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1.
Z Kinder Jugendpsychiatr Psychother ; 48(6): 478-489, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33172359

RESUMO

Objective: Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we investigated a four-generation pedigree where transmission of dyslexia is consistent with an autosomal dominant inheritance pattern. Methods: We performed genome wide array-based SNP genotyping and parametric linkage analysis and sequencing analysis of protein-coding exons, exon-intron boundaries and conserved extragenic regions within the haplotype cosegregating with dyslexia in DNA from one affected and one unaffected family member. Cosegregation was confirmed by sequencing all available family members. Additionally, we analyzed 96 dyslexic individuals who had previously shown positive LOD scores on chromosome 4q28 as well as an even larger sample (n = 2591). Results: We found a single prominent linkage interval on chromosome 4q, where sequence analysis revealed a nucleotide variant in the 3' UTR of brain expressed SPRY1 in the dyslexic family member that cosegregated with dyslexia. This sequence alteration might affect the binding efficiency of the IGF2BP1 RNA-binding protein and thus influence the expression level of the SPRY1 gene product. An analysis of 96 individuals from a cohort of dyslexic individuals revealed a second heterozygous variant in this gene, which was absent in the unaffected sister of the proband. An investigation of the region in a much larger sample further found a nominal p-value of 0.0016 for verbal short-term memory (digit span) in 2,591 individuals for a neighboring SNV. After correcting for the local number of analyzed SNVs, and after taking into account linkage disequilibrium, we found this corresponds to a p-value of 0.0678 for this phenotype. Conclusions: We describe a new locus for familial dyslexia and discuss the possibility that SPRY1 might play a role in the etiology of a monogenic form of dyslexia.


Assuntos
Cromossomos Humanos Par 4/genética , Dislexia/genética , Regiões 3' não Traduzidas/genética , Saúde da Família , Humanos , Escore Lod , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Linhagem , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo
2.
PLoS One ; 15(11): e0241535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152019

RESUMO

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5' untranslated region (UTR), 152 within the 3'UTR, 2 within intergenic regions and 34 within coding sequences.


Assuntos
Betacoronavirus/genética , Genoma Viral , Mutação , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Ligação Genética , Desequilíbrio de Ligação , Escore Lod , Análise de Sequência de RNA , Sequenciamento Completo do Genoma
3.
Nat Commun ; 11(1): 3697, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728101

RESUMO

As the number of genomics datasets grows rapidly, sample mislabeling has become a high stakes issue. We present CrosscheckFingerprints (Crosscheck), a tool for quantifying sample-relatedness and detecting incorrectly paired sequencing datasets from different donors. Crosscheck outperforms similar methods and is effective even when data are sparse or from different assays. Application of Crosscheck to 8851 ENCODE ChIP-, RNA-, and DNase-seq datasets enabled us to identify and correct dozens of mislabeled samples and ambiguous metadata annotations, representing ~1% of ENCODE datasets.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Desequilíbrio de Ligação/genética , Bases de Dados de Ácidos Nucleicos , Genótipo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Células K562 , Escore Lod , Anotação de Sequência Molecular
4.
BMC Plant Biol ; 20(1): 213, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398088

RESUMO

BACKGROUND: Muscadine (Muscadinia rotundifolia) is known as a resistance source to many pests and diseases in grapevine. The genetics of its resistance to two major grapevine pests, the phylloxera D. vitifoliae and the dagger nematode X. index, vector of the Grapevine fanleaf virus (GFLV), was investigated in a backcross progeny between the F1 resistant hybrid material VRH8771 (Vitis-Muscadinia) derived from the muscadine R source 'NC184-4' and V. vinifera cv. 'Cabernet-Sauvignon' (CS). RESULTS: In this pseudo-testcross, parental maps were constructed using simple-sequence repeats markers and single nucleotide polymorphism markers from a GBS approach. For the VRH8771 map, 2271 SNP and 135 SSR markers were assembled, resulting in 19 linkage groups (LG) and an average distance between markers of 0.98 cM. Phylloxera resistance was assessed by monitoring root nodosity number in an in planta experiment and larval development in a root in vitro assay. Nematode resistance was studied using 10-12 month long tests for the selection of durable resistance and rating criteria based on nematode reproduction factor and gall index. A major QTL for phylloxera larval development, explaining more than 70% of the total variance and co-localizing with a QTL for nodosity number, was identified on LG 7 and designated RDV6. Additional QTLs were detected on LG 3 (RDV7) and LG 10 (RDV8), depending on the in planta or in vitro experiments, suggesting that various loci may influence or modulate nodosity formation and larval development. Using a Bulked Segregant Analysis approach and a proportion test, markers clustered in three regions on LG 9, LG 10 and LG 18 were shown to be associated to the nematode resistant phenotype. QTL analysis confirmed the results and QTLs were thus designated respectively XiR2, XiR3 and XiR4, although a LOD-score below the significant threshold value was obtained for the QTL on LG 18. CONCLUSIONS: Based on a high-resolution linkage map and a segregating grapevine backcross progeny, the first QTLs for resistance to D. vitifoliae and to X. index were identified from a muscadine source. All together these results open the way to the development of marker-assisted selection in grapevine rootstock breeding programs based on muscadine derived resistance to phylloxera and to X. index in order to delay GFLV transmission.


