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1.
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
2.
J Genet ; 98(2)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31204700

RESUMO

Panicle traits are the most important agronomic characters which directly relate to yield in rice. Panicle length (PL) being one of the major components of rice panicle structure is controlled by quantitative trait loci (QTLs). In our research, conducted at Research Farm of SKUAST-J, crosses of parental lines K343 and DHMAS were made for generating F2 mapping population, which were then transplanted into the field using augmented design-I. The F2 population was used for phenotypic evaluation, development of linkage map and identification of QTLs on the chromosomes by using SSR markers. A total of 450 SSR markers were used for screening both the parents of which 53 highly polymorphic markers were selected and used for genotyping of 233 genotypes of F2population. Linkage map was generated using MAPMAKER/EXP3.0 software, seven linkage groups were found distributed on 11 chromosomes of rice. QTLs were detected using QTL Cartographer (v2.5) software. Based on 1000 permutation tests, a logarithm of odds (LOD) threshold value 2.0 and 3.0 was set. Composite interval mapping was used to map QTLs in populations derived from bi-parental crosses. The phenotypic data, genotypic data and the genetic linkage map generated identified total three QTLs of which one was identified for PL qPL2, located at 85.01 cM position with 2.1 LOD value and in between the marker intervals RM324-RM208, this QTL explained the phenotype variation by 4.36%. The other two QTLs were identified for spikelet density (SD) qSD3.1 and qSD3.2, located at 28.91 and 39.51 cM, respectively, both with a flanking marker RM6832 on chromosome 3. The LOD value and phenotypic variation explained for qSD3.1 and qSD3.2 was 3.00 and 3.25; 9.70 and 12.34% respectively. The reported QTLs identified in the study suggested a less diversity in the parents used and also the rejection of not so useful markers from the used set of markers for PL and SD.


Assuntos
Genética Populacional , Oryza/genética , Locos de Características Quantitativas , Mapeamento Cromossômico , Ligação Genética , Genótipo , Escore Lod , Oryza/classificação , Fenótipo , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico
3.
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
4.
Hum Genet ; 138(10): 1077-1090, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31172260

RESUMO

High hyperopia is a common and severe form of refractive error. Genetic factors play important roles in the development of high hyperopia but the exact gene responsible for this condition is mostly unknown. We identified a large Chinese family with autosomal dominant high hyperopia. A genome-wide linkage scan mapped the high hyperopia to chromosome 11p12-q13.3, with maximum log of the odds scores of 4.68 at theta = 0 for D11S987. Parallel whole-exome sequencing detected a novel c.3377delG (p.Gly1126Valfs*31) heterozygous mutation in the MYRF gene within the linkage interval. Whole-exome sequencing in other 121 probands with high hyperopia identified additional novel mutations in MYRF within two other families: a de novo c.3274_3275delAG (p.Leu1093Profs*22) heterozygous mutation and a c.3194+2T>C heterozygous mutation. All three mutations are located in the C-terminal region of MYRF and are predicted to result in truncation of that portion. Two patients from two of the three families developed angle-closure glaucoma. These three mutations were present in neither the ExAC database nor our in-house whole-exome sequencing data from 3280 individuals. No other truncation mutations in MYRF were detected in the 3280 individuals. Knockdown of myrf resulted in small eye size in zebrafish. These evidence all support that truncation mutations in the C-terminal region of MYRF are responsible for autosomal dominant high hyperopia in these families. Our results may provide useful clues for further understanding the functional role of the C-terminal region of this critical myelin regulatory factor, as well as the molecular pathogenesis of high hyperopia and its associated angle-closure glaucoma.


Assuntos
Cromossomos Humanos Par 11 , Oftalmopatias Hereditárias/genética , Genes Dominantes , Estudos de Associação Genética , Predisposição Genética para Doença , Hiperopia/genética , Proteínas de Membrana/genética , Mutação , Fatores de Transcrição/genética , Animais , Mapeamento Cromossômico , Análise Mutacional de DNA , Oftalmopatias Hereditárias/diagnóstico , Feminino , Angiofluoresceinografia , Técnicas de Inativação de Genes , Loci Gênicos , Humanos , Hiperopia/diagnóstico , Escore Lod , Masculino , Linhagem , Fenótipo , Peixe-Zebra
5.
J Diabetes Res ; 2019: 2310235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089471

