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1.
BMC Genomics ; 22(1): 636, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34474664

RESUMO

BACKGROUND: Association mapping studies of quantitative trait loci (QTL) for canine hip dysplasia (CHD) can contribute to the understanding of the genetic background of this common and debilitating disease and might contribute to its genetic improvement. The power of association studies for CHD is limited by relatively small sample numbers for CHD records within countries, suggesting potential benefits of joining data across countries. However, this is complicated due to the use of different scoring systems across countries. In this study, we incorporated routinely assessed CHD records and genotype data of German Shepherd dogs from two countries (UK and Sweden) to perform genome-wide association studies (GWAS) within populations using different variations of CHD phenotypes. As phenotypes, dogs were either classified into cases and controls based on the Fédération Cynologique Internationale (FCI) five-level grading of the worst hip or the FCI grade was treated as an ordinal trait. In a subsequent meta-analysis, we added publicly available data from a Finnish population and performed the GWAS across all populations. Genetic associations for the CHD phenotypes were evaluated in a linear mixed model using 62,089 SNPs. RESULTS: Multiple SNPs with genome-wide significant and suggestive associations were detected in single-population GWAS and the meta-analysis. Few of these SNPs overlapped between populations or between single-population GWAS and the meta-analysis, suggesting that many CHD-related QTL are population-specific. More significant or suggestive SNPs were identified when FCI grades were used as phenotypes in comparison to the case-control approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional candidate genes associated with hip dysplasia. CONCLUSIONS: Our findings confirm the complex genetic nature of hip dysplasia in dogs, with multiple loci associated with the trait, most of which are population-specific. Routinely assessed CHD information collected across countries provide an opportunity to increase sample sizes and statistical power for association studies. While the lack of standardisation of CHD assessment schemes across countries poses a challenge, we showed that conversion of traits can be utilised to overcome this obstacle.


Assuntos
Displasia Pélvica Canina , Animais , Cães , Estudo de Associação Genômica Ampla , Genótipo , Displasia Pélvica Canina/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
2.
BMC Plant Biol ; 21(1): 417, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507551

RESUMO

BACKGROUND: The future productivity of wheat (T. aestivum L.) as the most grown crop worldwide is of utmost importance for global food security. Thousand kernel weight (TKW) in wheat is closely associated with grain architecture-related traits, e.g. kernel length (KL), kernel width (KW), kernel area (KA), kernel diameter ratio (KDR), and factor form density (FFD). Discovering the genetic architecture of natural variation in these traits, identifying QTL and candidate genes are the main aims of this study. Therefore, grain architecture-related traits in 261 worldwide winter accessions over three field-year experiments were evaluated. RESULTS: Genome-wide association analysis using 90K SNP array in FarmCPU model revealed several interesting genomic regions including 17 significant SNPs passing false discovery rate threshold and strongly associated with the studied traits. Four of associated SNPs were physically located inside candidate genes within LD interval e.g. BobWhite_c5872_589 (602,710,399 bp) found to be inside TraesCS6A01G383800 (602,699,767-602,711,726 bp). Further analysis reveals the four novel candidate genes potentially involved in more than one grain architecture-related traits with a pleiotropic effects e.g. TraesCS6A01G383800 gene on 6A encoding oxidoreductase activity was associated with TKW and KA. The allelic variation at the associated SNPs showed significant differences betweeen the accessions carying the wild and mutated alleles e.g. accessions carying C allele of BobWhite_c5872_589, TraesCS6A01G383800 had significantly higher TKW than the accessions carying T allele. Interestingly, these genes were highly expressed in the grain-tissues, demonstrating their pivotal role in controlling the grain architecture. CONCLUSIONS: These results are valuable for identifying regions associated with kernel weight and dimensions and potentially help breeders in improving kernel weight and architecture-related traits in order to increase wheat yield potential and end-use quality.


