Quantitative Genetics of the Maize Leaf Microbiome

The degree to which the genotype of an organism can affect the composition of its associated microbial communities (“microbiome”) varies by organism and habitat, and in many cases is unknown. We analyzed the metabolically active bacteria of maize leaves across 300 diverse maize lines growing in a common environment. We performed comprehensive heritability analysis for 49 community diversity metrics, 380 bacterial clades, and 9,042 predicted metagenomic functions. We find that only a few bacterial clades (5) and diversity metrics (2) are significantly heritable, while a much larger number of metabolic functions (200) are. Many of these associations appear to be driven by the Methylobacteria in each sample. Among these heritable metabolic traits, Fisher’s exact test identifies significant overrepresentation of traits relating to short-chain carbon metabolism, secretion, and nitrotoluene degradation. Genome-wide association analysis identified a small number of associated loci for these heritable traits, including two that affect multiple traits. Our results indicate that while most of the maize leaf microbiome composition is driven by environmental factors and/or stochastic founder events, a subset of bacterial taxa and metabolic functions is nonetheless significantly impacted by host genetics. Additional work will be needed to identify the exact nature of these interactions and what effects they may have on their host. [Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Download Full-text

Quantitative Genetic Analysis of the Maize Leaf Microbiome

10.1101/268532 ◽

2018 ◽

Cited By ~ 2

Author(s):

Jason G. Wallace ◽

Karl A. Kremling ◽

Edward S. Buckler

Keyword(s):

Community Diversity ◽

Exact Nature ◽

Common Environment ◽

Operational Taxonomic Units ◽

Metabolic Functions ◽

Genome Wide ◽

Significant Enrichment ◽

Heritability Analysis ◽

Founder Events ◽

Diversity Metrics

AbstractThe degree to which an organism can affect its associated microbial communities (“microbiome”) varies by organism and habitat, and in many cases is unknown. We address this question by analyzing the metabolically active bacteria of the maize phyllosphere across 300 diverse maize lines growing in a common environment. We performed comprehensive heritability analysis for 49 community diversity metrics, 380 bacterial clades (individual operational taxonomic units and higher-level groupings), and 9042 predicted metagenomic functions. We find that only a few few bacterial clades (5) and diversity metrics (2) are significantly heritable, while a much larger number of metabolic functions (200) are. Many of these associations appear to be driven by the amount of Methylobacteria present in each sample, and we find significant enrichment for traits relating to short-chain carbon metabolism, secretion, and nitrotoluene degradation. Genome-wide association analysis identifies a small number of associated loci for these heritable traits, including two loci (on maize chromosomes 7 and 10) that affect a large number of traits even after correcting for correlations among traits. This work is among the most comprehensive analyses of the maize phyllosphere to date. Our results indicate that while most of the maize phyllosphere composition is driven by environmental factors and/or stochastic founder events, a subset of bacterial taxa and metabolic functions is nonetheless significantly impacted by host plant genetics. Additional work will be needed to identify the exact nature of these interactions and what effects they may have on the phenotype of host plants.

Download Full-text

Community diversity metrics, interactions, and metabolic functions of bacteria associated with municipal solid waste landfills at different maturation stages

MicrobiologyOpen ◽

10.1002/mbo3.1118 ◽

2020 ◽

Author(s):

Lerato Sekhohola‐Dlamini ◽

Ramganesh Selvarajan ◽

Henry Joseph Odour Ogola ◽

Memory Tekere

Keyword(s):

Municipal Solid Waste ◽

Solid Waste ◽

Community Diversity ◽

Metabolic Functions ◽

Maturation Stages ◽

Municipal Solid Waste Landfills ◽

Solid Waste Landfills ◽

Diversity Metrics

Download Full-text

Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations

Nature Communications ◽

10.1038/s41467-021-21001-0 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Ruidong Xiang ◽

Iona M. MacLeod ◽

Hans D. Daetwyler ◽

Gerben de Jong ◽

Erin O’Connor ◽

...

Keyword(s):

Dairy Cattle ◽

Chromosome Segment ◽

Multiple Traits ◽

Functional Variants ◽

Genome Wide ◽

The Usa ◽

Pleiotropic Qtl ◽

Causal Variants ◽

Genetic Value ◽

Bayesian Mixture Models

AbstractThe difficulty in finding causative mutations has hampered their use in genomic prediction. Here, we present a methodology to fine-map potentially causal variants genome-wide by integrating the functional, evolutionary and pleiotropic information of variants using GWAS, variant clustering and Bayesian mixture models. Our analysis of 17 million sequence variants in 44,000+ Australian dairy cattle for 34 traits suggests, on average, one pleiotropic QTL existing in each 50 kb chromosome-segment. We selected a set of 80k variants representing potentially causal variants within each chromosome segment to develop a bovine XT-50K genotyping array. The custom array contains many pleiotropic variants with biological functions, including splicing QTLs and variants at conserved sites across 100 vertebrate species. This biology-informed custom array outperformed the standard array in predicting genetic value of multiple traits across populations in independent datasets of 90,000+ dairy cattle from the USA, Australia and New Zealand.