Assuntos
Resistência à Doença/genética , Hemípteros/fisiologia , Nematoides/fisiologia , Nepovirus/fisiologia , Doenças das Plantas/imunologia , Vitis/genética , Animais , Cruzamento , Mapeamento Cromossômico , Ligação Genética , Genótipo , Escore Lod , Repetições de Microssatélites/genética , Nematoides/virologia , Fenótipo , Doenças das Plantas/parasitologia , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Vitis/imunologia , Vitis/parasitologia
5.
Am J Hum Genet ; 106(6): 793-804, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32413282

RESUMO

Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles (RVs) in the muscle fibers and myopathic changes of differing severity. Inheritance is variable, with either putative autosomal-dominant or autosomal-recessive pattern. Here, using a comprehensive strategy combining whole-genome sequencing (WGS), long-read whole-genome sequencing (LRS), linkage analysis, repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis polymerase chain reaction (AL-PCR), we identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1 in one out of four families and three sporadic case subjects from a Chinese OPDM cohort. Expanded GGC repeats were further confirmed as the cause of OPDM in an additional 2 out of 4 families and 6 out of 13 sporadic Chinese individuals with OPDM, as well as 7 out of 194 unrelated Japanese individuals with OPDM. Methylation, qRT-PCR, and western blot analysis indicated that GIPC1 mRNA levels were increased while protein levels were unaltered in OPDM-affected individuals. RNA sequencing indicated p53 signaling, vascular smooth muscle contraction, ubiquitin-mediated proteolysis, and ribosome pathways were involved in the pathogenic mechanisms of OPDM-affected individuals with GGC repeat expansion in GIPC1. This study provides further evidence that OPDM is associated with GGC repeat expansions in distinct genes and highly suggests that expanded GGC repeat units are essential in the pathogenesis of OPDM, regardless of the genes in which the expanded repeats are located.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Distrofias Musculares/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Cromossomos Humanos Par 19/genética , Metilação de DNA , Feminino , Humanos , Escore Lod , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Linhagem , RNA-Seq , Expansão das Repetições de Trinucleotídeos/genética , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
6.
PLoS One ; 15(2): e0227826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023285

RESUMO

Dietary fibre (DF) has multiple health benefits and wheat grains are major sources of DF for human health. However, DF is depleted in white wheat flour which is more widely consumed than wholegrain. The major DF component in white flour is the cell wall polysaccharide arabinoxylan (AX). We have identified the Chinese wheat cultivar Yumai 34 as having unusually high contents of AX in both water-soluble and insoluble forms. We have therefore used populations generated from crosses between Yumai 34 and four other wheat cultivars, three with average contents of AX (Ukrainka, Altigo and Claire) and one also having unusually high AX (Valoris), in order to map QTLs for soluble AX (determined as relative viscosity of aqueous extracts of wholemeal flours) and total AX (determined by enzyme fingerprinting of white flour). A number of QTL were mapped, but most were only detected in one or two crosses. However, all four crosses showed strong QTLs for high RV/total AX on chromosome 1B, with Yumai 34 being the increasing parent, and a KASP marker for the Yumai 34 high AX allele was validated by analysis of high AX lines derived from Yumai 34 but selected by biochemical analysis. A QTL for RV was also mapped on chromosome 6B in Yumai 34 x Valoris, with Valoris being the increasing allele, which is consistent with the observation of transgressive segregation for this population. Association studies in an independent germplasm panel identified marker trait associations for relative viscosity in these same locations while direct selection for fibre content in breeding resulted in high levels of enrichment for the Yumai 34 1B allele. The data therefore indicate that marker-assisted breeding can be used to develop wheat with high AX fibre in white flour.


