Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.142
Filtrar
1.
Nat Commun ; 12(1): 5477, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531386

RESUMO

Evolutionary constraints may significantly bias phenotypic change, while "breaking" from such constraints can lead to expanded ecological opportunity. Ray-finned fishes have broken functional constraints by developing two jaws (oral-pharyngeal), decoupling prey capture (oral jaw) from processing (pharyngeal jaw). It is hypothesized that the oral and pharyngeal jaws represent independent evolutionary modules and this facilitated diversification in feeding architectures. Here we test this hypothesis in African cichlids. Contrary to our expectation, we find integration between jaws at multiple evolutionary levels. Next, we document integration at the genetic level, and identify a candidate gene, smad7, within a pleiotropic locus for oral and pharyngeal jaw shape that exhibits correlated expression between the two tissues. Collectively, our data show that African cichlid evolutionary success has occurred within the context of a coupled jaw system, an attribute that may be driving adaptive evolution in this iconic group by facilitating rapid shifts between foraging habitats, providing an advantage in a stochastic environment such as the East African Rift-Valley.


Assuntos
Evolução Biológica , Ciclídeos/anatomia & histologia , Comportamento Alimentar/fisiologia , Arcada Osseodentária/anatomia & histologia , Boca/anatomia & histologia , Faringe/anatomia & histologia , Animais , Ciclídeos/genética , Ecossistema , Feminino , Escore Lod , Masculino , Locos de Características Quantitativas/genética , Análise de Sequência de DNA/métodos , Microtomografia por Raio-X
2.
Hum Genet ; 140(8): 1183-1200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34076780

RESUMO

Dyslexia is a common heritable developmental disorder involving impaired reading abilities. Its genetic underpinnings are thought to be complex and heterogeneous, involving common and rare genetic variation. Multigenerational families segregating apparent monogenic forms of language-related disorders can provide useful entrypoints into biological pathways. In the present study, we performed a genome-wide linkage scan in a three-generational family in which dyslexia affects 14 of its 30 members and seems to be transmitted with an autosomal dominant pattern of inheritance. We identified a locus on chromosome 7q21.11 which cosegregated with dyslexia status, with the exception of two cases of phenocopy (LOD = 2.83). Whole-genome sequencing of key individuals enabled the assessment of coding and noncoding variation in the family. Two rare single-nucleotide variants (rs144517871 and rs143835534) within the first intron of the SEMA3C gene cosegregated with the 7q21.11 risk haplotype. In silico characterization of these two variants predicted effects on gene regulation, which we functionally validated for rs144517871 in human cell lines using luciferase reporter assays. SEMA3C encodes a secreted protein that acts as a guidance cue in several processes, including cortical neuronal migration and cellular polarization. We hypothesize that these intronic variants could have a cis-regulatory effect on SEMA3C expression, making a contribution to dyslexia susceptibility in this family.


Assuntos
Dislexia/genética , Predisposição Genética para Doença , Padrões de Herança , Polimorfismo de Nucleotídeo Único , Semaforinas/genética , Sequência de Bases , Movimento Celular , Cromossomos Humanos Par 7 , Dislexia/diagnóstico por imagem , Dislexia/metabolismo , Dislexia/fisiopatologia , Família , Feminino , Expressão Gênica , Genes Dominantes , Ligação Genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Íntrons , Escore Lod , Masculino , Neuroimagem , Neurônios/metabolismo , Neurônios/patologia , Linhagem , Fenótipo , Semaforinas/deficiência , Sequenciamento Completo do Genoma
3.
Sci Rep ; 11(1): 9004, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903705

RESUMO

Glucoraphanin is a major secondary metabolite found in Brassicaceae vegetables, especially broccoli, and its degradation product sulforaphane plays an essential role in anticancer. The fine mapping of sulforaphane metabolism quantitative trait loci (QTLs) in broccoli florets is necessary for future marker-assisted selection strategies. In this study, we utilized a doubled haploid population consisting of 176 lines derived from two inbred lines (86,101 and 90,196) with significant differences in sulforaphane content, coupled with extensive genotypic and phenotypic data from two independent environments. A linkage map consisting of 438 simple sequence repeats markers was constructed, covering a length of 1168.26 cM. A total of 18 QTLs for sulforaphane metabolism in broccoli florets were detected, 10 were detected in 2017, and the other 8 were detected in 2018. The LOD values of all QTLs ranged from 3.06 to 14.47, explaining 1.74-7.03% of the biochemical variation between two years. Finally, 6 QTLs (qSF-C3-1, qSF-C3-2, qSF-C3-3, qSF-C3-5, qSF-C3-6 and qSF-C7) were stably detected in more than one environment, each accounting for 4.54-7.03% of the phenotypic variation explained (PVE) and a total of 30.88-34.86% of PVE. Our study provides new insights into sulforaphane metabolism in broccoli florets and marker-assisted selection breeding in Brassica oleracea crops.