Download Full-text

Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations

Blood ◽

10.1182/blood-2011-12-399683 ◽

2012 ◽

Vol 120 (10) ◽

pp. 2076-2086 ◽

Cited By ~ 113

Author(s):

Britta Will ◽

Li Zhou ◽

Thomas O. Vogler ◽

Susanna Ben-Neriah ◽

Carolina Schinke ◽

...

Keyword(s):

Progenitor Cells ◽

Genetic Alterations ◽

Fish Analysis ◽

Exact Nature ◽

Clinical Relapse ◽

Hematopoietic Stem ◽

Molecular Alterations ◽

Genome Wide ◽

Stem And Progenitor Cells ◽

Specific Expansion

Abstract Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage−/CD34+/CD38−/CD90+) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations.

Download Full-text

Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women

mSystems ◽

10.1128/msystems.00502-20 ◽

2020 ◽

Vol 5 (4) ◽

Cited By ~ 2

Author(s):

Supriya D. Mehta ◽

Drew R. Nannini ◽

Fredrick Otieno ◽

Stefan J. Green ◽

Walter Agingu ◽

...

Keyword(s):

Racial Differences ◽

Genome Wide Association Study ◽

Vaginal Microbiome ◽

Content Type ◽

Microbiome Composition ◽

Genome Wide ◽

A Genome ◽

Kenyan Women ◽

Host Genetic ◽

Women Of African Descent

ABSTRACT Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Persistent racial differences in BV and diverse vaginal microbiome composition overlap with racial disparities in risks for HIV and sexually transmitted infection, especially among women of African descent. Risk factors for BV and nonoptimal vaginal microbiome include sexual practices, yet racial differences persist when adjusted for behavioral factors, suggesting a host genetic component. Here, we perform a genome-wide association study on vaginal microbiome traits in Kenyan women. Linear regression and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, Shannon diversity index, and community state type (CST) with host genetic single nucleotide polymorphisms (SNPs). We identified novel genomic loci associated with the vaginal microbiome traits, though no SNP reached genome-wide significance. During pathway enrichment analysis, Toll-like receptors (TLRs), cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple previously reported genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP (L. iners, Shannon), TLR2 (Shannon, CST), MBL2 (L. iners, G. vaginalis, CST), and MYD88 (L. iners, Shannon). These genetic associations suggest a role for the innate immune system and cell signaling in vaginal microbiome composition and susceptibility to nonoptimal vaginal microbiome. IMPORTANCE Globally, bacterial vaginosis (BV) is a common condition in women. BV is associated with poorer reproductive health outcomes and HIV risk. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Despite many women having similar exposures, the prevalence of BV and nonoptimal vaginal microbiome is increased for women of African descent, suggesting a possible role for host genetics. We conducted a genome-wide association study of important vaginal microbiome traits in Kenyan women. We identified novel genetic loci and biological pathways related to mucosal immunity, cell signaling, and infection that were associated with vaginal microbiome traits; we replicated previously reported loci associated with mucosal immune response. These results provide insight into potential host genetic influences on vaginal microbiome composition and can guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals and across populations.

Download Full-text

Genetic Basis of Maize Resistance to Multiple Insect Pests: Integrated Genome-Wide Comparative Mapping and Candidate Gene Prioritization

Genes ◽

10.3390/genes11060689 ◽

2020 ◽

Vol 11 (6) ◽

pp. 689

Author(s):

A. Badji ◽

D. B. Kwemoi ◽

L. Machida ◽

D. Okii ◽

N. Mwila ◽

...