Assuntos
Farinha/análise , Locos de Características Quantitativas/genética , Triticum/genética , Xilanos/genética , Alelos , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Escore Lod , Reprodutibilidade dos Testes , Viscosidade
7.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098308

RESUMO

Phomopsis stem canker (PSC) caused by Diaporthe helianthi is increasingly becoming a global threat for sunflower production. In this study, the genetic basis of PSC resistance was investigated in a recombinant inbred line (RIL) population developed from a cross between HA 89 (susceptible) and HA-R3 (resistant). The RIL population was evaluated for PSC disease incidence (DI) in seven screening trials at multiple locations during 2016-2018. The distribution of PSC DI in the RIL population was continuous, confirming a polygenic inheritance of the trait. A moderately high broad-sense heritability (H2, 0.76) was estimated for the trait across environments. In the combined analysis, both the genotype and the genotype × environment interactions were highly significant. A linkage map spanning 1505.33 cM was constructed using genotyping-by-sequencing derived markers. Marker-trait association analysis identified a total of 15 quantitative trait loci (QTL) associated with PSC resistance on 11 sunflower chromosomes, each explaining between 5.24 and 17.39% of the phenotypic variation. PSC resistance QTL were detected in two genomic regions each on chromosomes 3, 5, 13, and 17, while one QTL each was detected in the remaining seven chromosomes. Tightly linked single nucleotide polymorphism (SNP) markers flanking the PSC resistance QTL will facilitate marker-assisted selection in PSC resistance sunflower breeding.


Assuntos
Cromossomos de Plantas/genética , Resistência à Doença/genética , Helianthus/genética , Doenças das Plantas/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Ascomicetos/fisiologia , Mapeamento Cromossômico , Genótipo , Helianthus/classificação , Helianthus/microbiologia , Escore Lod , Fenótipo , Doenças das Plantas/microbiologia
8.
Sci Rep ; 10(1): 1161, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980681

RESUMO

Plumage colouration in birds is important for a plethora of reasons, ranging from camouflage, sexual signalling, and species recognition. The genes underlying colour variation have been vital in understanding how genes can affect a phenotype. Multiple genes have been identified that affect plumage variation, but research has principally focused on major-effect genes (such as those causing albinism, barring, and the like), rather than the smaller effect modifier loci that more subtly influence colour. By utilising a domestic × wild advanced intercross with a combination of classical QTL mapping of red colouration as a quantitative trait and a targeted genetical genomics approach, we have identified five separate candidate genes (CREBBP, WDR24, ARL8A, PHLDA3, LAD1) that putatively influence quantitative variation in red-brown colouration in chickens. By treating colour as a quantitative rather than qualitative trait, we have identified both QTL and genes of small effect. Such small effect loci are potentially far more prevalent in wild populations, and can therefore potentially be highly relevant to colour evolution.


Assuntos
Proteína de Ligação a CREB/genética , Galinhas/genética , Plumas/química , Pigmentação/genética , Locos de Características Quantitativas , Repetições WD40/genética , Animais , Proteína de Ligação a CREB/fisiologia , Galinhas/metabolismo , Mapeamento Cromossômico , Cruzamentos Genéticos , Feminino , Estudos de Associação Genética , Escore Lod , Masculino , Asas de Animais
9.
Theor Appl Genet ; 133(1): 227-237, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31595336

