to pathogen resistance, and polymorphisms may reflect not only levels of functional diversity, but may also be used to assess genetic diversity within and among populations. Here, we combined four potentially adaptive markers (TLRs) with one mitochondrial (COI) marker to evaluate genetic variation in the endangered Sierra Madre Sparrow (Xenospiza baileyi). This species offers an ideal model to investigate population and evolutionary genetic processes that may be occurring in a habitat restricted endangered species with disjunct populations (Mexico City and Durango), the census sizes of which differ by an order of magnitude. TLRs diversity in the Sierra Madre Sparrow was relatively high, which was not expected given its two small, geographically isolated populations. Genetic diversity was different (but not significantly so) between the two populations, with less diversity seen in the smaller Durango population. Population genetic structure between populations was due to isolation and different selective forces acting on different TLRs; population structure was also evident in COI. Reduction of genetic diversity in COI was observed over 20 years in the Durango population, a result likely caused by habitat loss, a factor which may be the main cause of diversity decline generally. Our results provide information related to the ways in which adaptive variation can be altered by demographic changes due to human-mediated habitat alterations. Furthermore, our findings may help to guide conservation schemes for both populations and their restricted habitat.

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<![CDATA[Evidence for both sequential mutations and recombination in the evolution of kdr alleles in Aedes aegypti]]> https://www.researchpad.co/article/N8479e8f6-b6ad-4aa7-91b1-bf6bde90184a

Background

Aedes aegypti is a globally distributed vector of human diseases including dengue, yellow fever, chikungunya, and Zika. Pyrethroid insecticides are the primary means of controlling adult A. aegypti populations to suppress arbovirus outbreaks, but resistance to pyrethroid insecticides has become a global problem. Mutations in the voltage-sensitive sodium channel (Vssc) gene are a major mechanism of pyrethroid resistance in A. aegypti. Vssc resistance alleles in A. aegypti commonly have more than one mutation. However, our understanding of the evolutionary dynamics of how alleles with multiple mutations arose is poorly understood.

Methodology/Principal findings

We examined the geographic distribution and association between the common Vssc mutations (V410L, S989P, V1016G/I and F1534C) in A. aegypti by analyzing the relevant Vssc fragments in 25 collections, mainly from Asia and the Americas. Our results showed all 11 Asian populations had two types of resistance alleles: 1534C and 989P+1016G. The 1534C allele was more common with frequencies ranging from 0.31 to 0.88, while the 989P+1016G frequency ranged from 0.13 to 0.50. Four distinct alleles (410L, 1534C, 410L+1534C and 410L+1016I+1534C) were detected in populations from the Americas. The most common was 410L+1016I+1534C with frequencies ranging from 0.50 to 1.00, followed by 1534C with frequencies ranging from 0.13 to 0.50. Our phylogenetic analysis of Vssc supported multiple independent origins of the F1534C mutation. Our results indicated the 410L+1534C allele may have arisen by addition of the V410L mutation to the 1534C allele, or by a crossover event. The 410L+1016I+1534C allele was the result of one or two mutational steps from a 1534C background.

Conclusions/Significance

Our data corroborated previous geographic distributions of resistance mutations and provided evidence for both recombination and sequential accumulation of mutations contributing to the molecular evolution of resistance alleles in A. aegypti.

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<![CDATA[Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil]]> https://www.researchpad.co/article/N0a09703b-e69a-40d3-8ae4-dfe23e56b45d

Introduction

The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil.

Methods

The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software.

Results

Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world.

Conclusion

Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.

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<![CDATA[A framework for gene mapping in wheat demonstrated using the Yr7 yellow rust resistance gene]]> https://www.researchpad.co/article/N8aa5bdf2-6390-43c2-aef2-b7a76659179a

We used three approaches to map the yellow rust resistance gene Yr7 and identify associated SNPs in wheat. First, we used a traditional QTL mapping approach using a double haploid (DH) population and mapped Yr7 to a low-recombination region of chromosome 2B. To fine map the QTL, we then used an association mapping panel. Both populations were SNP array genotyped allowing alignment of QTL and genome-wide association scans based on common segregating SNPs. Analysis of the association panel spanning the QTL interval, narrowed the interval down to a single haplotype block. Finally, we used mapping-by-sequencing of resistant and susceptible DH bulks to identify a candidate gene in the interval showing high homology to a previously suggested Yr7 candidate and to populate the Yr7 interval with a higher density of polymorphisms. We highlight the power of combining mapping-by-sequencing, delivering a complete list of gene-based segregating polymorphisms in the interval with the high recombination, low LD precision of the association mapping panel. Our mapping-by-sequencing methodology is applicable to any trait and our results validate the approach in wheat, where with a near complete reference genome sequence, we are able to define a small interval containing the causative gene.

