Genome-wide Association Study Of Resistance Research Articles

Large-Sample Genome-Wide Association Study of Resistance to Retained Placenta in U.S. Holstein Cows.

A genome-wide association study of resistance to retained placenta (RETP) using 632,212 Holstein cows and 74,747 SNPs identified 200 additive effects with p-values < 10-8 on thirteen chromosomes but no dominance effect was statistically significant. The regions of 87.61-88.74 Mb of Chr09 about 1.13 Mb in size had the most significant effect in LOC112448080 and other highly significant effects in CCDC170 and ESR1, and in or near RMND1 and AKAP12. Four non-ESR1 genes in this region were reported to be involved in ESR1 fusions in humans. Chr23 had the largest number of significant effects that peaked in SLC17A1, which was involved in urate metabolism and transport that could contribute to kidney disease. The PKHD1 gene contained seven significant effects and was downstream of another six significant effects. The ACOT13 gene also had a highly significant effect. Both PKHD1 and ACOT13 were associated with kidney disease. Another highly significant effect was upstream of BOLA-DQA2. The KITLG gene of Chr05 that acts in utero in germ cell and neural cell development, and hematopoiesis was upstream of a highly significant effect, contained a significant effect, and was between another two significant effects. The results of this study provided a new understanding of genetic factors underlying RETP in U.S. Holstein cows.

Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii

Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods.

Genome-wide association study of resistance to anthracnose in pepper (Capsicum chinense) germplasm

BackgroundAnthracnose is a fungal disease caused by Colletotrichum spp. that has a significant impact on worldwide pepper production. Colletotrichum scovillei is the most common pathogenic anthracnose-causing species in the Republic of Korea.ResultsThe resistances of 197 pepper (Capsicum chinense) accessions deposited in Korea’s National Agrobiodiversity Center were evaluated for their response against the virulent pathogens Colletotrichum acutatum isolate ‘KSCa-1’ and C. scovillei isolate ‘Hana’) in the field and in vitro methods for three consecutive years (2018 to 2020). The severity of the disease was recorded and compared between inoculation methods. Six phenotypically resistant pepper accessions were selected based on three years of disease data. All of the selected resistant pepper accessions outperformed the control resistant pepper in terms of resistance (PI 594,137). A genome-wide association study (GWAS) was carried out to identify single nucleotide polymorphisms (SNPs) associated with anthracnose resistance. An association analysis was performed using 53,518 SNPs and the disease score of the 2020 field and in vitro experiment results. Both field and in vitro experiments revealed 25 and 32 significantly associated SNPs, respectively. These SNPs were found on all chromosomes except Ch06 and Ch07 in the field experiment, whereas in the in vitro experiment they were found on all chromosomes except Ch04 and Ch11.ConclusionIn this study, six resistant C. chinense accessions were selected. Additionally, in this study, significantly associated SNPs were found in a gene that codes for a protein kinase receptor, such as serine/threonine-protein kinase, and other genes that are known to be involved in disease resistance. This may strengthen the role of these genes in the development of anthracnose resistance in Capsicum spp. As a result, the SNPs discovered to be strongly linked in this study can be used to identify a potential marker for selecting pepper material resistant to anthracnose, which will assist in the development of resistant varieties.

Genome-wide Association Study of Resistance to Mastitis in Czech Holstein Cattle

Clinical mastitis is an inflammatory disease of the mammary gland that largely impacts dairy farming profitability and welfare. Globally, a massive scientific effort is being made to elucidate the possible link of certain genotypes to the susceptibility to this disease. After data pruning controlling for genotype missingness, minor allele frequency, and population stratification, 51 557 SNPs from 1 042 animals have been analysed using the general linear model (GLM). Two SNPs, BTA-121769-no-rs and BTB-00265951, have demonstrated statistically significant associations (–log10(p) &gt; 6.0134), both located on the chromosome BTA6. The detected SNPs have been annotated within a reference genome. They have been found to lie outside of transcribed regions but within the vicinity of genes essential for the immune response. This finding further supports the case for their significance in the resistance to mastitis. In addition, 14 relatively weaker associations (–log10(p) &gt; 4) have been observed across chromosomes BTA1, 2, 9, 14, 19, 24 and 25.

Evaluation and genome-wide association study of resistance to bacterial blight race 18 in U.S. Upland cotton germplasm.