Assuntos
Genótipo , Fenótipo , Polimorfismo de Nucleotídeo Único , Sementes/anatomia & histologia , Sementes/genética , Triticum/anatomia & histologia , Triticum/genética , Grão Comestível/anatomia & histologia , Grão Comestível/genética , Variação Genética , Genoma de Planta , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas
3.
Nat Commun ; 12(1): 5251, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475392

RESUMO

DNA methylation (DNAm) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.


Assuntos
Metilação de DNA , Genoma Humano , Locos de Características Quantitativas/genética , Esquizofrenia/genética , Fatores Etários , Encéfalo/metabolismo , Encéfalo/patologia , Ilhas de CpG/genética , Epigênese Genética , Predisposição Genética para Doença/genética , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
4.
Nat Commun ; 12(1): 5242, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475398

RESUMO

Genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs) at >250 loci in the human genome to type 2 diabetes (T2D) risk. For each locus, identifying the functional variant(s) among multiple SNPs in high linkage disequilibrium is critical to understand molecular mechanisms underlying T2D genetic risk. Using massively parallel reporter assays (MPRA), we test the cis-regulatory effects of SNPs associated with T2D and altered in vivo islet chromatin accessibility in MIN6 ß cells under steady state and pathophysiologic endoplasmic reticulum (ER) stress conditions. We identify 1,982/6,621 (29.9%) SNP-containing elements that activate transcription in MIN6 and 879 SNP alleles that modulate MPRA activity. Multiple T2D-associated SNPs alter the activity of short interspersed nuclear element (SINE)-containing elements that are strongly induced by ER stress. We identify 220 functional variants at 104 T2D association signals, narrowing 54 signals to a single candidate SNP. Together, this study identifies elements driving ß cell steady state and ER stress-responsive transcriptional activation, nominates causal T2D SNPs, and uncovers potential roles for repetitive elements in ß cell transcriptional stress response and T2D genetics.


Assuntos
Diabetes Mellitus Tipo 2/genética , Estresse do Retículo Endoplasmático/genética , Células Secretoras de Insulina/patologia , Polimorfismo de Nucleotídeo Único , Ativação Transcricional/genética , Alelos , Animais , Linhagem Celular , Cromatina/metabolismo , Diabetes Mellitus Tipo 2/patologia , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Locos de Características Quantitativas , Elementos Nucleotídeos Curtos e Dispersos/genética
5.
BMC Plant Biol ; 21(1): 403, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488630

RESUMO

BACKGROUND: Winter freezing temperature impacts alfalfa (Medicago sativa L.) persistence and seasonal yield and can lead to the death of the plant. Understanding the genetic mechanisms of alfalfa freezing tolerance (FT) using high-throughput phenotyping and genotyping is crucial to select suitable germplasm and develop winter-hardy cultivars. Several clones of an alfalfa F1 mapping population (3010 x CW 1010) were tested for FT using a cold chamber. The population was genotyped with SNP markers identified using genotyping-by-sequencing (GBS) and the quantitative trait loci (QTL) associated with FT were mapped on the parent-specific linkage maps. The ultimate goal is to develop non-dormant and winter-hardy alfalfa cultivars that can produce extended growth in the areas where winters are often mild. RESULTS: Alfalfa FT screening method optimized in this experiment comprises three major steps: clone preparation, acclimation, and freezing test. Twenty clones of each genotype were tested, where 10 samples were treated with freezing temperature, and 10 were used as controls. A moderate positive correlation (r ~ 0.36, P < 0.01) was observed between indoor FT and field-based winter hardiness (WH), suggesting that the indoor FT test is a useful indirect selection method for winter hardiness of alfalfa germplasm. We detected a total of 20 QTL associated with four traits; nine for visual rating-based FT, five for percentage survival (PS), four for treated to control regrowth ratio (RR), and two for treated to control biomass ratio (BR). Some QTL positions overlapped with WH QTL reported previously, suggesting a genetic relationship between FT and WH. Some favorable QTL from the winter-hardy parent (3010) were from the potential genic region for a cold tolerance gene CBF. The BLAST alignment of a CBF sequence of M. truncatula, a close relative of alfalfa, against the alfalfa reference showed that the gene's ortholog resides around 75 Mb on chromosome 6. CONCLUSIONS: The indoor freezing tolerance selection method reported is useful for alfalfa breeders to accelerate breeding cycles through indirect selection. The QTL and associated markers add to the genomic resources for the research community and can be used in marker-assisted selection (MAS) for alfalfa cold tolerance improvement.