RESUMO

Measurements of fasting glucose (FG) or glycated hemoglobin A1c (HbA1c) are two clinically approved approaches commonly used to determine glycemia, both of which are influenced by genetic factors. Obtaining accurate measurements of FG or HbA1c is not without its challenges, though. Measuring glycated serum protein (GSP) offers an alternative approach for assessing glycemia. The aim of this study was to estimate the heritability of GSP and GSP expressed as a percentage of total serum albumin (%GA) using a variance component approach and localize genomic regions (QTLs) that harbor genes likely to influence GSP and %GA trait variation in a large extended multigenerational pedigree from Jiri, Nepal (n = 1,800). We also performed quantitative bivariate analyses to assess the relationship between GSP or %GA and several cardiometabolic traits. Additive genetic effects significantly influence variation in GSP and %GA levels (p values: 1.15 × 10-5 and 3.39 × 10-5, respectively). We localized a significant (LOD score = 3.18) and novel GSP QTL on chromosome 11q, which has been previously linked to type 2 diabetes. Two common (MAF > 0.4) SNPs within the chromosome 11 QTL were associated with GSP (adjusted pvalue < 5.87 × 10-5): an intronic variant (rs10790184) in the DSCAML1 gene and a 3'UTR variant (rs8258) in the CEP164 gene. Significant positive correlations were observed between GSP or %GA and blood pressure, and lipid traits (p values: 0.0062 to 1.78 × 10-9). A significant negative correlation was observed between %GA and HDL cholesterol (p = 1.12 × 10-5). GSP is influenced by genetic factors and can be used to assess glycemia and diabetes risk. Thus, GSP measurements can facilitate glycemic studies when accurate FG and/or HbA1c measurements are difficult to obtain. GSP can also be measured from frozen blood (serum) samples, which allows the prospect of retrospective glycemic studies using archived samples.


Assuntos
Glicemia/análise , Proteínas Sanguíneas/genética , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , HDL-Colesterol/sangue , Saúde da Família , Feminino , Predisposição Genética para Doença , Genótipo , Hemoglobina A Glicada/genética , Glicosilação , Humanos , Hiperglicemia , Hipoglicemia/sangue , Lipídeos/sangue , Lipídeos/química , Escore Lod , Masculino , Pessoa de Meia-Idade , Nepal , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise , Adulto Jovem
6.
G3 (Bethesda) ; 9(7): 2317-2324, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31092608

RESUMO

The high mapping resolution of multiparental populations, combined with technology to measure tens of thousands of phenotypes, presents a need for quantitative methods to enhance understanding of the genetic architecture of complex traits. When multiple traits map to a common genomic region, knowledge of the number of distinct loci provides important insight into the underlying mechanism and can assist planning for subsequent experiments. We extend the method of Jiang and Zeng (1995), for testing pleiotropy with a pair of traits, to the case of more than two alleles. We also incorporate polygenic random effects to account for population structure. We use a parametric bootstrap to determine statistical significance. We apply our methods to a behavioral genetics data set from Diversity Outbred mice. Our methods have been incorporated into the R package qtl2pleio.


Assuntos
Cruzamentos Genéticos , Pleiotropia Genética , Genética Populacional , Locos de Características Quantitativas , Algoritmos , Simulação por Computador , Escore Lod , Modelos Genéticos , Herança Multifatorial
7.
BMC Plant Biol ; 19(1): 153, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014249

RESUMO

BACKGROUND: Fusarium crown rot (FCR) is a severe and chronic disease in common wheat and is able to cause serious yield loss and health problems to human and livestock. RESULTS: Here, 234 Chinese wheat cultivars were evaluated in four greenhouse experiments for FCR resistance and genome-wide association studies (GWAS) were performed using the wheat 660 K genotyping assay. The results indicated that most cultivars evaluated showed FCR disease index (DI) of 40-60, while some cultivars showed stably good FCR resistance (DI < 30). GWAS identified 286 SNPs to be significantly associated with FCR resistance, of which 266, 6 and 8 were distributed on chromosomes 6A, 6B and 6D, respectively. The significant SNPs on 6A were located in a 7.0-Mb region containing 51 annotated genes. On the other hand, QTL mapping using a bi-parental population derived from UC1110 and PI610750 detected three QTLs on chromosomes 6A (explaining 7.77-10.17% of phenotypic variation), 2D (7.15-9.29%) and 2A (5.24-6.92%). The 6A QTL in the UC1110/PI610750 population falls into the same chromosomal region as those detected from GWAS, demonstrating its importance in Chinese materials for FCR resistance. CONCLUSION: This study could provide useful information for utilization of FCR-resistant wheat germplasm and further understanding of molecular and genetics basis of FCR resistance in common wheat.


