scholarly journals A Truncated Singleton NLR Causes Hybrid Necrosis in Arabidopsis thaliana

2020 ◽  
Author(s):  
Ana Cristina Barragan ◽  
Maximilian Collenberg ◽  
Jinge Wang ◽  
Rachelle R Q Lee ◽  
Wei Yuan Cher ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Risk Allele ◽  
Genomic Region ◽  
Risk Haplotype ◽  
Leucine Rich Repeat ◽  
Hybrid Necrosis ◽  
Incompatible Interaction ◽  
Risk Alleles ◽  
Immunity Genes ◽  
Transcriptional Changes

Abstract Hybrid necrosis in plants arises from conflict between divergent alleles of immunity genes contributed by different parents, resulting in autoimmunity. We investigate a severe hybrid necrosis case in Arabidopsis thaliana, where the hybrid does not develop past the cotyledon stage and dies 3 weeks after sowing. Massive transcriptional changes take place in the hybrid, including the upregulation of most NLR (nucleotide-binding site leucine-rich repeat) disease-resistance genes. This is due to an incompatible interaction between the singleton TIR-NLR gene DANGEROUS MIX 10 (DM10), which was recently relocated from a larger NLR cluster, and an unlinked locus, DANGEROUS MIX 11 (DM11). There are multiple DM10 allelic variants in the global A. thaliana population, several of which have premature stop codons. One of these, which has a truncated LRR–PL (leucine-rich repeat [LRR]–post-LRR) region, corresponds to the DM10 risk allele. The DM10 locus and the adjacent genomic region in the risk allele carriers are highly differentiated from those in the nonrisk carriers in the global A. thaliana population, suggesting that this allele became geographically widespread only relatively recently. The DM11 risk allele is much rarer and found only in two accessions from southwestern Spain—a region from which the DM10 risk haplotype is absent—indicating that the ranges of DM10 and DM11 risk alleles may be nonoverlapping.

scholarly journals A singleton NLR of recent origin causes hybrid necrosis in Arabidopsis thaliana

2020 ◽  
Author(s):  
A. Cristina Barragan ◽  
Maximilian Collenberg ◽  
Jinge Wang ◽  
Rachelle R.Q. Lee ◽  
Wei Yuan Cher ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Risk Allele ◽  
Genomic Region ◽  
Risk Haplotype ◽  
Hybrid Necrosis ◽  
Risk Alleles ◽  
Immunity Genes ◽  
Transcriptional Changes ◽  
Recent Origin ◽  
Lrr Domain

AbstractHybrid necrosis in plants arises from conflict between divergent alleles of immunity genes contributed by different parents, resulting in autoimmunity. We investigate a severe hybrid necrosis case in Arabidopsis thaliana, where the hybrid does not develop past the cotyledon stage and dies three weeks after sowing. Massive transcriptional changes take place in the hybrid, including the upregulation of most NLR disease resistance genes. This is due to an incompatible interaction between the singleton TIR-NLR gene DANGEROUS MIX 10 (DM10), which was recently relocated from a larger NLR cluster, and an unlinked locus, DANGEROUS MIX 11 (DM11). There are multiple DM10 allelic variants in the global A. thaliana population, several of which have premature stop codons. One of these, which has a truncated LRR domain, corresponds to the DM10 risk allele. The DM10 locus and the adjacent genomic region in the risk allele carriers are highly differentiated from those in the non-risk carriers in the global A. thaliana population, suggesting that this allele became geographically widespread only relatively recently. The DM11 risk allele is much rarer and found only in two accessions from southwestern Spain – a region from which the DM10 risk haplotype is absent – indicating that the ranges of DM10 and DM11 risk alleles may be non-overlapping.

scholarly journals Recombination and Gene Conversion in a 170-kb Genomic Region of Arabidopsis thaliana