RESUMO

KEY MESSAGE: A QTL for aphid resistance on pepper chromosome 2 was identified and validated. This QTL affects aphid survival and reproduction, and was fine mapped to a locus containing LRR-RLK analogues. Myzus persicae is one of the most threatening insect pests that adversely affects pepper (Capsicum) cultivation. Resistance to aphids was previously identified in Capsicum baccatum. This study aimed at elucidating the genetics of aphid resistance in C. baccatum. A QTL analysis was carried out for M. persicae resistance in an F2 population derived from an intraspecific cross between a highly resistant plant and a susceptible plant. Survival and reproduction were used as resistance parameters. Interval mapping detected two QTLs affecting aphid survival (Rmpas-1) and reproduction (Rmprp-1), respectively, both localized in the same area and sharing the same top marker on chromosome 2. Use of this marker as co-factor in multiple-QTL mapping analysis revealed a second, minor QTL (Rmprp-2) only affecting aphid reproduction, on chromosome 4. Fine mapping confirmed the effects of Rmpas-1 and Rmprp-1 and narrowed the major QTL Rmprp-1 down to a genomic region of 96 kb which is predicted to encode four analogues of resistance genes of the receptor-like kinase family containing a leucine-rich repeat domain (LRR-RLKs). This work provides not only initial information for breeding aphid-resistant pepper varieties, but also forms the basis for future molecular analysis of gene(s) involved in aphid resistance.


Assuntos
Afídeos/fisiologia , Capsicum/genética , Capsicum/parasitologia , Resistência à Doença/genética , Genes de Plantas , Loci Gênicos , Proteínas Serina-Treonina Quinases/genética , Proteínas/genética , Animais , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Escore Lod , Anotação de Sequência Molecular , Locos de Características Quantitativas/genética , Homologia de Sequência de Aminoácidos
10.
Theor Appl Genet ; 133(1): 119-131, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562566

RESUMO

KEY MESSAGE: Genetic dissection of GPC and TKW in tetraploid durum × WEW RIL population, based on high-density SNP genetic map, revealed 12 GPC QTLs and 11 TKW QTLs, with favorable alleles for 11 and 5 QTLs, respectively, derived from WEW. Wild emmer wheat (Triticum turgidum ssp. dicoccoides, WEW) was shown to exhibit high grain protein content (GPC) and therefore possess a great potential for improvement of cultivated wheat nutritional value. Genetic dissection of thousand kernel weight (TKW) and grain protein content (GPC) was performed using a high-density genetic map constructed based on a recombinant inbred line (RIL) population derived from a cross between T. durum var. Svevo and WEW acc. Y12-3. Genotyping of 208 F6 RILs with a 15 K wheat single nucleotide polymorphism (SNP) array yielded 4166 polymorphic SNP markers, of which 1510 were designated as skeleton markers. A total map length of 2169 cM was obtained with an average distance of 1.5 cM between SNPs. A total of 12 GPC QTLs and 11 TKW QTLs were found under five different environments. No significant correlations were found between GPC and TKW across all environments. Four major GPC QTLs with favorable alleles from WEW were found on chromosomes 4BS, 5AS, 6BS and 7BL. The 6BS GPC QTL coincided with the physical position of the NAC transcription factor TtNAM-B1, underlying the cloned QTL, Gpc-B1. Comparisons of the physical intervals of the GPC QTLs described here with the results previously reported in other durum × WEW RIL population led to the discovery of seven novel GPC QTLs. Therefore, our research emphasizes the importance of GPC QTL dissection in diverse WEW accessions as a source of novel alleles for improvement of GPC in cultivated wheat.


Assuntos
Mapeamento Cromossômico , Cruzamentos Genéticos , Meio Ambiente , Proteínas de Grãos/metabolismo , Locos de Características Quantitativas/genética , Sementes/genética , Triticum/genética , Análise de Variância , Cromossomos de Plantas/genética , Endogamia , Escore Lod
11.
PLoS One ; 14(12): e0225010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815953

RESUMO

PURPOSE: To investigate the genetic basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous Pakistani family. METHODS: All participating members of family, PKCC074 underwent an ophthalmic examination. Slit-lamp photographs were ascertained for affected individuals that have not been operated for the removal of the cataractous lens. A small aliquot of the blood sample was collected from all participating individuals and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic short tandem repeat (STR) markers and the logarithm of odds (LOD) scores were calculated. All coding exons and exon-intron boundaries of HSF4 were sequenced and expression of Hsf4 in mouse ocular lens was investigated. The C-terminal FLAG-tagged wild-type and mutant HSF4b constructs were prepared to examine the nuclear localization pattern of the mutant protein. RESULTS: The ophthalmological examinations suggested that nuclear cataracts are present in affected individuals. Genome-wide linkage analyses localized the critical interval to a 10.95 cM (14.17 Mb) interval on chromosome 16q with a maximum two-point LOD score of 4.51 at θ = 0. Sanger sequencing identified a novel missense mutation: c.433G>C (p.Ala145Pro) that segregated with the disease phenotype in the family and was not present in ethnically matched controls. Real-time PCR analysis identified the expression of HSF4 in mouse lens as early as embryonic day 15 with a steady level of expression thereafter. The immunofluorescence tracking confirmed that both wild-type and mutant HSF4 (p.Ala145Pro) proteins localized to the nucleus. CONCLUSION: Here, we report a novel missense mutation in HSF4 associated with arCC in a familial case of Pakistani descent.