Assuntos
Resistência à Doença/genética , Fusarium/fisiologia , Genoma de Planta , Estudo de Associação Genômica Ampla , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Triticum/genética , Triticum/microbiologia , Alelos , Cromossomos de Plantas/genética , Haplótipos/genética , Endogamia , Escore Lod , Fenótipo , Doenças das Plantas/imunologia , Polimorfismo de Nucleotídeo Único/genética , Análise de Componente Principal , Locos de Características Quantitativas/genética , Triticum/imunologia
8.
Electrophoresis ; 40(11): 1540-1549, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30838663

RESUMO

In this study, GC-MS- and MEKC-based methods for determination of caffeine (CAF) in preworkout supplements were developed and validated. The proposed protocols utilized minimal sample preparation (simple dilution and syringe filtration). The developed methods achieved satisfactory validation parameters, i.e. good linearity (R2 > 0.9988 and R2 > 0.9985 for GC-MS- and MEKC-based method, respectively), satisfactory intra- and interaccuracy (within 92.6-100.7% for method utilizing GC-MS and 92.1-110.3% for protocol based on MEKC) and precision (CV < 15.9% and CV < 6.3% for GC-MS- and MEKC-based method, respectively) and recovery (within 100.1-100.8% for method utilizing GC-MS and 101.5-106.2% for protocol based on MEKC). The LOD was 0.03 and 3 µg/mL for method utilizing GC-MS and MEKC, respectively. The CAF concentrations determined by GC-MS- and MEKC-based methods were found to be in the range of 8.53-11.23 and 8.20-11.61 µg/mL, respectively. Taking into consideration information on the labels, the investigated supplements were found to contain from 110.0 to 167.3% of the declared CAF content, which confirmed the literature reports on incompatibility of the declared product compositions with real ones. Nevertheless, the consumption of examined supplements as recommended by producers did not lead to exceeding the CAF safe limit of 400 mg per day. Additionally, the MEKC-based method allowed for detection and identification of vitamin B3 and B6 in all of the investigated supplement samples, which demonstrated that MEKC-based protocols may be an appropriate assays for simultaneous determination of CAF and vitamins.


Assuntos
Cafeína/análise , Cromatografia Capilar Eletrocinética Micelar/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Vitaminas/análise , Suplementos Nutricionais/análise , Escore Lod , Niacinamida/análise , Vitamina B 6/análise
9.
BMC Med Genet ; 20(1): 27, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704416

RESUMO

BACKGROUND: Myopia is one of most common eye diseases in the world and affects 1 in 4 Americans. It is a complex disease caused by both environmental and genetics effects; the genetics effects are still not well understood. In this study, we performed genetic linkage analyses on Ashkenazi Jewish families with a strong familial history of myopia to elucidate any potential causal genes. METHODS: Sixty-four extended Ashkenazi Jewish families were previously collected from New Jersey. Genotypes from the Illumina ExomePlus array were merged with prior microsatellite linkage data from these families. Additional custom markers were added for candidate regions reported in literature for myopia or refractive error. Myopia was defined as mean spherical equivalent (MSE) of -1D or worse and parametric two-point linkage analyses (using TwoPointLods) and multi-point linkage analyses (using SimWalk2) were performed as well as collapsed haplotype pattern (CHP) analysis in SEQLinkage and association analyses performed with FBAT and rv-TDT. RESULTS: Strongest evidence of linkage was on 1p36(two-point LOD = 4.47) a region previously linked to refractive error (MYP14) but not myopia. Another genome-wide significant locus was found on 8q24.22 with a maximum two-point LOD score of 3.75. CHP analysis also detected the signal on 1p36, localized to the LINC00339 gene with a maximum HLOD of 3.47, as well as genome-wide significant signals on 7q36.1 and 11p15, which overlaps with the MYP7 locus. CONCLUSIONS: We identified 2 novel linkage peaks for myopia on chromosomes 7 and 8 in these Ashkenazi Jewish families and replicated 2 more loci on chromosomes 1 and 11, one previously reported in refractive error but not myopia in these families and the other locus previously reported in the literature. Strong candidate genes have been identified within these linkage peaks in our families. Targeted sequencing in these regions will be necessary to definitively identify causal variants under these linkage peaks.


