scholarly journals Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration

2017 ◽  
Author(s):  
John A. Lees ◽  
Nicholas J. Croucher ◽  
Goldblatt David ◽  
Nosten Francois ◽  
Parkhill Julian ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Low Income ◽  
Genome Wide Association Study ◽  
Sequence Data ◽  
Genomic Variation ◽  
Whole Genome Sequence ◽  
Vaccine Response ◽  
Pneumococcal Carriage ◽  
Genome Wide ◽  
A Genome

AbstractStreptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, and the duration of carriage is an important consideration in modelling transmission dynamics and vaccine response. Existing studies of carriage duration variability are based at the serotype level only, and do not probe variation within lineages or fully quantify interactions with other environmental factors.Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data. By combining these results with whole genome sequence data we estimate that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas host traits accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). For the locus effects, a genome-wide association study identified 16 loci which may have an effect on carriage duration independent of serotype. Hits at a genome-wide level of significance were to prophage sequences, suggesting infection by such viruses substantially affects carriage duration.These results show that both serotype and non-serotype specific effects alter carriage duration in infants and young children and are more important than other environmental factors such as host genetics. This has implications for models of pneumococcal competition and antibiotic resistance, and leads the way for the analysis of heritability of complex bacterial traits.Significance statementOther than serotype, the genetic determinants of pneumococcal carriage duration are unknown. In this study we used longitudinal sampling to measure the duration of carriage in infants, and searched for any associated variation in the pan-genome. While we found that the pathogen genome explains most of the variability in duration, serotype did not fully account for this. Recent theoretical work has proposed the existence of alleles which alter carriage duration to explain the puzzle of continued coexistence of antibiotic-resistant and sensitive strains. Here we have shown that these alleles do exist in a natural population, and also identified candidates for the loci which fulfil this role. Together these findings have implications for future modelling of pneumococcal epidemiology and resistance.

scholarly journals Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
John A Lees ◽  
Nicholas J Croucher ◽  
David Goldblatt ◽  
François Nosten ◽  
Julian Parkhill ◽  
...  
Keyword(s):  
Low Income ◽  
Genome Wide Association Study ◽  
Sequence Data ◽  
Theoretical Models ◽  
Invasive Disease ◽  
Genomic Variation ◽  
Whole Genome Sequence ◽  
Pneumococcal Carriage ◽  
Genome Wide ◽  
Significant Locus

Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.

scholarly journals Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Georgina Samaha ◽  
Claire M. Wade ◽  
Julia Beatty ◽  
Leslie A. Lyons ◽  
Linda M. Fleeman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Sequence Data ◽  
Pancreatic Beta Cell ◽  
Whole Genome Sequence ◽  
Cell Dysfunction ◽  
Genome Wide ◽  
A Genome ◽  
Pathologic Features

Abstract Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case–control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes, ANK1, EPHX2 and LOX2, implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.

scholarly journals Genomic variation across a clinical Cryptococcus population linked to disease outcome

2021 ◽  
Author(s):  
Poppy Channa Sakti Sephton-Clark ◽  
Jennifer Tenor ◽  
Dena Toffaletti ◽  
Nancy Meyers ◽  
Charles Giamberardino ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Sugar Transport ◽  
Genomic Variation ◽  
Clinical Isolates ◽  
Genome Wide ◽  
A Genome ◽  
Gwas Approach

Cryptococcus neoformans is the causative agent of cryptococcosis, a disease with poor patient outcomes, accounting for approximately 180,000 deaths each year. Patient outcomes may be impacted by the underlying genetics of the infecting isolate, however, our current understanding of how genetic diversity contributes to clinical outcomes is limited. Here, we leverage clinical, in vitro growth and genomic data for 284 C. neoformans isolates to identify clinically relevant pathogen variants within a population of clinical isolates from patients with HIV-associated cryptococcosis in Malawi. Through a genome-wide association study (GWAS) approach, we identify variants associated with fungal burden and growth rate. We also find both small and large-scale variation, including aneuploidy, associated with alternate growth phenotypes, which may impact the course of infection. Genes impacted by these variants are involved in transcriptional regulation, signal transduction, glycolysis, sugar transport, and glycosylation. When combined with clinical data, we show that growth within the CNS is reliant upon glycolysis in an animal model, and likely impacts patient mortality, as CNS burden modulates patient outcome. Additionally, we find genes with roles in sugar transport are under selection in the majority of these clinical isolates. Further, we demonstrate that two hypothetical proteins identified by GWAS impact virulence in animal models. Our approach illustrates links between genetic variation and clinically relevant phenotypes, shedding light on survival mechanisms within the CNS and pathways involved in this persistence.

scholarly journals Genome-wide association mapping for agronomic and quality traits in foxtail millet

2019 ◽  
Author(s):  
Yanhong Lou ◽  
Yun Chen ◽  
Zhihao Liu ◽  
Mingjie Sun ◽  
Fei Han ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Foxtail Millet ◽  
Significant Snps ◽  
Genomic Variation ◽  
Genome Wide Association ◽  
Quality Traits ◽  
Nucleotide Polymorphisms ◽  
High Quality ◽  
Genome Wide ◽  
A Genome