Assuntos
Catarata/genética , Ligação Genética , Fatores de Transcrição de Choque Térmico/genética , Cristalino/metabolismo , Repetições de Microssatélites , Mutação de Sentido Incorreto , Animais , Catarata/congênito , Catarata/metabolismo , Consanguinidade , Feminino , Genes Recessivos , Fatores de Transcrição de Choque Térmico/metabolismo , Humanos , Escore Lod , Masculino , Camundongos , Paquistão , Linhagem
12.
Commun Biol ; 2: 461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31840106

RESUMO

Environmental DNA (eDNA) has emerged as a powerful approach for studying marine fisheries and has the potential to negate some of the drawbacks of trawl surveys. However, successful applications in oceanic waters have to date been largely focused on qualitative descriptions of species inventories. Here we conducted a quantitative eDNA survey of Atlantic cod (Gadus morhua) in oceanic waters and compared it with results obtained from a standardized demersal trawl survey. Detection of eDNA originating from Atlantic cod was highly concordant (80%) with trawl catches. We observed significantly positive correlations between the regional integrals of Atlantic cod biomass (kg) and eDNA quantities (copies) (R2 = 0.79, P = 0.003) and between sampling effort-normalised Catch Per Unit Effort (kg hr-1) and eDNA concentrations (copies L-1) (R2 = 0.71, P = 0.008). These findings extend the potential application of environmental DNA to regional biomass assessments of commercially important fish stocks in the ocean.


Assuntos
Biomassa , DNA Ambiental , Gadus morhua , Animais , Ecologia , Ecossistema , Pesqueiros , Gadus morhua/genética , Escore Lod , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes
13.
PLoS One ; 14(10): e0222764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581203

RESUMO

Classical crop models have been developed to predict crop yield and quality, and they are based on physiological and environmental inputs. After molecular discoveries, models should integrate genetic variation to allow predictions that are more genotype-dependent. An interesting approach, Quantitative Trait Locus (QTL)-based ecophysiological modeling, has shown promising results for the design of ideotypes that are adapted to biotic and abiotic stresses, but there are still limitations to attaining a fully integrated model. The aim of this case study is to clarify the impact of choosing different model equations (closely related and with different numbers of parameters) and optimization methods on the detection of QTLs controlling the parameters of crop growth. Different growth equations were parameterized based on a genetic population by following different approaches. The correlations between parameters were analyzed, and two different strategies were adopted to address the correlation issue. QTL analysis was performed on the optimized values of the parameters of the growth equations and on the observed dry mass (DM) data to validate the QTLs detected. Overall, models and strategies resulted in different QTLs being detected. Similar LOD profiles but with peaks of different heights were observed, some of which were significant, resulting in different numbers of QTLs. In some cases, peaks had slightly different positions or were absent. Even closely related growth models led to the detection of different QTLs. The goodness of fit and complexity of the growth models were found to be insufficient to select the best model. Calculating parameters independently of observed data may not be a good strategy, whereas setting parameters independent of the genotype is recommended. Given the large-scale global optimization problem and the strong correlations between parameters, the two algorithms tested showed poor performance. Currently, the lack of effective algorithms is the main obstacle to answering the question posed. The authors therefore suggest testing different model formulations and comparing the QTLs detected before choosing the best formulation to use in an ecophysiological modeling approach based on QTLs.