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<![CDATA[Genome-wide haplotype-based association analysis of key traits of plant lodging and architecture of maize identifies major determinants for leaf angle: hapLA4]]> https://www.researchpad.co/article/5c89773ed5eed0c4847d27e7

Traits related to plant lodging and architecture are important determinants of plant productivity in intensive maize cultivation systems. Motivated by the identification of genomic associations with the leaf angle, plant height (PH), ear height (EH) and the EH/PH ratio, we characterized approximately 7,800 haplotypes from a set of high-quality single nucleotide polymorphisms (SNPs), in an association panel consisting of tropical maize inbred lines. The proportion of the phenotypic variations explained by the individual SNPs varied between 7%, for the SNP S1_285330124 (located on chromosome 9 and associated with the EH/PH ratio), and 22%, for the SNP S1_317085830 (located on chromosome 6 and associated with the leaf angle). A total of 40 haplotype blocks were significantly associated with the traits of interest, explaining up to 29% of the phenotypic variation for the leaf angle, corresponding to the haplotype hapLA4.04, which was stable over two growing seasons. Overall, the associations for PH, EH and the EH/PH ratio were environment-specific, which was confirmed by performing a model comparison analysis using the information criteria of Akaike and Schwarz. In addition, five stable haplotypes (83%) and 15 SNPs (75%) were identified for the leaf angle. Finally, approximately 62% of the associated haplotypes (25/40) did not contain SNPs detected in the association study using individual SNP markers. This result confirms the advantage of haplotype-based genome-wide association studies for examining genomic regions that control the determining traits for architecture and lodging in maize plants.

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<![CDATA[Biogeography of the endosymbiotic dinoflagellates (Symbiodiniaceae) community associated with the brooding coral Favia gravida in the Atlantic Ocean]]> https://www.researchpad.co/article/5c8c1937d5eed0c484b4d1a6

Zooxanthellate corals live in symbiosis with phototrophic dinoflagellates of the family Symbiodiniaceae, enabling the host coral to dwell in shallow, nutrient-poor marine waters. The South Atlantic Ocean is characterized by low coral diversity with high levels of endemism. However, little is known about coral–dinoflagellate associations in the region. This study examined the diversity of Symbiodiniaceae associated with the scleractinian coral Favia gravida across its distributional range using the ITS-2 marker. This brooding coral endemic to the South Atlantic can be found across a wide range of latitudes and longitudes, including the Mid-Atlantic islands. Even though it occurs primarily in shallower environments, F. gravida is among the few coral species that live in habitats with extreme environmental conditions (high irradiance, temperature, and turbidity) such as very shallow tide pools. In the present study, we show that F. gravida exhibits some degree of flexibility in its symbiotic association with zooxanthellae across its range. F. gravida associates predominantly with Cladocopium C3 (ITS2 type Symbiodinium C3) but also with Symbiodinium A3, Symbiodinium linucheae (ITS2 type A4), Cladocopium C1, Cladocopium C130, and Fugacium F3. Symbiont diversity varied across biogeographic regions (Symbiodinium A3 and S. linucheae were found in the Tropical Eastern Atlantic, Cladocopium C1 in the Mid-Atlantic, and other subtypes in the Southwestern Atlantic) and was affected by local environmental conditions. In addition, Symbiodiniaceae diversity was highest in a southwestern Atlantic oceanic island (Rocas Atoll). Understanding the relationship between corals and their algal symbionts is critical in determining the factors that control the ecological niches of zooxanthellate corals and their symbionts, and identifying host-symbiont pairs that may be more resistant to environmental changes.

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<![CDATA[Ser96Ala genetic variant of the human histidine-rich calcium-binding protein is a genetic predictor of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation]]> https://www.researchpad.co/article/5c897742d5eed0c4847d2858

Background

Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca2+ handling has a considerable effect on AF recurrence. The histidine-rich calcium-binding protein (HRC) genetic single nucleotide polymorphism (SNP), rs3745297 (T>G, Ser96Ala), is known to cause a sarcoplasmic reticulum Ca2+ leak. We investigated the association between HRC Ser96Ala and AF recurrence after RFCA in paroxysmal AF (PAF) patients.