Assuntos
Mapeamento Cromossômico , Congelamento , Regulação da Expressão Gênica de Plantas/fisiologia , Medicago sativa/metabolismo , Locos de Características Quantitativas , Adaptação Fisiológica/genética , Cromossomos de Plantas/genética , Genótipo , Medicago sativa/genética , Fenótipo , Melhoramento Vegetal
6.
BMC Plant Biol ; 21(1): 418, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517837

RESUMO

BACKGROUND: Bread wheat (Triticum aestivum L.) is one of the most widely consumed cereal crops, but its complex genome makes it difficult to investigate the genetic effect on important agronomic traits. Genome-wide association (GWA) analysis is a useful method to identify genetic loci controlling complex phenotypic traits. With the RNA-sequencing based gene expression analysis, putative candidate genes governing important agronomic trait can be suggested and also molecular markers can be developed. RESULTS: We observed major quantitative agronomic traits of wheat; the winter survival rate (WSR), days to heading (DTH), days to maturity (DTM), stem length (SL), spike length (SPL), awn length (AL), liter weight (LW), thousand kernel weight (TKW), and the number of seeds per spike (SPS), of 287 wheat accessions from diverse country origins. A significant correlation was observed between the observed traits, and the wheat genotypes were divided into three subpopulations according to the population structure analysis. The best linear unbiased prediction (BLUP) values of the genotypic effect for each trait under different environments were predicted, and these were used for GWA analysis based on a mixed linear model (MLM). A total of 254 highly significant marker-trait associations (MTAs) were identified, and 28 candidate genes closely located to the significant markers were predicted by searching the wheat reference genome and RNAseq data. Further, it was shown that the phenotypic traits were significantly affected by the accumulation of favorable or unfavorable alleles. CONCLUSIONS: From this study, newly identified MTA and putative agronomically useful genes will help to study molecular mechanism of each phenotypic trait. Further, the agronomically favorable alleles found in this study can be used to develop wheats with superior agronomic traits.


Assuntos
Genótipo , Fenótipo , Locos de Características Quantitativas , Sementes/anatomia & histologia , Sementes/genética , Triticum/anatomia & histologia , Triticum/genética , Grão Comestível/anatomia & histologia , Grão Comestível/genética , Variação Genética , Genoma de Planta , Estudo de Associação Genômica Ampla
7.
BMC Genomics ; 22(1): 615, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384356

RESUMO

BACKGROUND: Telmatochromis temporalis is a cichlid fish endemic to Lake Tanganyika. The normal and dwarf morphs of this fish are a clear example of ongoing ecological speciation, and body size plays an important role in this speciation event as a magic trait. However, the genetic basis underlying this trait has not been studied. RESULTS: Based on double-digested restriction-site associated DNA (ddRAD) sequencing of a hybrid cross between the morphs that includes F0 male, F0 female, and 206 F2 individuals, we obtained a linkage map consisting of 708 ddRAD markers in 22 linkage groups, which corresponded to the previously reported Oreochromis niloticus chromosomes, and identified one significant and five suggestive quantitative trait loci (QTL) for body size. From the body-size distribution pattern, the significant and three of the five suggestive QTL are possibly associated with genes responsible for the difference in body size between the morphs. CONCLUSIONS: The QTL analysis presented here suggests that multiple genes, rather than a single gene, control morph-specific body size. The present results provide further insights about the genes underlying the morph specific body size and evolution of the magic trait during ecological speciation.