Assuntos
Cromossomos Humanos/genética , Técnicas de Genotipagem/métodos , Judeus/genética , Miopia/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 8/genética , Exoma , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Escore Lod , Masculino , Miopia/etnologia , Linhagem , RNA Longo não Codificante/genética
10.
Theor Appl Genet ; 132(4): 1159-1177, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30569367

RESUMO

Loose cluster architecture is an important aim in grapevine breeding since it has high impact on the phytosanitary status of grapes. This investigation analyzed the contributions of individual cluster sub-traits to the overall trait of cluster architecture. Six sub-traits showed large impact on cluster architecture as major determinants. They explained 57% of the OIV204 descriptor for cluster compactness rating in a highly diverse cross-population of 149 genotypes. Genetic analysis revealed several genomic regions involved in the expression of this trait. Based on the linkage of phenotypic features to molecular markers, QTL calculations shed new light on the genetic determinants of cluster architecture. Eight QTL clusters harbor overlapping confidence intervals of up to four co-located QTLs. A physical projection of the QTL clusters by confidence interval-flanking markers onto the PN40024 reference genome sequence revealed genes enriched in these regions.


Assuntos
Genoma de Planta , Locos de Características Quantitativas/genética , Vitis/genética , Flores/genética , Genes de Plantas , Marcadores Genéticos , Escore Lod , Análise de Componente Principal , Característica Quantitativa Herdável
11.
Nat Commun ; 9(1): 5141, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510157

RESUMO

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.


Assuntos
Espessura Intima-Media Carotídea , Doença das Coronárias/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Placa Aterosclerótica/genética , Proteína ADAMTS9/genética , Aminoácido Oxirredutases/genética , Doença das Coronárias/patologia , Humanos , Escore Lod , Placa Aterosclerótica/patologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Fatores de Risco
12.
Am J Hum Genet ; 103(4): 568-578, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30290152

RESUMO

Infantile and childhood-onset cataracts form a heterogeneous group of disorders; among the many genetic causes, numerous pathogenic variants in additional genes associated with autosomal-recessive infantile cataracts remain to be discovered. We identified three consanguineous families affected by bilateral infantile cataracts. Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271∗) in large family F385 (nine affected individuals; LOD score = 5.18 at θ = 0), frameshift deletion c.2947_2948del (p.Asp983∗) in family F372 (two affected individuals), and frameshift variant c.2852_2855del (p.Thr951Metfs∗41) in family F3 (one affected individual). The phenotypes of all affected individuals include infantile-onset cataracts. RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells, and leads to a ∼50% reduction in electroretinography amplitudes in young flies. DNMBP regulates the shape of tight junctions, which correspond to the septate junctions in invertebrates, as well as the assembly pattern of E-cadherin in human epithelial cells. E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans. We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans.


Assuntos
Catarata/genética , Proteínas do Citoesqueleto/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Perda de Heterozigosidade/genética , Adulto , Alelos , Animais , Caderinas/genética , Criança , Drosophila/genética , Células Epiteliais/patologia , Exoma/genética , Feminino , Homozigoto , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Junções Íntimas/patologia
13.
Mol Psychiatry ; 23(12): 2254-2265, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29880880

RESUMO

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes.