Methods and results

We enrolled PAF patients who underwent RFCA (N = 334 for screening and N = 245 for replication) and were genotyped for HRC SNP (rs3745297). The patient age was younger and rate of diabetes and hypertension lower in the PAF patients with Ser96Ala than in those without (TT/TG/GG, 179/120/35; 64±10/60±12/59±13 y, P = 0.001; 18.5/ 9.2/8.6%, P = 0.04 and 66.1/50.0/37.1%, P = 0.001, respectively). During a mean 19 month follow-up, 57 (17.1%) patients suffered from AF recurrences. The rate of an Ser96Ala was significantly higher in patients with AF recurrence than in those without in the screening set (allele frequency model: odds ratio [OR], 1.80; P = 0.006). We also confirmed this significant association in the replication set (OR 1.74; P = 0.03) and combination (P = 0.0008). A multivariate analysis revealed that the AF duration, sinus node dysfunction, and HRC Ser96Ala were independent predictors of an AF recurrence (hazard ratio [HR], 1.04, P = 0.037; HR 2.42, P = 0.018; and HR 2.66, P = 0.007, respectively).

Conclusion

HRC SNP Ser96Ala is important as a new genetic marker of AF recurrence after RFCA.

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<![CDATA[HCV transmission in high-risk communities in Bulgaria]]> https://www.researchpad.co/article/5c882406d5eed0c4846395b0

Background

The rate of HIV infection in Bulgaria is low. However, the rate of HCV-HIV-coinfection and HCV infection is high, especially among high-risk communities. The molecular epidemiology of those infections has not been studied before.

Methods

Consensus Sanger sequences of HVR1 and NS5B from 125 cases of HIV/HCV coinfections, collected during 2010–2014 in 15 different Bulgarian cities, were used for preliminary phylogenetic evaluation. Next-generation sequencing (NGS) data of the hypervariable region 1 (HVR1) analyzed via the Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to evaluate genetic heterogeneity and possible transmission linkages. Links between pairs that were below and above the established genetic distance threshold, indicative of transmission, were further examined by generating k-step networks.

Results

Preliminary genetic analyses showed predominance of HCV genotype 1a (54%), followed by 1b (20.8%), 2a (1.4%), 3a (22.3%) and 4a (1.4%), indicating ongoing transmission of many HCV strains of different genotypes. NGS of HVR1 from 72 cases showed significant genetic heterogeneity of intra-host HCV populations, with 5 cases being infected with 2 different genotypes or subtypes and 6 cases being infected with 2 strains of same subtype. GHOST revealed 8 transmission clusters involving 30 cases (41.7%), indicating a high rate of transmission.

Four transmission clusters were found in Sofia, three in Plovdiv, and one in Peshtera. The main risk factor for the clusters was injection drug use. Close genetic proximity among HCV strains from the 3 Sofia clusters, and between HCV strains from Peshtera and one of the two Plovdiv clusters confirms a long and extensive transmission history of these strains in Bulgaria.

Conclusions

Identification of several HCV genotypes and many HCV strains suggests a frequent introduction of HCV to the studied high-risk communities. GHOST detected a broad transmission network, which sustains circulation of several HCV strains since their early introduction in the 3 cities. This is the first report on the molecular epidemiology of HIV/HCV coinfections in Bulgaria.

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<![CDATA[A polyploid admixed origin of beer yeasts derived from European and Asian wine populations]]> https://www.researchpad.co/article/5c88240dd5eed0c48463962a

Strains of Saccharomyces cerevisiae used to make beer, bread, and wine are genetically and phenotypically distinct from wild populations associated with trees. The origins of these domesticated populations are not always clear; human-associated migration and admixture with wild populations have had a strong impact on S. cerevisiae population structure. We examined the population genetic history of beer strains and found that ale strains and the S. cerevisiae portion of allotetraploid lager strains were derived from admixture between populations closely related to European grape wine strains and Asian rice wine strains. Similar to both lager and baking strains, ale strains are polyploid, providing them with a passive means of remaining isolated from other populations and providing us with a living relic of their ancestral hybridization. To reconstruct their polyploid origin, we phased the genomes of two ale strains and found ale haplotypes to both be recombinants between European and Asian alleles and to also contain novel alleles derived from extinct or as yet uncharacterized populations. We conclude that modern beer strains are the product of a historical melting pot of fermentation technology.

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<![CDATA[Origins and geographic diversification of African rice (Oryza glaberrima)]]> https://www.researchpad.co/article/5c897765d5eed0c4847d2be9

Rice is a staple food for the majority of the world’s population. Whereas Asian rice (Oryza sativa) has been extensively studied, the exact origins of African rice (Oryza glaberrima) are still contested. Previous studies have supported either a centric or a non-centric geographic origin of African rice domestication. Here we review the evidence for both scenarios through a critical reassessment of 206 whole genome sequences of domesticated and wild African rice. While genetic diversity analyses support a severe bottleneck caused by domestication, signatures of recent and strong positive selection do not unequivocally point to candidate domestication genes, suggesting that domestication proceeded differently than in Asian rice–either by selection on different alleles, or different modes of selection. Population structure analysis revealed five genetic clusters localising to different geographic regions. Isolation by distance was identified in the coastal populations, which could account for parallel adaptation in geographically separated demes. Although genome-wide phylogenetic relationships support an origin in the eastern cultivation range followed by diversification along the Atlantic coast, further analysis of domestication genes shows distinct haplotypes in the southwest—suggesting that at least one of several key domestication traits might have originated there. These findings shed new light on an old controversy concerning plant domestication in Africa by highlighting the divergent roots of African rice cultivation, including a separate centre of domestication activity in the Guinea Highlands. We thus suggest that the commonly accepted centric origin of African rice must be reconsidered in favour of a non-centric or polycentric view.