Assuntos
Modelos Genéticos , Locos de Características Quantitativas/genética , Algoritmos , Biomassa , Frutas/genética , Frutas/crescimento & desenvolvimento , Genótipo , Escore Lod
14.
Sci Rep ; 9(1): 11621, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406157

RESUMO

Carotid intima-media thickness (cIMT) is a subclinical marker for atherosclerosis. Previously, we reported a quantitative trait locus (QTL) for total cIMT on chromosome 14q and identified PRiMA1, FOXN3 and CCDC88C as candidate genes using a common variants (CVs)-based approach. Herein, we further evaluated the genetic contribution of the QTL to cIMT by resequencing. We sequenced all exons within the QTL and genomic regions of PRiMA1, FOXN3 and CCDC88C in Dominican families with evidence for linkage to the QTL. Unrelated Dominicans from the Northern Manhattan Study (NOMAS) were used for validation. Single-variant-based and gene-based analyses were performed for CVs and rare variants (RVs). The strongest evidence for association with CVs was found in PRiMA1 (p = 8.2 × 10-5 in families, p = 0.01 in NOMAS at rs12587586), and in the five-gene cluster SPATA7-PTPN21-ZC3H14-EML5-TTC8 locus (p = 1.3 × 10-4 in families, p = 0.01 in NOMAS at rs2274736). No evidence for association with RVs was found in PRiMA1. The top marker from previous study in PRiMA1 (rs7152362) was associated with fewer atherosclerotic events (OR = 0.67; p = 0.02 in NOMAS) and smaller cIMT (ß = -0.58, p = 2.8 × 10-4 in Family). Within the five-gene cluster, evidence for association was found for exonic RVs (p = 0.02 in families, p = 0.28 in NOMAS), which was enriched among RVs with higher functional potentials (p = 0.05 in NOMAS for RVs in the top functional tertile). In summary, targeted resequencing provided validation and novel insights into the genetic architecture of cIMT, suggesting stronger effects for RVs with higher functional potentials. Furthermore, our data support the clinical relevance of CVs associated with subclinical atherosclerosis.


Assuntos
Aterosclerose/genética , Espessura Intima-Media Carotídea , Ligação Genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Aterosclerose/patologia , Proteínas do Citoesqueleto/genética , Proteínas de Ligação a DNA/genética , República Dominicana , Feminino , Humanos , Escore Lod , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Ligação a Poli(A)/genética , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases não Receptoras/genética , Locos de Características Quantitativas
15.
J Hered ; 110(7): 880-891, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31419284

RESUMO

Multiparental advanced generation intercross (MAGIC) populations provide abundant genetic variation for use in plant genetics and breeding. In this study, we developed a method for quantitative trait locus (QTL) detection in pure-line populations derived from 8-way crosses, based on the principles of inclusive composite interval mapping (ICIM). We considered 8 parents carrying different alleles with different effects. To estimate the 8 genotypic effects, 1-locus genetic model was first built. Then, an orthogonal linear model of phenotypes against marker variables was established to explain genetic effects of the locus. The linear model was estimated by stepwise regression and finally used for phenotype adjustment and background genetic variation control in QTL mapping. Simulation studies using 3 genetic models demonstrated that the proposed method had higher detection power, lower false discovery rate (FDR), and unbiased estimation of QTL locations compared with other methods. Marginal bias was observed in the estimation of QTL effects. An 8-parental recombinant inbred line (RIL) population previously reported in cowpea and analyzed by interval mapping (IM) was reanalyzed by ICIM and genome-wide association mapping implemented in software FarmCPU. The results indicated that ICIM identified more QTLs explaining more phenotypic variation than did IM; ICIM provided more information on the detected QTL than did FarmCPU; and most QTLs identified by IM and FarmCPU were also detected by ICIM.


Assuntos
Mapeamento Cromossômico , Cruzamentos Genéticos , Genética Populacional , Modelos Genéticos , Locos de Características Quantitativas , Algoritmos , Endogamia , Escore Lod , Vigna/genética
16.
J Genet Genomics ; 46(7): 343-352, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-31378650