Abstract Background: Foxtail millet [Setaria italica (L.) P. Beauv.] is a particularly important cereal and fodder crop in arid and semi-arid regions. The genomic variation and alleles underpinning agronomic and quality traits are important for foxtail millet improvement. To better understand the diversity of foxtail millet and facilitate the genetic dissection of its agronomic and quality traits, we used high-quality single nucleotide polymorphisms (SNPs) to perform a genome-wide association study (GWAS). Results: Using genotyping-by-sequencing, 107 foxtail millet accessions were sequenced, and further analysis revealed 72,181 high-quality SNPs, of which 53 were significantly associated with 15 agronomic and quality traits. These SNPs were distributed across the nine chromosomes of foxtail millet; 44 were located in intergenic regions, whereas one and eight SNPs were located in exon and intron regions, respectively. The GWAS revealed that 28 SNPs were associated with a single trait. Conclusions: For some of the significant SNPs, favourable genotypes showed pyramiding effects for several traits. The 53 loci identified in this study will therefore be useful for breeding programs aimed at foxtail millet improvement.

scholarly journals Characterizing rare and low-frequency height-associated variants in the Japanese population

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Masato Akiyama ◽  
Kazuyoshi Ishigaki ◽  
Saori Sakaue ◽  
Yukihide Momozawa ◽  
Momoko Horikoshi ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Rare Variants ◽  
Sequence Data ◽  
Low Frequency ◽  
European Population ◽  
Genotype Imputation ◽  
Whole Genome Sequence ◽  
General Tendency ◽  
Phenotypic Variance ◽  
A Genome

Abstract Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and low-frequency variants associated with height, we construct a reference panel (N = 3,541) for genotype imputation by integrating the whole-genome sequence data from 1,037 Japanese with that of the 1000 Genomes Project, and perform a genome-wide association study in 191,787 Japanese. We report 573 height-associated variants, including 22 rare and 42 low-frequency variants. These 64 variants explain 1.7% of the phenotypic variance. Furthermore, a gene-based analysis identifies two genes with multiple height-increasing rare and low-frequency nonsynonymous variants (SLC27A3 and CYP26B1; PSKAT-O < 2.5 × 10−6). Our analysis shows a general tendency of the effect sizes of rare variants towards increasing height, which is contrary to findings among Europeans, suggesting that height-associated rare variants are under different selection pressure in Japanese and European populations.

scholarly journals Pigment Intensity in Dogs is Associated with a Copy Number Variant Upstream of KITLG

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 75 ◽  
Author(s):  
Kalie Weich ◽  
Verena Affolter ◽  
Daniel York ◽  
Robert Rebhun ◽  
Robert Grahn ◽  
...  
Keyword(s):  
Copy Number ◽  
Genome Wide Association Study ◽  
Coat Color ◽  
Sequence Data ◽  
Copy Number Variant ◽  
Color Variation ◽  
Domestic Dog ◽  
Whole Genome Sequence ◽  
Hair Color ◽  
A Genome

Dogs exhibit a wide variety of coat color types, and many genes have been identified that control pigment production, appearance, and distribution. Some breeds, such as the Nova Scotia Duck Tolling Retriever (NSDTR), exhibit variation in pheomelanin pigment intensity that is not explained by known genetic variants. A genome-wide association study comparing light red to dark red in the NSDTR identified a significantly associated region on canine chromosome 15 (CFA 15:23 Mb–38 Mb). Coverage analysis of whole genome sequence data from eight dogs identified a 6 kb copy number variant (CNV) 152 kb upstream of KITLG. Genotyping with digital droplet PCR (ddPCR) confirmed a significant association between an increased copy number with the dark-red coat color in NSDTR (p = 6.1 × 10−7). The copy number of the CNV was also significantly associated with coat color variation in both eumelanin and pheomelanin-based Poodles (p = 1.5 × 10−8, 4.0 × 10−9) and across other breeds. Moreover, the copy number correlated with pigment intensity along the hair shaft in both pheomelanin and eumelanin coats. KITLG plays an important role in melanogenesis, and variants upstream of KITLG have been associated with coat color variation in mice as well as hair color in humans consistent with its role in the domestic dog.

scholarly journals Genome-wide association study in the pseudocereal quinoa reveals selection pattern typical for crops with a short breeding history

2020 ◽  
Author(s):  
Dilan S. R. Patiranage ◽  
Elodie Rey ◽  
Nazgol Emrani ◽  
Gordon Wellman ◽  
Karl Schmid ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Agronomic Traits ◽  
Sequence Data ◽  
Genome Wide Association ◽  
Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Modern Breeding ◽  
Orphan Crop

AbstractQuinoa germplasm preserves useful and substantial genetic variation, yet it remains untapped due to a lack of implementation of modern breeding tools. We have integrated field and sequence data to characterize a large diversity panel of quinoa. Whole-genome sequencing of 310 accessions revealed 2.9 million polymorphic high confidence SNP loci. Highland and Lowland quinoa were clustered into two main groups, with FST divergence of 0.36 and fast LD decay of 6.5 and 49.8 Kb, respectively. A genome-wide association study uncovered 600 SNPs stably associated with 17 agronomic traits. Two candidate genes are associated with thousand seed weight, and a resistance gene analog is associated with downy mildew resistance. We also identified pleiotropically acting loci for four agronomic traits that are highly responding to photoperiod hence important for the adaptation to different environments. This work demonstrates the use of re-sequencing data of an orphan crop, which is partially domesticated to rapidly identify marker-trait association and provides the underpinning elements for genomics-enabled quinoa breeding.

Sign in / Sign up

Export Citation Format

Share Document