Keyword(s):

Insect Resistance ◽

Defense Mechanisms ◽

Genome Wide Association Study ◽

Insect Pests ◽

Physical Map ◽

Fall Armyworm ◽

Nucleotide Polymorphisms ◽

Multiple Traits ◽

Maize Weevil ◽

Genome Wide

Several species of herbivores feed on maize in field and storage setups, making the development of multiple insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to fall armyworm (FAW), whilst bulked grains were subjected to a maize weevil (MW) bioassay and genotyped with Diversity Array Technology’s single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance levels of 0.05 and 0.01, respectively, and located within or close to multiple insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple traits, of which, six were associated with resistance to both FAW and MW, suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10–30 kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of the five of the six combined resistance QTNs, thus reinforcing the pleiotropy hypothesis. In addition, through in silico co-functional network inferences, an additional 107 network-based CGs (NbCGs), biologically connected to the 64 GbCGs, and differentially expressed under biotic or abiotic stress, were revealed within MIRGRs. The provided multiple insect resistance physical map should contribute to the development of combined insect resistance in maize.

Download Full-text

Genome-Wide Association Study for Maize Leaf Cuticular Conductance Identifies Candidate Genes Involved in the Regulation of Cuticle Development

G3 Genes|Genome|Genetics ◽

10.1534/g3.119.400884 ◽

2020 ◽

Vol 10 (5) ◽

pp. 1671-1683 ◽

Cited By ~ 2

Author(s):

Meng Lin ◽

Susanne Matschi ◽

Miguel Vasquez ◽

James Chamness ◽

Nicholas Kaczmar ◽

...

Keyword(s):

Association Study ◽

Candidate Genes ◽

Genome Wide Association Study ◽

Crop Productivity ◽

Genome Wide Association ◽

Cell Wall Modification ◽

Major Barrier ◽

Maize Leaf ◽

Genome Wide ◽

A Genome

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of gc of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with gc were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and β-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of gc in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of gc and have the potential to help breeders more effectively develop drought-tolerant maize for target environments.

Download Full-text

P708Identification of 26 novel loci that confer susceptibility to early-onset coronary artery disease in a Japanese population

European Heart Journal ◽

10.1093/eurheartj/ehz747.0313 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Oguri ◽

K Kato ◽

H Horibe ◽

T Fujimaki ◽

J Sakuma ◽

...

Keyword(s):

Coronary Artery Disease ◽

Genetic Variants ◽

Early Onset ◽

Association Studies ◽

Allele Frequencies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Exact Test ◽

Genome Wide ◽

Artery Disease

Abstract Background Early-onset coronary artery disease (CAD) has a strong genetic component. Although genome-wide association studies have identified various genes and loci significantly associated with CAD mainly in European ancestry populations, genetic variants that contribute to susceptibility to this condition in Japanese individuals remain to be identified definitively. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to early-onset CAD in Japanese. We have now performed exome-wide association studies (EWASs) in subjects with early-onset CAD and controls. Methods A total of 7256 individuals aged ≤65 years was enrolled in the study. The EWAS was conducted with 1482 subjects with CAD and 5774 controls. Genotyping of single nucleotide polymorphisms (SNPs) was performed with Illumina Human Exome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 31,465 SNPs that passed quality control to CAD was examined with Fisher's exact test. To compensate for multiple comparisons of allele frequencies with CAD, we applied a false discovery rate (FDR) of <0.05 for statistical significance of association. Results The relation of allele frequencies for 31,465 SNPs to CAD with the use of Fisher's exact test showed that 170 SNPs were significantly (FDR <0.05) associated with CAD. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension, diabetes mellitus, and dyslipidemia revealed that 162 SNPs were significantly (P<0.05) related to CAD. A stepwise forward selection procedure was performed to examine the effects of genotypes for the 162 SNPs on CAD. The 54 SNPs were significant (P<0.05) and independent [coefficient of determination (R2), 0.0008 to 0.0297] determinants of CAD. These SNPs together accounted for 15.5% of the cause of CAD. After examination of results from previous genome-wide association studies and linkage disequilibrium of the identified SNPs, we newly identified 21 genes (RNF2, YEATS2, USP45, ITGB8, TNS3, FAM170B-AS1, PRKG1, BTRC, MKI67, STIM1, OR52E4, KIAA1551, MON2, PLUT, LINC00354, TRPM1, ADAT1, KRT27, LIPE, GFY, EIF3L) and five chromosomal regions (2p13, 4q31.2, 5q12, 13q34, 20q13.2) that were significantly associated with CAD. Gene ontology analysis showed that various biological functions were predicted in the 18 genes identified in the present study. The network analysis revealed that the 18 genes had potential direct or indirect interactions with the 30 genes previously shown to be associated with CAD or with the 228 genes identified in previous genome-wide association studies of CAD. Conclusion We have newly identified 26 loci that confer susceptibility to CAD. Determination of genotypes for the SNPs at these loci may prove informative for assessment of the genetic risk for CAD in Japanese.

Download Full-text