RESUMO

Precise mapping of quantitative trait loci (QTLs) is critical for assessing genetic effects and identifying candidate genes for quantitative traits. Interval and composite interval mappings have been the methods of choice for several decades, which have provided tools for identifying genomic regions harboring causal genes for quantitative traits. Historically, the concept was developed on the basis of sparse marker maps where genotypes of loci within intervals could not be observed. Currently, genomes of many organisms have been saturated with markers due to the new sequencing technologies. Genotyping by sequencing usually generates hundreds of thousands of single nucleotide polymorphisms (SNPs), which often include the causal polymorphisms. The concept of interval no longer exists, prompting the necessity of a norm change in QTL mapping technology to make use of the high-volume genomic data. Here we developed a statistical method and a software package to map QTLs by binning markers into haplotype blocks, called bins. The new method detects associations of bins with quantitative traits. It borrows the mixed model methodology with a polygenic control from genome-wide association studies (GWAS) and can handle all kinds of experimental populations under the linear mixed model (LMM) framework. We tested the method using both simulated data and data from populations of rice. The results showed that this method has higher power than the current methods. An R package named binQTL is available from GitHub.


Assuntos
Mapeamento Cromossômico , Genótipo , Locos de Características Quantitativas , Ligação Genética , Genética Populacional , Estudo de Associação Genômica Ampla , Escore Lod , Oryza/genética , Curva ROC
17.
Proc Natl Acad Sci U S A ; 116(32): 16062-16067, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31337678

RESUMO

The regulatory network of genes and molecules in sleep/wakefulness remains to be elucidated. Here we describe the methodology and workflow of the dominant screening of randomly mutagenized mice and discuss theoretical basis of forward genetics research for sleep in mice. Our high-throughput screening employs electroencephalogram (EEG) and electromyogram (EMG) to stage vigilance states into a wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS). Based on their near-identical sleep/wake behavior, C57BL/6J (B6J) and C57BL/6N (B6N) are chosen as mutagenized and counter strains, respectively. The total time spent in the wake and NREMS, as well as the REMS episode duration, shows sufficient reproducibility with small coefficients of variance, indicating that these parameters are most suitable for quantitative phenotype-driven screening. Coarse linkage analysis of the quantitative trait, combined with whole-exome sequencing, can identify the gene mutation associated with sleep abnormality. Our simulations calculate the achievable LOD score as a function of the phenotype strength and the numbers of mice examined. A pedigree showing a mild decrease in total wake time resulting from a heterozygous point mutation in the Cacna1a gene is described as an example.


Assuntos
Testes Genéticos/métodos , Sono/genética , Vigília/genética , Animais , Canais de Cálcio Tipo N/genética , Simulação por Computador , Cruzamentos Genéticos , Distúrbios do Sono por Sonolência Excessiva/genética , Etilnitrosoureia , Feminino , Genes Dominantes , Homozigoto , Escore Lod , Masculino , Camundongos Endogâmicos C57BL , Mutação/genética , Linhagem , Fenótipo , Reprodutibilidade dos Testes
18.
Int J Mol Sci ; 20(13)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277435

RESUMO

High-intensity ultraviolet-B (UV-B) irradiation is a complex abiotic stressor resulting in excessive light exposure, heat, and dehydration, thereby affecting crop yields. In the present study, we identified quantitative trait loci (QTLs) for resistance to high-intensity UV-B irradiation in soybean (Glycine max [L.]). We used a genotyping-by-sequencing approach using an F6 recombinant inbred line (RIL) population derived from a cross between Cheongja 3 (UV-B sensitive) and Buseok (UV-B resistant). We evaluated the degree of leaf damage by high-intensity UV-B radiation in the RIL population and identified four QTLs, UVBR12-1, 6-1, 10-1, and 14-1, for UV-B stress resistance, together explaining 20% of the observed phenotypic variation. The genomic regions containing UVBR12-1 and UVBR6-1 and their syntenic blocks included other known biotic and abiotic stress-related QTLs. The QTL with the highest logarithm of odds (LOD) score of 3.76 was UVBR12-1 on Chromosome 12, containing two genes encoding spectrin beta chain, brain (SPTBN, Glyma.12g088600) and bZIP transcription factor21/TGACG motif-binding 9 (bZIP TF21/TGA9, Glyma.12g088700). Their amino acid sequences did not differ between the mapping parents, but both genes were significantly upregulated by UV-B stress in Buseok but not in Cheongja 3. Among five genes in UVBR6-1 on Chromosome 6, Glyma.06g319700 (encoding a leucine-rich repeat family protein) had two nonsynonymous single nucleotide polymorphisms differentiating the parental lines. Our findings offer powerful genetic resources for efficient and precise breeding programs aimed at developing resistant soybean cultivars to multiple stresses. Furthermore, functional validation of the candidate genes will improve our understanding of UV-B stress defense mechanisms.