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<![CDATA[A novel polymorphism in the fatty acid desaturase 2 gene (Fads2): A possible role in the basal metabolic rate]]> https://www.researchpad.co/article/5c818e86d5eed0c484cc247a

Fatty acyl composition of cell membrane lipids, particularly the abundance of highly unsaturated docosahexaenoic fatty acid (22:6n-3, DHA), is likely to be an important predictor of basal metabolic rate (BMR). Our study was performed using two lines of laboratory mice divergently selected for either high or low BMR. We describe a novel single nucleotide polymorphism in the Fads2 gene encoding Δ6-desaturase, a key enzyme in the metabolic pathways of polyunsaturated fatty acids (PUFAs). The allele frequencies of Fads2 were significantly different in both lines of mice. The analysis of genetic distances revealed that the genetic differentiation between the two studied lines developed significantly faster at the Fads2 locus than it did at neutral loci. Such a pattern suggests that the Fads2 polymorphism is related to the variation in BMR, i.e. the direct target of selection. The Fads2 polymorphism significantly affected abundance of several PUFAs; however, the differences in PUFA composition between lines were compatible with the difference in frequency of Fads2 alleles only for DHA. We hypothesize that the polymorphism in the Fads2 gene affects the BMR through modification of DHA abundance in cell membranes. This may be the first example of a significant link between a polymorphism in a gene responsible for fatty acyl composition and variation in BMR.

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<![CDATA[IL-10 polymorphisms +434T/C, +504G/T, and -2849C/T may predispose to tubulointersititial nephritis and uveitis in pediatric population]]> https://www.researchpad.co/article/5c75ac83d5eed0c484d08944

Background

Tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are likely to be autoimmune diseases. Based on previous studies, adults with isolated idiopathic uveitis have polymorphisms in interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) genes. We aimed to evaluate the presence of IL-10 and TNF-α polymorphisms in a nationwide cohort of pediatric TIN/TINU patients.

Methods

Single nucleotide polymorphisms in IL-10 (+434T/C, +504G/T, -1082G/A, -2849C/T) and in TNFα (-308G/A, -238G/A, -857C/T) genes were genotyped in 30 well-defined pediatric patients with idiopathic TIN/TINU syndrome. Control group frequencies for these SNPs were obtained from 393 independent Finnish subjects.

Results

The homozygous minor allele in IL-10 +434T (rs2222202) and IL-10+504G (rs3024490) was found in all patients with TIN or TINU syndrome while the frequency of these minor alleles in the control population was 44% and 23%, respectively (p <0.001). In IL-10 SNP -2849 (rs6703630) a significant difference was found with genotype TT in all patients (p = 0.004) and in subgroups with TINU syndrome (p = 0.017) and TINU syndrome with chronic uveitis (p = 0.01) compared to reference population. There were no statistical differences in any of the studied TNF-α genotypes between TIN/TINU patients and control population.

Conclusions

A significant difference in the frequency of IL-10+434T and +504G alleles was found between TIN/TINU patients and control population. Genotype -2849TT was more frequently present in patients with TINU syndrome than in the reference subjects. Genetic variation in the inflammatory mediators may predispose to autoimmune nephritis and uveitis.

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<![CDATA[Rectifying long-standing misconceptions about the ρ statistic for molecular dating]]> https://www.researchpad.co/article/5c75ac76d5eed0c484d08825

When divided by a given mutation rate, the ρ (rho) statistic provides a simple estimator of the age of a clade within a phylogenetic tree by averaging the number of mutations from each sample in the clade to its root. However, a long-standing critique of the use of ρ in genetic dating has been quite often cited. Here we show that the critique is unfounded. We demonstrate by a formal mathematical argument and illustrate with a simulation study that ρ estimates are unbiased and also that ρ and maximum likelihood estimates do not differ in any systematic fashion. We also demonstrate that the claim that the associated confidence intervals commonly estimate the uncertainty inappropriately is flawed since it relies on a means of calculating standard errors that is not used by any other researchers, whereas an established expression for the standard error is largely unproblematic. We conclude that ρ dating, alongside approaches such as maximum likelihood (ML) and Bayesian inference, remains a useful tool for genetic dating.

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