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1269-1278 ◽  
Author(s):  
Bernhard Haubold ◽  
Jürgen Kroymann ◽  
Andreas Ratzka ◽  
Thomas Mitchell-Olds ◽  
Thomas Wiehe
Keyword(s):  
Genetic Diversity ◽  
Arabidopsis Thaliana ◽  
Linkage Disequilibrium ◽  
Gene Conversion ◽  
Genomic Sequence ◽  
Genomic Region ◽  
Resistance To Herbivory ◽  
Linkage Disequilibria ◽  
Coalescent Simulations ◽  
The Mean

Abstract Arabidopsis thaliana is a highly selfing plant that nevertheless appears to undergo substantial recombination. To reconcile its selfing habit with the observations of recombination, we have sampled the genetic diversity of A. thaliana at 14 loci of ~500 bp each, spread across 170 kb of genomic sequence centered on a QTL for resistance to herbivory. A total of 170 of the 6321 nucleotides surveyed were polymorphic, with 169 being biallelic. The mean silent genetic diversity (πs) varied between 0.001 and 0.03. Pairwise linkage disequilibria between the polymorphisms were negatively correlated with distance, although this effect vanished when only pairs of polymorphisms with four haplotypes were included in the analysis. The absence of a consistent negative correlation between distance and linkage disequilibrium indicated that gene conversion might have played an important role in distributing genetic diversity throughout the region. We tested this by coalescent simulations and estimate that up to 90% of recombination is due to gene conversion.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis

2021 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

scholarly journals Transcriptional Changes of the Root-Knot Nematode Meloidogyne incognita in Response to Arabidopsis thaliana Root Signals

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61259 ◽  
Author(s):  
Alice Teillet ◽  
Katarzyna Dybal ◽  
Brian R. Kerry ◽  
Anthony J. Miller ◽  
Rosane H. C. Curtis ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Meloidogyne Incognita ◽  
Root Knot Nematode ◽  
Root Signals ◽  
Transcriptional Changes

scholarly journals Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Prithvi Raj ◽  
Ran Song ◽  
Honglin Zhu ◽  
Linley Riediger ◽  
Dong-Jae Jun ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Deep Sequencing ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Risk Allele ◽  
Snp Array ◽  
Low Frequency ◽  
Risk Haplotype ◽  
Systemic Lupus ◽  
Altered Expression

Abstract Background Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease characterized by the development of anti-nuclear antibodies. Susceptibility to SLE is multifactorial, with a combination of genetic and environmental risk factors contributing to disease development. Like other polygenic diseases, a significant proportion of estimated SLE heritability is not accounted for by common disease alleles analyzed by SNP array-based GWASs. Death-associated protein 1 (DAP1) was implicated as a candidate gene in a previous familial linkage study of SLE and rheumatoid arthritis, but the association has not been explored further. Results We perform deep sequencing across the DAP1 genomic segment in 2032 SLE patients, and healthy controls, and discover a low-frequency functional haplotype strongly associated with SLE risk in multiple ethnicities. We find multiple cis-eQTLs embedded in a risk haplotype that progressively downregulates DAP1 transcription in immune cells. Decreased DAP1 transcription results in reduced DAP1 protein in peripheral blood mononuclear cells, monocytes, and lymphoblastoid cell lines, leading to enhanced autophagic flux in immune cells expressing the DAP1 risk haplotype. Patients with DAP1 risk allele exhibit significantly higher autoantibody titers and altered expression of the immune system, autophagy, and apoptosis pathway transcripts, indicating that the DAP1 risk allele mediates enhanced autophagy, leading to the survival of autoreactive lymphocytes and increased autoantibody. Conclusions We demonstrate how targeted sequencing captures low-frequency functional risk alleles that are missed by SNP array-based studies. SLE patients with the DAP1 genotype have distinct autoantibody and transcription profiles, supporting the dissection of SLE heterogeneity by genetic analysis.

scholarly journals Trans-Ancestral Fine-Mapping and Epigenetic Annotation as Tools to Delineate Functionally Relevant Risk Alleles at IKZF1 and IKZF3 in Systemic Lupus Erythematosus