Assuntos
Transtornos Mentais/genética , Análise de Sequência de DNA/métodos , Adulto , Alelos , Contactinas/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Família/psicologia , Feminino , Frequência do Gene/genética , Ligação Genética/genética , Predisposição Genética para Doença/genética , Testes Genéticos , Estudo de Associação Genômica Ampla , Genômica , Genótipo , Humanos , Escore Lod , Masculino , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Transtornos do Humor/genética , Herança Multifatorial , Proteínas do Tecido Nervoso/genética , Linhagem , Fenótipo , RNA Mensageiro/genética , Receptor de Glutamato Metabotrópico 5/genética , Proteínas Recombinantes de Fusão/genética , Translocação Genética
14.
J Genet ; 97(2): 391-398, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29932058

RESUMO

Hot water epilepsy (HWE) is a rare form of sensory epilepsy where seizures are precipitated by a stimulus of contact with hot water. While earlier studies have suggested causal role of genes for HWE, specific underpinnings are beginning to be explored only recently. We carried out a whole genome-based linkage analysis in a family where most of its members affected by HWE and found evidence of a previously unknown locus at chromosome 9p24.3-p23. Parametric two-point analysis suggested linkage with the greatest LOD score of 3.42 for the marker D9S286 at 9p24.1 at recombination fraction (θ) = 0, 90% penetrance value and 1% phenocopy rate. The highest multipoint LODscore of 3.42 was obtained for same marker at 9p24. The critical genetic interval of about 10 Mb of DNA was defined by the markers D9S917 and D9S168 corresponding to the centromere-distal and centromere-proximal recombination boundaries, respectively. This observation along with our previous findings of hot water genetic loci at 10q21.3-q22.3 (OMIM: 613339) and 4q24-q28 (OMIM: 613340), indicates unanticipated genetic heterogeneity for the disorder in families from a relatively small geographic region in the southern parts of India.


Assuntos
Cromossomos Humanos Par 9/genética , Epilepsia Parcial Sensorial/genética , Loci Gênicos/genética , Temperatura Alta/efeitos adversos , Água/efeitos adversos , Mapeamento Cromossômico , Epilepsia Parcial Sensorial/etiologia , Saúde da Família , Feminino , Predisposição Genética para Doença/genética , Humanos , Índia , Escore Lod , Masculino , Linhagem
15.
Gene ; 673: 211-216, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29933017

RESUMO

Incorrect paternity assignment in cattle can significantly influence the accuracy of genetic evaluation. Recent advances in high-throughput technology have facilitated the identification of single nucleotide polymorphism (SNP) markers and their applications for filiation and individual identification. We genotyped 1074 bulls from a reference population of Chinese Simmental cattle for genomic selection using a BovineSNP770K BeadChip. Among them, a total of 136 bulls were randomly selected to design a suitable low-density SNP panel for paternity testing in Simmental cattle. Our results showed that 50 SNPs were determined to be the most informative markers in parental testing, with an accuracy of 99.89% for CPE (cumulative probability of exclusion) in the unknown female parent case. The 50 highly informative SNP markers were distributed across 25 chromosomes, and the mean intermarker distance per chromosome was 26.72 Mb. The average minor allele frequency (MAF), expected heterozygosity (HE), and polymorphic information content (PIC) values were 0.3748, 0.4998, and 0.4818, respectively. Finally, the 50 identified SNPs were used to estimate paternity for the remaining 938 of 1074 bulls from 23 farms. Our results revealed that 76.75% of the 938 bulls were assigned parentage to the pedigree sires with 95% confidence, and the rate of pedigree record mistakes ranged from 9.52%-39.29% in different herds. Our study is the first attempt to provide valuable insights into the extraction of informative markers through the application of high-density SNP chips for paternity testing in Chinese Simmental cattle.


Assuntos
Testes Genéticos/veterinária , Polimorfismo de Nucleotídeo Único , Animais , Bovinos , China , Feminino , Frequência do Gene , Marcadores Genéticos , Genoma , Genótipo , Escore Lod , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Probabilidade
16.
BMC Oral Health ; 18(1): 98, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859070

RESUMO

BACKGROUND: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited. METHODS: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and (3) QTOT2: age-adjusted quantitative caries excluding pre-cavitated lesions. Genotyping was conducted for approximately 600,000 SNPs on an Illumina platform, pruned to 127,511 uncorrelated SNPs for the analyses reported here. RESULTS: Multipoint non-parametric linkage analyses generated peak LOD scores exceeding 2.0 for eight genomic regions, but no LOD scores above 3.0 were observed. The maximum LOD score for each of the three traits was 2.90 at 1q25.3 for PRIM, 2.38 at 6q25.3 for QTOT1, and 2.76 at 5q23.3 for QTOT2. Some overlap in linkage regions was observed among the phenotypes. Genes with a potential role in dental caries in the eight chromosomal regions include CACNA1E, LAMC2, ALMS1, STAMBP, GXYLT2, SLC12A2, MEGF10, TMEM181, ARID1B, and, as well as genes in several immune gene families. Our results are also concordant with previous findings from association analyses on chromosomes 11 and 19. CONCLUSIONS: These multipoint linkage results provide evidence in favor of novel chromosomal regions, while also supporting earlier association findings for these data. Understanding the genetic etiology of dental caries will allow designing personalized treatment plans based on an individual's genetic risk of disease.