Bacterial blight (BB), caused by Xanthomonas citripv.malvacearum (Xcm), is a destructive disease to cotton production in many countries. In the U.S., Xcm race 18 is the most virulent and widespread race and can cause serious yield losses. Planting BB-resistant cotton cultivars is the most effective method of controlling this disease. In this study, 335 U.S. Upland cotton accessions were evaluated for resistance to race 18 using artificial inoculations by scratching cotyledons on an individual plant basis in a greenhouse. The analysis of variance detected significant genotypic variation in disease incidence, and 50 accessions were resistant including 38 lines with no symptoms on either cotyledons or true leaves. Many of the resistant lines were developed in the MAR (multi-adversity resistance) breeding program at Texas A&M University, whereas others were developed before race 18 was first reported in the U.S. in 1973, suggesting a broad base of resistance to race 18. A genome-wide association study (GWAS) based on 26,301 single nucleotide polymorphic (SNP) markers detected 11 quantitative trait loci (QTL) anchored by 79 SNPs, including three QTL on each of the three chromosomes A01, A05 and D02, and one QTL on each of D08 and D10. This study has identified a set of obsolete Upland germplasm with resistance to race 18 and specific chromosomal regions delineated by SNPs for resistance. The results will assist in breeding cotton for BB resistance and facilitate furthergenomic studies in fine mapping resistance genes to enhance the understanding of the genetic basis of BB resistance in cotton.

Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations.

The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.

Genome-wide association study of resistance to PstS2 and Warrior races of Puccinia striiformis f. sp. tritici (stripe rust) in bread wheat landraces.

Stripe or yellow rust, caused by Puccinia striiformis Westend. f. sp. tritici is a major threat to bread wheat production worldwide. The breakdown in resistance of certain major genes and newly emerging aggressive races of stripe rusts pose serious concerns in all main wheat growing areas of the world. To identify new sources of resistance and associated QTL for effective utilization in future breeding programs an association mapping (AM) panel comprising of 600 bread wheat landraces collected from eight different countries conserved at ICARDA gene bank were evaluated for seedling and adult plant resistance against the PstS2 and Warrior races of stripe rust at the Regional Cereal Rust Research Center (RCRRC), Izmir, Turkey during 2016, 2018 and 2019. A set of 25,169 informative SNP markers covering the whole genome were used to examine the population structure, linkage disequilibrium and marker-trait associations in the AM panel. The genome-wide association study (GWAS) was carried out using a Mixed Linear Model (MLM). We identified 47 SNP markers across 19 chromosomes with significant SNP-trait associations for both seedling stage and adult plant resistance. The threshold of significance for all SNP-trait associations was determined by the false discovery rate (q) ≤ 0.05. Three genomic regions (QYr.1D_APR, QYr.3A_seedling and QYr.7D_seedling) identified in this study do not correspond to previously reported Yr genes or QTL, suggesting new genomic regions for stripe rust resistance.

Genome-wide association studies for resistance to viral nervous necrosis in three populations of European sea bass (Dicentrarchus labrax) using a novel 57k SNP array DlabChip

Viral Nervous Necrosis (VNN) is a major threat for the European sea bass (Dicentrarchus labrax) aquaculture industry. The improvement of disease resistance through selective breeding is a promising option to reduce outbreaks. With the development of high-throughput genotyping technologies, identification of genomic regions involved in the resistance could improve the efficiency of selective breeding. The aim of this study was to identify quantitative trait loci (QTL) involved in VNN resistance and to quantify their effect.Four experimental backcross families comprising 378, 454, 291 and 211 individuals and two commercial populations A and B comprising 1027 and 1042 individuals obtained from partial factorial crosses (59♂ x 20♀ for pop A; 39♂ x 14♀ for pop B) were submitted to a redspotted grouper nervous necrosis virus (RGNNV) challenge by bath. A high-density single nucleotide polymorphism (SNP) chip panel was designed to develop the ThermoFisher Axiom™ 57k SNP DlabChip, which was used for genotyping all individuals and building a high quality linkage map. In the backcross families, composite interval mapping was performed on 30,917, 23,592, 30,656 and 31,490 markers, respectively. In the commercial populations, 40,263 markers in pop A and 41,166 markers in pop B were used to perform genome-wide association studies (GWAS) using a GBLUP and a BayesCπ approach.One QTL was identified on chromosome LG12 in three of the four experimental backcross families, and one additional QTL on LG8 was detected in only one family. In commercial populations, QTL mapping revealed a total of seven QTLs, among which the previously mentioned QTL on LG12 was detected in both. This QTL, which was mapped to an interval of 3.45 cM, explained 9.21% of the total genetic variance in pop A, while other identified QTLs individually explained less than 1% of the total genetic variance.The identification of QTL regions involved in VNN resistance in European sea bass, with one having a strong effect, should have a great impact on the aquaculture industry. Future work could focus on the fine mapping of the causal mutation present on LG12 using whole genome sequencing.