Assuntos
Ciclídeos , Locos de Características Quantitativas , Animais , Mapeamento Cromossômico , Ciclídeos/genética , Feminino , Ligação Genética , Humanos , Masculino , Fenótipo
8.
Theriogenology ; 173: 156-162, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34392169

RESUMO

The age at first calving has a great economic impact on the beef cattle system and calving at 24 months is an objective of selection for a more efficient herd. However, an age at first calving around 36 months has been observed for Nellore cattle in Brazil. Thus, a genome-wide association study (GWAS) was carried out with 8376 records of age at first calving and 3239 animals genotyped with the GGP-Indicus 35K, which has been developed specifically for Bos taurus indicus. The weighted single-step genomic best linear unbiased prediction method was used, with adjacent SNPs (single nucleotide polymorphisms) in genomic windows of 1.0 Mb. After quality control, 3239 (2161 males and 1078 females) animals genotyped for 30,519 SNPs were used in GWAS analysis. The average and standard deviation of age at first calving were 1041.7 and 140.6 days, respectively. The heritability estimate was 0.10 ± 0.02. The GWAS analysis found seven genomic regions in BTA1, 2, 5, 12, 18, 21, and 24, which explained a total of 11.24% of the additive genetic variance of age at first calving. In these regions were found 62 protein coding genes, and the genes HSD17B2, SERPINA14, SERPINA1, SERPINA5, STAT1, NFATC1, ATP9B, CTDP1, THPO, ECE2, PSMD2, EIF4G1, EIF2B2, DVL3, POLR2H, TMTC2, and GPC6 are possible candidates for age at first birth due their function. Moreover, two molecular functions ("serine-type endopeptidase inhibitor activity" and "negative regulation of endopeptidase activity") were significant, which depend on several serpin genes. The use of a SNP chip developed especially for Bos taurus indicus allowed to find genomic regions for age at first calving, which are close to QTLs previously reported for other reproduction-related traits. Future studies can reveal the causal variants and their effects on reproductive precocity of Nellore cows.


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Feminino , Estudo de Associação Genômica Ampla/veterinária , Genótipo , Masculino , Fenótipo , Locos de Características Quantitativas
9.
Nat Commun ; 12(1): 5071, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417470

RESUMO

Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.


Assuntos
Alcoolismo/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica , Doenças Neurodegenerativas/genética , Encéfalo/metabolismo , Epigênese Genética , Feto/metabolismo , Redes Reguladoras de Genes , Loci Gênicos , Marcadores Genéticos , Humanos , Desequilíbrio de Ligação/genética , Análise da Randomização Mendeliana , Mapeamento Físico do Cromossomo , Regiões Promotoras Genéticas/genética , Locos de Características Quantitativas/genética
10.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360958

RESUMO

Semi-dwarfism is a main agronomic trait in crop breeding. In this study, we performed genome-wide association study (GWAS) and identified a new quantitative trait nucleotide (QTN) for rice shoot length. The peak QTN (C/T) was located in the first coding region of a group III WRKY transcription factor OsWRKY21 (LOC_Os01g60640). Interestingly, further haplotype analysis showed that C/T difference only existed in the indica group but not in the japonica group, resulting in significant differences in plant height among the different indica rice varieties. OsWRKY21 was expressed in embryo, radicle, shoots, leaves, and stems. Most notably, overexpressing OsWRKY21 resulted in the semi-dwarf phenotype, early heading date and short internodes compared to the wild type, while the knockout mutant plants by CRISPR/Cas9 technology yielded the opposite. The overexpressing lines exhibited the decreased length of the cells near sclerenchyma epidermis, accompanied with the lower levels of indole-3-acetic acid (IAA) and gibberellin 3 (GA3), but increased levels of the abscisic acid (ABA) and salicylic acid (SA) in the internodes at heading stage. Moreover, the semi-dwarf phenotype could be fully rescued by exogenous GA3 application at seedling stage. The RNA-seq and qRT-PCR analysis confirmed the differential expression levels of genes in development and the stress responses in rice, including GA metabolism (GA20ox2, GA2ox6, and YABY1) and cell wall biosynthesis (CesA4, 7, and 9) and regulation (MYB103L). These data suggest the essential role of OsWRKY21 in regulation of internode elongation and plant height in rice.