Assuntos
Suscetibilidade à Cárie Dentária/genética , Cárie Dentária/genética , Adolescente , Adulto , Criança , Pré-Escolar , Cromossomos Humanos/genética , Estudo de Associação Genômica Ampla , Humanos , Iowa , Escore Lod , Pessoa de Meia-Idade , Pennsylvania , Fenótipo , Polimorfismo de Nucleotídeo Único , West Virginia , Adulto Jovem
17.
Genet Epidemiol ; 42(6): 500-515, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29862559

RESUMO

Multipoint linkage analysis is an important approach for localizing disease-associated loci in pedigrees. Linkage analysis, however, is sensitive to misspecification of marker allele frequencies. Pedigrees from recently admixed populations are particularly susceptible to this problem because of the challenge of accurately accounting for population structure. Therefore, increasing emphasis on use of multiethnic samples in genetic studies requires reevaluation of best practices, given data currently available. Typical strategies have been to compute allele frequencies from the sample, or to use marker allele frequencies determined by admixture proportions averaged over the entire sample. However, admixture proportions vary among pedigrees and throughout the genome in a family-specific manner. Here, we evaluate several approaches to model admixture in linkage analysis, providing different levels of detail about ancestral origin. To perform our evaluations, for specification of marker allele frequencies, we used data on 67 Caribbean Hispanic admixed families from the Alzheimer's Disease Sequencing Project. Our results show that choice of admixture model has an effect on the linkage analysis results. Variant-specific admixture proportions, computed for individual families, provide the most detailed regional admixture estimates, and, as such, are the most appropriate allele frequencies for linkage analysis. This likely decreases the number of false-positive results, and is straightforward to implement.


Assuntos
Doença de Alzheimer/genética , Pool Gênico , Hispano-Americanos/genética , Linhagem , Filogenia , Análise de Sequência de DNA , Região do Caribe , Grupos Étnicos , Família , Feminino , Frequência do Gene/genética , Ligação Genética , Genética Populacional , Humanos , Escore Lod , Masculino , Modelos Genéticos , Análise de Componente Principal
18.
Sci Rep ; 8(1): 6897, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720646

RESUMO

The acquisition of environmental osmolality tolerance traits in individuals and gametes is an important event in the evolution and diversification of organisms. Although teleost fish exhibit considerable intra- and interspecific variation in salinity tolerance, the genetic mechanisms underlying this trait remain unclear. Oryzias celebensis survives in sea and fresh water during both the embryonic and adult stages, whereas its close relative Oryzias woworae cannot survive in sea water at either stage. A linkage analysis using backcross progeny identified a single locus responsible for adult hyperosmotic tolerance on a fused chromosome that corresponds to O. latipes linkage groups (LGs) 6 and 23. Conversely, O. woworae eggs fertilised with O. celebensis sperm died in sea water at the cleavage stages, whereas O. celebensis eggs fertilised with O. woworae sperm developed normally, demonstrating that maternal factor(s) from O. celebensis are responsible for hyperosmotic tolerance during early development. A further linkage analysis using backcrossed females revealed a discrete single locus relating to the maternal hyperosmotic tolerance factor in a fused chromosomal region homologous to O. latipes LGs 17 and 19. These results indicate that a maternal factor governs embryonic hyperosmotic tolerance and maps to a locus distinct from that associated with adult hyperosmotic tolerance.