2020 ◽  
Vol 21 (21) ◽  
pp. 8383
Author(s):  
Timothy J. Vyse ◽  
Deborah S. Cunninghame Graham
Keyword(s):  
Binding Sites ◽  
Dnase I ◽  
Common Disease ◽  
Risk Haplotype ◽  
Dnase I Hypersensitivity ◽  
Biological Relevance ◽  
Tag Snps ◽  
Risk Alleles ◽  
Allele Specific ◽  
Exclusion Mapping

Background: Prioritizing tag-SNPs carried on extended risk haplotypes at susceptibility loci for common disease is a challenge. Methods: We utilized trans-ancestral exclusion mapping to reduce risk haplotypes at IKZF1 and IKZF3 identified in multiple ancestries from SLE GWAS and ImmunoChip datasets. We characterized functional annotation data across each risk haplotype from publicly available datasets including ENCODE, RoadMap Consortium, PC Hi-C data from 3D genome browser, NESDR NTR conditional eQTL database, GeneCards Genehancers and TF (transcription factor) binding sites from Haploregv4. Results: We refined the 60 kb associated haplotype upstream of IKZF1 to just 12 tag-SNPs tagging a 47.7 kb core risk haplotype. There was preferential enrichment of DNAse I hypersensitivity and H3K27ac modification across the 3′ end of the risk haplotype, with four tag-SNPs sharing allele-specific TF binding sites with promoter variants, which are eQTLs for IKZF1 in whole blood. At IKZF3, we refined a core risk haplotype of 101 kb (27 tag-SNPs) from an initial extended haplotype of 194 kb (282 tag-SNPs), which had widespread DNAse I hypersensitivity, H3K27ac modification and multiple allele-specific TF binding sites. Dimerization of Fox family TFs bound at the 3′ and promoter of IKZF3 may stabilize chromatin looping across the locus. Conclusions: We combined trans-ancestral exclusion mapping and epigenetic annotation to identify variants at both IKZF1 and IKZF3 with the highest likelihood of biological relevance. The approach will be of strong interest to other complex trait geneticists seeking to attribute biological relevance to risk alleles on extended risk haplotypes in their disease of interest.

scholarly journals GNB3 and FTO Polymorphisms and Pregnancy Weight Gain in Black Women

2014 ◽  
Vol 17 (4) ◽  
pp. 405-412 ◽  
Author(s):  
Susan W. Groth ◽  
Dianne Morrison-Beedy
Keyword(s):  
Weight Gain ◽  
Black Women ◽  
Body Mass ◽  
Low Income ◽  
Risk Allele ◽  
Obese Women ◽  
Fto Gene ◽  
Prepregnancy Bmi ◽  
Risk Alleles ◽  
Infant Birth

Background: Gestational weight gain (GWG) is a modifiable risk factor for obesity in women. Black women have the greatest prevalence of high body mass, which predisposes them to excessive GWG. Increased understanding of genetic influences on GWG has implications for the health of women. The purpose of this study was to explore the associations of GNB3 and FTO risk alleles in pregnant women with prepregnancy body mass index (BMI), GWG, and postpartum and infant birth weights. Research design and Methods: This was an observational, prospective candidate gene association study. Pregnant, low-income Black women ( N = 97) were enrolled in early pregnancy and followed until 6 months postpartum. Results: GWG differed depending on number of FTO risk alleles. The mean 6-month postpartum BMI differed, although not significantly, by 4 kg/m2 between homozygous women. There was an interaction between the FTO risk allele and prepregnancy BMI ( p = .022), with obese homozygote AA women having significantly higher mean GWG than obese TT women. When controlling for age and smoking, the FTO gene and physical activity predicted GWG ( p = .032). Although not statistically significant, women who carried the GNB3 T risk allele gained 6 pounds more than noncarriers, and mean 6-month postpartum BMI differed by 2.2 kg/m2 between homozygous women. Neither the GNB3 nor FTO gene predicted prepregnancy BMI, infant birth weight, or postpartum weight. Conclusion: Obese women homozygous for the FTO risk allele were at greater risk of excessive GWG compared to nonrisk allele homozygous obese women or nonobese women. This study provides evidence of the FTO gene’s effect on GWG in Black women.

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