Assuntos
Brassica/genética , Brassica/metabolismo , Mapeamento Cromossômico , Genética Populacional , Haploidia , Isotiocianatos/metabolismo , Locos de Características Quantitativas , Sulfóxidos/metabolismo , Biomarcadores , Ligação Genética , Padrões de Herança , Escore Lod
4.
G3 (Bethesda) ; 11(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33638985

RESUMO

Quantitative trait loci (QTL) hotspots (genomic locations enriched in QTL) are a common and notable feature when collecting many QTL for various traits in many areas of biological studies. The QTL hotspots are important and attractive since they are highly informative and may harbor genes for the quantitative traits. So far, the current statistical methods for QTL hotspot detection use either the individual-level data from the genetical genomics experiments or the summarized data from public QTL databases to proceed with the detection analysis. These methods may suffer from the problems of ignoring the correlation structure among traits, neglecting the magnitude of LOD scores for the QTL, or paying a very high computational cost, which often lead to the detection of excessive spurious hotspots, failure to discover biologically interesting hotspots composed of a small-to-moderate number of QTL with strong LOD scores, and computational intractability, respectively, during the detection process. In this article, we describe a statistical framework that can handle both types of data as well as address all the problems at a time for QTL hotspot detection. Our statistical framework directly operates on the QTL matrix and hence has a very cheap computational cost and is deployed to take advantage of the QTL mapping results for assisting the detection analysis. Two special devices, trait grouping and top γn,α profile, are introduced into the framework. The trait grouping attempts to group the traits controlled by closely linked or pleiotropic QTL together into the same trait groups and randomly allocates these QTL together across the genomic positions separately by trait group to account for the correlation structure among traits, so as to have the ability to obtain much stricter thresholds and dismiss spurious hotspots. The top γn,α profile is designed to outline the LOD-score pattern of QTL in a hotspot across the different hotspot architectures, so that it can serve to identify and characterize the types of QTL hotspots with varying sizes and LOD-score distributions. Real examples, numerical analysis, and simulation study are performed to validate our statistical framework, investigate the detection properties, and also compare with the current methods in QTL hotspot detection. The results demonstrate that the proposed statistical framework can effectively accommodate the correlation structure among traits, identify the types of hotspots, and still keep the notable features of easy implementation and fast computation for practical QTL hotspot detection.


Assuntos
Locos de Características Quantitativas , Mapeamento Cromossômico , Simulação por Computador , Escore Lod , Fenótipo
5.
J Bioinform Comput Biol ; 19(1): 2050044, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33472570

RESUMO

Multivariate simple interval mapping (SIM) is one of the most popular approaches for multiple quantitative trait locus (QTL) analysis. Both maximum likelihood (ML) and least squares (LS) multivariate regression (MVR) are widely used methods for multi-trait SIM. ML-based MVR (MVR-ML) is an expectation maximization (EM) algorithm based iterative and complex time-consuming approach. Although the LS-based MVR (MVR-LS) approach is not an iterative process, the calculation of likelihood ratio (LR) statistic in MVR-LS is also a time-consuming complex process. We have introduced a new approach (called FastMtQTL) for multi-trait QTL analysis based on the assumption of multivariate normal distribution of phenotypic observations. Our proposed method can identify almost the same QTL positions as those identified by the existing methods. Moreover, the proposed method takes comparatively less computation time because of the simplicity in the calculation of LR statistic by this method. In the proposed method, LR statistic is calculated only using the sample variance-covariance matrix of phenotypes and the conditional probability of QTL genotype given the marker genotypes. This improvement in computation time is advantageous when the numbers of phenotypes and individuals are larger, and the markers are very dense resulting in a QTL mapping with a bigger dataset.


Assuntos
Algoritmos , Modelos Genéticos , Locos de Características Quantitativas , Animais , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla , Genótipo , Hordeum/genética , Escore Lod , Camundongos , Fenótipo , Análise de Regressão , Software
6.
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 , SARS-CoV-2 , Análise de Sequência de RNA , Sequenciamento Completo do Genoma
7.
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
8.
J Speech Lang Hear Res ; 63(12): 4046-4061, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33186502

RESUMO

Purpose Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions These results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI. Supplemental Material https://doi.org/10.23641/asha.13203218.