Assuntos
Adaptação Biológica , Oryzias/fisiologia , Pressão Osmótica , Locos de Características Quantitativas , Característica Quantitativa Herdável , Animais , Mapeamento Cromossômico , Cromossomos , Estudos de Associação Genética , Ligação Genética , Escore Lod , Oryzias/classificação
19.
BMC Plant Biol ; 18(1): 72, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29699487

RESUMO

BACKGROUND: Parthenocarpy is a desired trait in tomato because it can overcome problems with fruit setting under unfavorable environmental conditions. A parthenocarpic tomato cultivar, 'MPK-1', with a parthenocarpic gene, Pat-k, exhibits stable parthenocarpy that produces few seeds. Because 'MPK-1' produces few seeds, seedlings are propagated inefficiently via cuttings. It was reported that Pat-k is located on chromosome 1. However, the gene had not been isolated and the relationship between the parthenocarpy and low seed set in 'MPK-1' remained unclear. In this study, we isolated Pat-k to clarify the relationship between parthenocarpy and low seed set in 'MPK-1'. RESULTS: Using quantitative trait locus (QTL) analysis for parthenocarpy and seed production, we detected a major QTL for each trait on nearly the same region of the Pat-k locus on chromosome 1. To isolate Pat-k, we performed fine mapping using an F4 population following the cross between a non-parthenocarpic cultivar, 'Micro-Tom' and 'MPK-1'. The results showed that Pat-k was located in the 529 kb interval between two markers, where 60 genes exist. By using data from a whole genome re-sequencing and genome sequence analysis of 'MPK-1', we could identify that the SlAGAMOUS-LIKE 6 (SlAGL6) gene of 'MPK-1' was mutated by a retrotransposon insertion. The transcript level of SlAGL6 was significantly lower in ovaries of 'MPK-1' than a non-parthenocarpic cultivar. From these results, we could conclude that Pat-k is SlAGL6, and its down-regulation in 'MPK-1' causes parthenocarpy and low seed set. In addition, we observed abnormal micropyles only in plants homozygous for the 'MPK-1' allele at the Pat-k/SlAGL6 locus. This result suggests that Pat-k/SlAGL6 is also related to ovule formation and that the low seed set in 'MPK-1' is likely caused by abnormal ovule formation through down-regulation of Pat-k/SlAGL6. CONCLUSIONS: Pat-k is identical to SlAGL6, and its down-regulation causes parthenocarpy and low seed set in 'MPK-1'. Moreover, down-regulation of Pat-k/SlAGL6 could cause abnormal ovule formation, leading to a reduction in the number of seeds.


Assuntos
Frutas/genética , Genes de Plantas/genética , Lycopersicon esculentum/genética , Partenogênese/genética , Mapeamento Cromossômico , Flores/crescimento & desenvolvimento , Flores/ultraestrutura , Frutas/crescimento & desenvolvimento , Genes de Plantas/fisiologia , Genoma de Planta/genética , Escore Lod , Lycopersicon esculentum/crescimento & desenvolvimento , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Sementes/crescimento & desenvolvimento , Análise de Sequência de DNA
20.
J Hum Genet ; 63(7): 821-829, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29670293

RESUMO

MODY 5 and 6 have been shown to be low-penetrant MODYs. As the genetic background of unknown MODY is assumed to be similar, a new analytical strategy is applied here to elucidate genetic predispositions to unknown MODY. We examined to find whether there are major MODY gene loci remaining to be identified using SNP linkage analysis in Japanese. Whole-exome sequencing was performed with seven families with typical MODY. Candidates for novel MODY genes were examined combined with in silico network analysis. Some peaks were found only in either parametric or non-parametric analysis; however, none of these peaks showed a LOD score greater than 3.7, which is approved to be the significance threshold of evidence for linkage. Exome sequencing revealed that three mutated genes were common among 3 families and 42 mutated genes were common in two families. Only one of these genes, MYO5A, having rare amino acid mutations p.R849Q and p.V1601G, was involved in the biological network of known MODY genes through the intermediary of the INS. Although only one promising candidate gene, MYO5A, was identified, no novel, high penetrant MODY genes might remain to be found in Japanese MODY.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Mutação , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , Adolescente , Adulto , Sequência de Bases , Criança , Mapeamento Cromossômico , Diabetes Mellitus Tipo 2/diagnóstico , Exoma , Feminino , Expressão Gênica , Redes Reguladoras de Genes , Ligação Genética , Humanos , Japão/epidemiologia , Escore Lod , Masculino , Linhagem , Penetrância
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