Genome-Wide Association Study of Resistance to Potato Common Scab

Potato common scab caused by bacterial pathogen Streptomyces scabies (Thaxt.) Waksman & Henrici is one of the most important diseases of potato (Solanum tuberosum L.) worldwide. Currently, the most effective and desirable method to control common scab is through the use of resistant cultivars. In order to decipher the genetic control of resistance to common scab disease in Canadian potato germplasm, an association panel of 143 clones including advanced breeding clones and commercial cultivars was genotyped with 12K SolCAP SNPs and phenotyped for potato common scab resistances in multiple years. By conducting a genome-wide association analysis (GWAS) using GWASpoly R package, three resistance QTLs were identified on potato chromosomes 2, 4, and 12, respectively. The phenotypic variation explained by these QTLs was 21%, 19%, and 26%, respectively. The QTL on chromosome 2 was simplex-dominant whereas duplex-dominant QTLs were identified on chromosomes 4 and 12. These findings will be useful to design marker-assisted selection and breeding strategies to improve resistance to common scab in new potato cultivars.

A genome-wide association study of resistance to Pseudomonas plecoglossicida infection in the large yellow croaker (Larimichthys crocea)

Cultured large yellow croaker (Larimichthys crocea) is frequently infected by bacteria, thus developing small white granulomas in the spleen and kidneys with high mortality in a few days. We performed a genome-wide association study (GWAS) on the trait of resistance to Pseudomonas plecoglossicida infection in a large yellow croaker population in 222 extreme-phenotype samplings using the whole-genome resequencing technology. With the 254,110 detected SNPs for the trait, three candidate regions associated with disease resistance were found on chromosomes 3, 5 and 20. By combing our GWAS results with the biological functional analysis of immunity genes, we found that IL10, THBS1, IGSF21, IGR and IGH as well as IRF8, TRAIL, CC, TNF and LINGO1 are candidate genes of the disease resistance trait in the large yellow croaker. Moreover, after comparison with transcriptome sequencing data, we found that the candidate genes from GWAS were actually up-regulated or down-regulated. This is the first time that a GWAS combined with a transcriptome-wide study was performed on disease resistance to detect candidate loci and find potential functionally relevant genes in the large yellow croaker.

Genome-wide association study of resistance to stripe rust (Puccinia striiformis f. sp. tritici) in Sichuan wheat

BackgroundStripe rust (also called yellow rust) is a common and serious fungal disease of wheat (Triticum aestivum L.) caused by Puccinia striiformis f. sp. tritici. The narrow genetic basis of modern wheat cultivars and rapid evolution of the rust pathogen have been responsible for periodic and devastating epidemics of wheat rust diseases. In this study, we conducted a genome-wide association study with 44,059 single nucleotide polymorphism markers to identify loci associated with resistance to stripe rust in 244 Sichuan wheat accessions, including 79 landraces and 165 cultivars, in six environments.ResultsIn all the field assessments, 24 accessions displayed stable high resistance to stripe rust. Significant correlations among environments were observed for both infection (IT) and disease severity (DS), and high heritability levels were found for both IT and DS. Using mixed linear models, 12 quantitative trait loci (QTLs) significantly associated with IT and/or DS were identified. Two QTLs were mapped on chromosomes 5AS and 5AL and were distant from previously identified stripe rust resistance genes or QTL regions, indicating that they may be novel resistance loci.ConclusionsOur results revealed that resistance alleles to stripe rust were accumulated in Sichuan wheat germplasm, implying direct or indirect selection for improved stripe rust resistance in elite wheat breeding programs. The identified stable QTLs or favorable alleles could be important chromosome regions in Sichuan wheat that controlled the resistance to stripe rust. These markers can be used molecular marker-assisted breeding of Sichuan wheat cultivars, and will be useful in the ongoing effort to develop new wheat cultivars with strong resistance to stripe rust.

Genome-wide association mapping of genetic factors controlling Septoria tritici blotch resistance and their associations with plant height and heading date in wheat

Septoria tritici blotch (STB), caused by the ascomycete fungus Zymoseptoria tritici (also known as Mycosphaerella graminicola), is one of the most devastating foliar wheat diseases worldwide. Host resistance is the most effective strategy for management of the disease. A factor that complicates the determination of resistance is its reported interaction with heading date (Hd) and plant height (Ph). In this study, we report findings from a genome-wide association study of resistance to STB in a world-wide collection of 96 wheat accessions. The collection was evaluated under conditions of artificial infection for seedling and adult plant STB resistance, Hd and Ph in field trials. Marker-trait associations (MTAs) were detected using a mixed linear model. STB disease severities showed significant phenotypic variation. In total, 73 MTAs involving STB resistance were detected. The chromosomal locations of some of them were similar to known Stb genes or quantitative trait loci; whereas others were detected in new genomic regions. The field experiment showed evidence of genetic association between STB resistance and Hd, but only for a few genotypes. This was corroborated at the molecular level, where a total of eight genomic regions associated with STB resistance were located in similar positions to MTAs for Hd. New genomic regions associated with STB resistance found here could be useful in wheat breeding aimed at controlling STB after validation in relevant genetic backgrounds

A genome-wide association study of resistance to stripe rust (Puccinia striiformis f. sp. tritici) in a worldwide collection of hexaploid spring wheat (Triticum aestivum L.).