Assuntos
Oryza/genética , Proteínas de Plantas/genética , Caules de Planta/crescimento & desenvolvimento , Locos de Características Quantitativas , Fatores de Transcrição/genética , Estudo de Associação Genômica Ampla , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Melhoramento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Caules de Planta/genética , Característica Quantitativa Herdável
11.
Gene ; 803: 145899, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34400278

RESUMO

Small-sized and trypanotolerant West African taurine (Bos taurus) cattle are a unique case of human-mediated process of adaptation to a challenging environment. Extensive gene flow with Sahelian zebu (B. indicus), bigger and with some resistance to tick attack, occurred for centuries and allowed the apparition of stable crossbred populations (sanga) having intermediate characteristics. Up to 237 individuals belonging to 10 different taurine, zebu and sanga cattle populations sampled in Benin, Burkina Faso and Niger were typed using the BovineHD BeadChip of Illumina to identify signatures of selection, assessed using three different Extended-Haplotype-Homozygosity-based statistics, overlapping with ancient, originated 1024 or 2048 generations ago, Homozygosity-By-Descent segments in the cattle genome. Candidate genomic regions were defined ensuring their importance within cattle type and using zebu as reference. Functional annotation analysis identified four statistically significant Annotation Clusters in taurine cattle (from ACt1 to ACt4), one (ACs1) in sanga, and another (ACz1) in zebu cattle, fitting well with expectations. ACt1 included genes primarily associated with innate immunity; ACt2 involved bitter taste receptor genes of importance to adaptation to changing environments; ACt3 included 68 genes coding ATP-binding proteins, some of them located on trypanotolerance-related QTL regions, that can partially underlie immune response and the additive mechanism of trypanotolerance; ACt4 was associated with growth and small size (NPPC gene); ACs1 included genes involved in immune response; and ACz1 is related with ectoparasite resistance. Our results provide a new set of genomic areas and candidate genes giving new insights on the genomic impact of adaptation in West African cattle.


Assuntos
Imunidade Adaptativa , Bovinos/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Adaptação Fisiológica , Animais , Benin , Burkina Faso , Resistência à Doença , Fluxo Gênico , Níger , Melhoramento Vegetal , Seleção Genética
12.
Animal ; 15(9): 100341, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34425484

RESUMO

Intramuscular fat content (IFC) is an essential quantitative trait of meat, affecting multiple meat quality indicators. A certain amount of IFC could not only improve the sensory score of pork but also increase the flavour, tenderness, juiciness and shelf-life. To dissect the genetic determinants of IFC, two methods, including genome-wide efficient mixed-model analysis (GEMMA) and linkage disequilibrium adjusted kinships (LDAKs), were used to carry out genome-wide association studies for IFC in Suhuai pig population. A total of 14 and 18 significant single nucleotide polymorphisms (SNPs) were identified by GEMMA and LDAK, respectively. The results of these two methods were highly consistent and all 14 significant SNPs in GEMMA were detected by LDAK. Seven of the 18 SNPs reached the genome-wide significance level (P < 9.85E-07) while 11 cases reached the suggestive significance level (P < 1.77E-05). These significant SNPs were mainly distributed on Sus scrofa chromosome (SSC) 5, 3, and 7. Moreover, one locus resides in a 2.27 Mb (71.37-73.64 Mb) region on SSC5 harbouring 13 significant SNPs associated with IFC, and the lead SNP (rs81302978) also locates in this region. Linkage disequilibrium (LD) analysis showed that there were four pairs of complete LD (r2 = 1) among these 13 SNPs, and the remaining 9 SNPs with incomplete LD (r2 ≠ 1) were selected for subsequent analyses of IFC. Association analyses showed that 7 out of 9 SNPs were significantly associated with IFC (P < 0.05) in 330 Suhuai pigs, and the other 2 SNPs tended to reach a significant association level with IFC (P < 0.1). The phenotypic variance explained (PVE) range of these 9 SNPs was 0.92-3.55%. Meanwhile, the lead SNP was also significantly associated (rs81302978) with IFC (P < 0.05) in 378 commercial hybrid pigs (Pietrain × Duroc) × (Landrace × Yorkshire) (PDLY), and the PVE was 1.38%. Besides, two lipid metabolism-relevant candidate genes, the leucine rich repeat kinase 2 (LRRK2) and PDZ domain containing ring finger 4 (PDZRN4) were identified in the 2.27 Mb region on SSC5. In conclusion, our results may provide a set of markers useful for genetic improvement of IFC in pigs and will advance the genome selection process of IFC on pig breeding programmes.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Animais , Cromossomos Humanos Par 5 , Estudo de Associação Genômica Ampla/veterinária , Humanos , Fenótipo , Locos de Características Quantitativas/genética , Sus scrofa/genética , Suínos
13.
Am J Hum Genet ; 108(9): 1765-1779, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34450030

