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 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.

A Genetic Model To Predict Response to Glatiramer Acetate Developed from a Genome Wide Association Study (GWAS) (IN3-2.003)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. IN3-2.003-IN3-2.003
Author(s):  
F. Macciardi ◽  
J. Cohen ◽  
M. Comabella Lopez ◽  
G. Comi ◽  
G. Cutter ◽  
...  
Keyword(s):  
Association Study ◽  
Glatiramer Acetate ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study of Gestational Diabetes Mellitus in Korean Women

Diabetes ◽  
2012 ◽  
Vol 61 (2) ◽  
pp. 531-541 ◽  
Author(s):  
S. H. Kwak ◽  
S.-H. Kim ◽  
Y. M. Cho ◽  
M. J. Go ◽  
Y. S. Cho ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Korean Women ◽  
Genome Wide ◽  
A Genome

Abstract 051: Genome-wide Association Study Identifies 12 Loci for Habitual Consumption of Bitter and Sweet Beverages

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Victor W Zhong ◽  
Sandra Sanchez-Roige ◽  
Peter Kraft ◽  
Rob M Van Dam ◽  
Daniel I Chasman ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Taste Perception ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Multiple Snps ◽  
Genome Wide ◽  
A Genome

Introduction: Widely consumed beverages (e.g., soft drinks, coffee, tea) are critical sources of energy, added sugar and phytochemicals and are associated with obesity and chronic disease. Taste perception and preferences are highly heritable and strong determinants of food and beverage choice. We aimed to identify novel loci underlying habitual bitter and sweet beverage intake. Methods: We performed a genome-wide association study (GWAS) of self-reported bitter and sweet beverage intake in participants of European ancestry in the UK Biobank. Diet was assessed via multiple 24-h diet recalls (n=84703, subset) or questionnaire (n=335909, all). Bitter beverage intake was the sum of coffee, tea and grapefruit juice. Sweet beverage intake was the sum of artificially and sugar sweetened beverages and other fruit juice. Multivariable linear regression under an additive genetic model was applied. GW-significant (P < 5х10 -8 ) SNPs were followed-up for replication in independent studies of European ancestry. Results: Multiple SNPs spanning 11 loci were associated with bitter beverage intake (P <5х10 -8 , Table 1), and at least 5 of them reflected the caffeine content of coffee and tea. Multiple SNPs in the obesity candidate gene FTO were associated with sweet beverage intake (P <5х10 -8 ). The effect size per allele ranged from 0.02 to 0.2 cup per day. Loci in/near AHR, CYP1A2, and FTO were associated with both bitter and sweet beverage intake but in opposite directions. Replication efforts are ongoing. So far, associations at all loci, except 1q25.2 and 2q36.2, were replicated (P range: 0.04 to 1.8x10 -8 ) in independent studies (n=17322) which provided 80% power for replicating 8 of these 12 loci at P=0.05. Conclusions: Loci linked to caffeine metabolism and obesity predisposition rather than taste are major determinants of beverage intake. These and other identified loci have been linked to chronic disease and risk factors, suggesting causal or pleiotropic effects. Our findings have potential public health and methodological implications.

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.

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