New races of Puccinia striiformis f. sp. tritici (Pst), the causal pathogen of wheat stripe rust, show high virulence to previously deployed resistance genes and are responsible for large yield losses worldwide. To identify new sources of resistance we performed a genome-wide association study (GWAS) using a worldwide collection of 1000 spring wheat accessions. Adult plants were evaluated under field conditions in six environments in the western United States, and seedlings were tested with four Pst races. A single-nucleotide polymorphism (SNP) Infinium 9K-assay provided 4585 SNPs suitable for GWAS. High correlations among environments and high heritabilities were observed for stripe rust infection type and severity. Greater levels of Pst resistance were observed in a subpopulation from Southern Asia than in other groups. GWAS identified 97 loci that were significant for at least three environments, including 10 with an experiment-wise adjusted Bonferroni probability < 0.10. These 10 quantitative trait loci (QTL) explained 15% of the phenotypic variation in infection type, a percentage that increased to 45% when all QTL were considered. Three of these 10 QTL were mapped far from previously identified Pst resistance genes and QTL, and likely represent new resistance loci. The other seven QTL mapped close to known resistance genes and allelism tests will be required to test their relationships. In summary, this study provides an integrated view of stripe rust resistance resources in spring wheat and identifies new resistance loci that will be useful to diversify the current set of resistance genes deployed to control this devastating disease.

Genome-wide association study of resistance to rough dwarf disease in maize

Maize rough dwarf disease (MRDD), caused by the Maize rough dwarf virus (MRDV) is highly prevalent across summer at maize-growing areas in China. To investigate the genetic architecture underlying this viral disease, a set of 236 Chinese maize inbred lines was evaluated for resistance to MRDD in 2010 and 2011. Based on 41,101 single-nucleotide polymorphism (SNP) markers with minor allele frequencies (MAF) greater than 5 %, a genome-wide association study (GWAS) was employed to identify genomic loci for resistance to MRDD. A total of 73 SNPs were found to be associated with resistance to MRDD at a significance threshold of -log10 (P) > 4 controlling the false discovery rate (FDR) at α = 0.1. Fourteen of these SNPs were detected in both of the two environments tested. A total of 48 SNPs were identified in linkage disequilibrium (LD) blocks containing candidate resistance genes, including protein kinase genes. Using the pedigree information and whole-genome SNP analysis of five highly resistant inbred lines derived from the hybrid ‘P78599’, nine derivative fragments harbouring SNPs associated with MRDD resistance were detected. One 81.57 Mb fragment in particular located in bin 8.03, which contained six SNPs associated with MRDD resistance, and included the major quantitative trait loci (QTL) that had been identified in the previous study. These results suggest that the SNPs and fragments associated with MRDD resistance, especially those in bin 8.03, could be used for fine mapping of resistance genes and developing resistant varieties in maize.

Genome-Wide Association Analysis of Avian Resistance to Campylobacter jejuni Colonization Identifies Risk Locus Spanning the CDH13 Gene

The enteropathogen Campylobacter jejuni is a major worldwide health and economic burden, being one of the leading causes of bacterial gastroenteritis and commonly linked to postinfectious onset of autoimmune disease. Chickens are a major vector for human infection and even though variation in avian colonization level is heritable, no previous studies have identified regions of the genome associated with colonization resistance. We performed a genome-wide association study of resistance to C. jejuni colonization in the avian intestine by controlling for population structure, which revealed a risk locus with genome-wide significance spanning the T-cadherin (CDH13) gene. A second possible risk locus was also identified close to calmodulin (CALM1), a calcium-activated modulator of cadherin function. In addition, gene expression analysis of mRNA sequencing profiles revealed that the relative expression of the two genes is significantly associated with colonization resistance. Functional studies have previously demonstrated involvement of cadherins and calmodulin in C. jejuni intracellular invasion and colonization of human intestinal epithelial cells in vitro. Consistent with this finding, our analysis reveals that variation surrounding these genes is associated with avian colonization resistance in vivo and highlights their potential as possible targets for control of the bacterium in avian and human populations.

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.