RESUMO

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.


Assuntos
Colectomia/estatística & dados numéricos , Colite Ulcerativa/cirurgia , Doença de Crohn/cirurgia , Locos de Características Quantitativas , Transcriptoma , Bancos de Espécimes Biológicos , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Colo/metabolismo , Colo/patologia , Colo/cirurgia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Conjuntos de Dados como Assunto , Progressão da Doença , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Herança Multifatorial , Prognóstico , Medição de Risco , Reino Unido
14.
BMC Plant Biol ; 21(1): 388, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416870

RESUMO

BACKGROUND: Soybean is a globally important legume crop that provides a primary source of high-quality vegetable protein and oil. Seed protein content (SPC) is a valuable quality trait controlled by multiple genes in soybean. RESULTS: In this study, we performed quantitative trait loci (QTL) mapping, QTL-seq, and RNA sequencing (RNA-seq) to reveal the genes controlling protein content in the soybean by using the high protein content variety Nanxiadou 25. A total of 50 QTL for SPC distributed on 14 chromosomes except chromosomes 4, 12, 14, 17, 18, and 19 were identified by QTL mapping using 178 recombinant inbred lines (RILs). Among these QTL, the major QTL qSPC_20-1 and qSPC_20-2 on chromosome 20 were repeatedly detected across six tested environments, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. 329 candidate DEGs were obtained within the QTL region of qSPC_20-1 and qSPC_20-2 via gene expression profile analysis. Nine of which were associated with SPC, potentially representing candidate genes. Clone sequencing results showed that different single nucleotide polymorphisms (SNPs) and indels between high and low protein genotypes in Glyma.20G088000 and Glyma.16G066600 may be the cause of changes in this trait. CONCLUSIONS: These results provide the basis for research on candidate genes and marker-assisted selection (MAS) in soybean breeding for seed protein content.


Assuntos
Mapeamento Cromossômico , Estudos de Associação Genética , Proteínas de Plantas/análise , Proteínas de Plantas/genética , Sementes/química , Soja/química , Soja/genética , Produtos Agrícolas/química , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas , Marcadores Genéticos , Variação Genética , Genótipo , Locos de Características Quantitativas , Análise de Sequência de RNA
15.
BMC Plant Biol ; 21(1): 364, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376143

RESUMO

BACKGROUND: Improving the overall production of rice with high quality is a major target of breeders. Mining potential yield-related loci have been geared towards developing efficient rice breeding strategies. In this study, one single-locus genome-wide association studies (SL-GWAS) method (MLM) in conjunction with five multi-locus genome-wide association studies (ML-GWAS) approaches (mrMLM, FASTmrMLM, pLARmEB, pKWmEB, and ISIS EM-BLASSO) were conducted in a panel consisting of 529 rice core varieties with 607,201 SNPs. RESULTS: A total of 152, 106, 12, 111, and 64 SNPs were detected by the MLM model associated with the five yield-related traits, namely grain length (GL), grain width (GW), grain thickness (GT), thousand-grain weight (TGW), and yield per plant (YPP), respectively. Furthermore, 74 significant quantitative trait nucleotides (QTNs) were presented across at least two ML-GWAS methods to be associated with the above five traits successively. Finally, 20 common QTNs were simultaneously discovered by both SL-GWAS and ML-GWAS methods. Based on genome annotation, gene expression analysis, and previous studies, two candidate key genes (LOC_Os09g02830 and LOC_Os07g31450) were characterized to affect GW and TGW, separately. CONCLUSIONS: These outcomes will provide an indication for breeding high-yielding rice varieties in the immediate future.