Assuntos
Locos de Características Quantitativas/genética , Tolerância a Radiação/genética , Soja/genética , Soja/efeitos da radiação , Raios Ultravioleta , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Ligação Genética , Genoma de Planta , Endogamia , Escore Lod , Fenótipo , Folhas de Planta/efeitos da radiação , Polimorfismo de Nucleotídeo Único/genética , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Sintenia/genética
19.
Mol Ecol ; 28(17): 3942-3957, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31283079

RESUMO

How a host fights infection depends on an ordered sequence of steps, beginning with attempts to prevent a pathogen from establishing an infection, through to steps that mitigate a pathogen's control of host resources or minimize the damage caused during infection. Yet empirically characterizing the genetic basis of these steps remains challenging. Although each step is likely to have a unique genetic and environmental signature, and may therefore respond to selection in different ways, events that occur earlier in the infection process can mask or overwhelm the contributions of subsequent steps. In this study, we dissect the genetic architecture of a stepwise infection process using a quantitative trait locus (QTL) mapping approach. We control for variation at the first line of defence against a bacterial pathogen and expose downstream genetic variability related to the host's ability to mitigate the damage pathogens cause. In our model, the water-flea Daphnia magna, we found a single major effect QTL, explaining 64% of the variance, that is linked to the host's ability to completely block pathogen entry by preventing their attachment to the host oesophagus; this is consistent with the detection of this locus in previous studies. In susceptible hosts allowing attachment, however, a further 23 QTLs, explaining between 5% and 16% of the variance, were mapped to traits related to the expression of disease. The general lack of pleiotropy and epistasis for traits related to the different stages of the infection process, together with the wide distribution of QTLs across the genome, highlights the modular nature of a host's defence portfolio, and the potential for each different step to evolve independently. We discuss how isolating the genetic basis of individual steps can help to resolve discussion over the genetic architecture of host resistance.


Assuntos
Daphnia/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Pasteuria/genética , Animais , Variação Genética , Genótipo , Infecções por Bactérias Gram-Positivas/prevenção & controle , Escore Lod , Fenótipo , Locos de Características Quantitativas/genética
20.
Theor Appl Genet ; 132(8): 2325-2351, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172227

RESUMO

Allohexaploid (2n = 6x = 42) intermediate wheatgrass (Thinopyrum intermedium), abbreviated IWG, is an outcrossing perennial grass belonging to the tertiary gene pool of wheat. Perenniality would be valuable option for grain production, but attempts to introgress this complex trait from wheat-Thinopyrum hybrids have not been commercially successful. Efforts to breed IWG itself as a dual-purpose forage and grain crop have demonstrated useful progress and applications, but grain yields are significantly less than wheat. Therefore, genetic and physical maps have been developed to accelerate domestication of IWG. Herein, these maps were used to identify quantitative trait loci (QTLs) and candidate genes associated with IWG grain production traits in a family of 266 full-sib progenies derived from two heterozygous parents, M26 and M35. Transgressive segregation was observed for 17 traits related to seed size, shattering, threshing, inflorescence capacity, fertility, stem size, and flowering time. A total of 111 QTLs were detected in 36 different regions using 3826 genotype-by-sequence markers in 21 linkage groups. The most prominent QTL had a LOD score of 15 with synergistic effects of 29% and 22% over the family means for seed retention and percentage of naked seeds, respectively. Many QTLs aligned with one or more IWG gene models corresponding to 42 possible domestication orthogenes including the wheat Q and RHT genes. A cluster of seed-size and fertility QTLs showed possible alignment to a putative Z self-incompatibility gene, which could have detrimental grain-yield effects when genetic variability is low. These findings elucidate pathways and possible hurdles in the domestication of IWG.


Assuntos
Agropyron/genética , Mapeamento Cromossômico , Domesticação , Locos de Características Quantitativas/genética , Característica Quantitativa Herdável , Sequência de Bases , Cromossomos de Plantas/genética , Ligação Genética , Marcadores Genéticos , Genoma de Planta , Genótipo , Escore Lod , Fenótipo
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