Assuntos
Transtorno Específico de Linguagem , Mapeamento Cromossômico , Predisposição Genética para Doença/genética , Humanos , Escore Lod , Linhagem
9.
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
10.
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 , 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
11.
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
12.
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
13.
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
14.
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
15.
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/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
16.
Cancer Epidemiol Biomarkers Prev ; 29(2): 434-442, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31826912

RESUMO

BACKGROUND: Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer. METHODS: Parametric genetic linkage analysis was performed on these samples using two distinct analyses-the lung cancer only (LCO) analysis, where only patients with lung cancer were coded as affected, and the all aggregated cancers (AAC) analysis, where other cancers seen in the pedigree were coded as affected. RESULTS: The AAC analysis yielded a genome-wide significant result at rs61943670 in POLR3B at 12q23.3. POLR3B has been implicated somatically in lung cancer, but this germline finding is novel and is a significant expression quantitative trait locus in lung tissue. Interesting genome-wide suggestive haplotypes were also found within individual families, particularly near SSPO at 7p36.1 in one family and a large linked haplotype spanning 4q21.3-28.3 in a different family. The 4q haplotype contains potential causal rare variants in DSPP at 4q22.1 and PTPN13 at 4q21.3. CONCLUSIONS: Regions on 12q, 7p, and 4q are linked to increased cancer risk in highly aggregated lung cancer families, 12q across families and 7p and 4q within a single family. POLR3B, SSPO, DSPP, and PTPN13 are currently the best candidate genes. IMPACT: Functional work on these genes is planned for future studies and if confirmed would lead to potential biomarkers for risk in cancer.


Assuntos
Cromossomos Humanos Par 12/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , RNA Polimerase III/genética , Moléculas de Adesão Celular Neuronais/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 7/genética , Proteínas da Matriz Extracelular/genética , Feminino , Haplótipos , Humanos , Escore Lod , Masculino , Anamnese , Linhagem , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 13/genética , Locos de Características Quantitativas , Fatores de Risco , Sialoglicoproteínas/genética , Sequenciamento Completo do Exoma
17.
Addiction ; 115(3): 482-492, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31833150

RESUMO

BACKGROUND AND AIMS: The use of cannabis has previously been linked to both depression and self-harm; however, the role of genetics in this relationship is unclear. This study aimed to estimate the phenotypic and genetic associations between cannabis use and depression and self-harm. DESIGN: Cross-sectional data collected through UK Biobank were used to test the phenotypic association between cannabis use, depression and self-harm. UK Biobank genetic data were then combined with consortia genome-wide association study summary statistics to further test the genetic relationships between these traits using LD score regression, polygenic risk scoring and Mendelian randomization methods. SETTING: United Kingdom, with additional international consortia data. PARTICIPANTS: A total of 126 291 British adults aged between 40 and 70 years, recruited into UK Biobank. MEASUREMENTS: Phenotypic outcomes were life-time history of cannabis use (including initial and continued cannabis use), depression (including single-episode and recurrent depression) and self-harm. Genome-wide genetic data were used and assessment centre, batch and the first six principal components were included as key covariates when handling genetic data. FINDINGS: In UK Biobank, cannabis use is associated with an increased likelihood of depression [odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.59-1.70] and self-harm (OR = 2.85, 95% CI = 2.69-3.01). The strength of this phenotypic association is stronger when more severe trait definitions of cannabis use and depression are considered. Using consortia genome-wide summary statistics, significant genetic correlations are seen between cannabis use and depression [rg = 0.289, standard error (SE) = 0.036]. Polygenic risk scores for cannabis use and depression explain a small but significant proportion of variance in cannabis use, depression and self-harm within a UK Biobank target sample. However, two-sample Mendelian randomization analyses were not significant. CONCLUSIONS: Cannabis use appeared to be both phenotypically and genetically associated with depression and self-harm. Limitations in statistical power mean that conclusions could not be made on the direction of causality between these traits.


Assuntos
Cannabis , Depressão/genética , Uso da Maconha/genética , Fenótipo , Comportamento Autodestrutivo/genética , Adulto , Idoso , Bancos de Espécimes Biológicos , Estudos Transversais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Escore Lod , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Herança Multifatorial , Reino Unido
18.
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
19.
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 , Gadus morhua , Animais , Ecologia , Ecossistema , Pesqueiros , Gadus morhua/genética , Escore Lod , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...