Assuntos
Estudo de Associação Genômica Ampla , Oryza/crescimento & desenvolvimento , Oryza/genética , Desequilíbrio de Ligação , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
16.
Environ Pollut ; 287: 117586, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34426386

RESUMO

Arsenite [As(III)] toxicity causes impeded growth, inadequate productivity of plants and toxicity through the food chain. Using various chemical residues for priming is one of the approaches in conferring arsenic tolerance in crops. We investigated the mechanism of abscisic acid (ABA)-induced As(III) tolerance in rice genotypes (cv. Swarna and Swarna Sub1) pretreated with 10 µM of ABA for 24 h and transferred into 0, 25 and 50 µM arsenic for 10 days. Plants showed a dose-dependent bioaccumulation of As(III), oxidative stress indicators like superoxide, hydrogen peroxide, thiobarbituric acid reactive substances and the activity of lipoxygenase. As(III) had disrupted cellular redox that reflecting growth indices like net assimilation rate, relative growth rate, specific leaf weight, leaf mass ratio, relative water content, proline, delta-1-pyrroline-5-carboxylate synthetase and electrolyte leakage. ABA priming was more protective in cv. Swarna Sub1 than Swarna for retrieval of total glutathione pool, non-protein thiols, cysteine, phytochelatin and glutathione reductase. Phosphate metabolisms were significantly curtailed irrespective of genotypes where ABA had moderated phosphate uptake and its metabolizing enzymes like acid phosphatase, alkaline phosphatase and H+/ATPase. Rice seedlings had regulated antioxidative potential with the varied polymorphic expression of those enzymes markedly with antioxidative enzymes. The results have given the possible cellular and physiological traits those may interact with ABA priming in the establishment of plant tolerance with As(III) over accumulation and, thereby, its amelioration for oxidative damages. Finally, cv. Swarna Sub1 was identified as a rice genotype as a candidate for breeding program for sustainability against As(III) stress with cellular and physiological traits serving better for selection pressure.


Assuntos
Arsenitos , Oryza , Ácido Abscísico , Arsenitos/toxicidade , Genótipo , Oryza/genética , Locos de Características Quantitativas , Plântula
17.
Genome Biol ; 22(1): 242, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425859

RESUMO

To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.


Assuntos
COVID-19/genética , Proteínas de Membrana Transportadoras/genética , Locos de Características Quantitativas , Receptores CXCR6/genética , Cromossomos Humanos Par 3/genética , Humanos , Fenótipo
18.
Am J Hum Genet ; 108(9): 1647-1668, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34416157

RESUMO

Interpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing quantitative trait locus (e/sQTL) analyses is generally performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements active during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs, and allele-specific expression in cultured cells representing two major developmental stages, primary human neural progenitors (n = 85) and their sorted neuronal progeny (n = 74), identifying numerous loci not detected in either bulk developing cortical wall or adult cortex. Using colocalization and genetic imputation via transcriptome-wide association, we uncover cell-type-specific regulatory mechanisms underlying risk for brain-relevant traits that are active during neocortical differentiation. Specifically, we identified a progenitor-specific eQTL for CENPW co-localized with common variant associations for cortical surface area and educational attainment.


Assuntos
Proteínas Cromossômicas não Histona/genética , Regulação da Expressão Gênica no Desenvolvimento , Neocórtex/metabolismo , Neurogênese/genética , Neurônios/metabolismo , Locos de Características Quantitativas , Alelos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Diferenciação Celular , Cromatina/química , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Mapeamento Cromossômico , Escolaridade , Feminino , Feto , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neuroticismo , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Cultura Primária de Células , Prognóstico , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Esquizofrenia/metabolismo , Transcriptoma
19.
BMC Genomics ; 22(1): 597, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353288

RESUMO

BACKGROUND: Bread wheat (Triticum aestivum L.) is one of the most important cereal food crops for the global population. Spike-layer uniformity (the consistency of the spike distribution in the vertical space)-related traits (SLURTs) are quantitative and have been shown to directly affect yield potential by modifying the plant architecture. Therefore, these parameters are important breeding targets for wheat improvement. The present study is the first genome-wide association study (GWAS) targeting SLURTs in wheat. In this study, a set of 225 diverse spring wheat accessions were used for multi-locus GWAS to evaluate SLURTs, including the number of spikes per plant (NSPP), spike length (SL), number of spikelets per spike (NSPS), grain weight per spike (GWPS), lowest tiller height (LTH), spike-layer thickness (SLT), spike-layer number (SLN) and spike-layer uniformity (SLU). RESULTS: In total, 136 significant marker trait associations (MTAs) were identified when the analysis was both performed individually and combined for two environments. Twenty-nine MTAs were detected in environment one, 48 MTAs were discovered in environment two and 59 MTAs were detected using combined data from the two environments. Altogether, 15 significant MTAs were found for five traits in one of the two environments, and four significant MTAs were detected for the two traits, LTH and SLU, in both environments i.e. E1, E2 and also in combined data from the two environments. In total, 279 candidate genes (CGs) were identified, including Chaperone DnaJ, ABC transporter-like, AP2/ERF, SWEET sugar transporter, as well as genes that have previously been associated with wheat spike development, seed development and grain yield. CONCLUSIONS: The MTAs detected through multi-locus GWAS will be useful for improving SLURTs and thus yield in wheat production through marker-assisted and genomic selection.


Assuntos
Estudo de Associação Genômica Ampla , Triticum , Pão , Fenótipo , Melhoramento Vegetal , Locos de Características Quantitativas , Triticum/genética
20.
BMC Genomics ; 22(1): 596, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353280

RESUMO

BACKGROUND: The eating and cooking qualities (ECQs) of rice (Oryza sativa L.) are key characteristics affecting variety adoption and market value. Starch viscosity profiles tested by a rapid visco analyzer (RVA) offer a direct measure of ECQs and represent the changes in viscosity associated with starch gelatinization. RVA profiles of rice are controlled by a complex genetic system and are also affected by the environment. Although Waxy (Wx) is the major gene controlling amylose content (AC) and ECQs, there are still other unknown genetic factors that affect ECQs. RESULTS: Quantitative trait loci (QTLs) for starch paste viscosity in rice were analyzed using chromosome segment substitution lines (CSSLs) developed from the two cultivars 9311 and Nipponbare, which have same Wx-b allele. Thus, the effect of the major locus Wx was eliminated and the other locus associated with the RVA profile could be identified. QTLs for seven parameters of the starch RVA profile were tested over four years in Nanjing, China. A total of 310 QTLs were identified (from 1 to 55 QTLs per trait) and 136 QTLs were identified in more than one year. Among them, 6 QTLs were stalely detected in four years and 26 QTLs were detected in at least three years including 13 pleiotropic loci, controlling 2 to 6 RVA properties simultaneously. These stable QTL hotspots were co-located with several known starch synthesis-related genes (SSRGs). Sequence alignments showed that nucleotide and amino acid sequences of most SSRGs were different between the two parents. Finally, we detected stable QTLs associated with multiple starch viscosity traits near Wx itself, supporting the notion that additional QTLs near Wx control multiple characteristic values of starch viscosity. CONCLUSIONS: By eliminating the contribution from the major locus Wx, multiple QTLs associated with the RVA profile of rice were identified, several of which were stably detected over four years. The complexity of the genetic basis of rice starch viscosity traits might be due to their pleiotropic effects and the multiple QTL hot spots. Minor QTLs controlling starch viscosity traits were identified by using the chromosome segment substitution strategy. Allele polymorphism might be the reason that QTLs controlling RVA profile characteristics were detected in some known SSRG regions.


Assuntos
Oryza , Amido/química , Alelos , Cromossomos , Oryza/genética , Locos de Características Quantitativas , Viscosidade
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