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Genes Feb 2020Downy mildew (DM) is a major disease of maize that causes significant yield loss in subtropical and tropical regions around the world. A variety of DM strains have been...
Downy mildew (DM) is a major disease of maize that causes significant yield loss in subtropical and tropical regions around the world. A variety of DM strains have been reported, and the resistance to them is polygenically controlled. In this study, we analyzed the quantitative trait loci (QTLs) involved in resistance to (sorghum DM), (Java DM) (crazy top DM) using a recombinant inbred line (RIL) from a cross between B73 (susceptible) and Ki11 (resistant), and the candidate genes for , , and resistance were discovered. The linkage map was constructed with 234 simple sequence repeat (SSR) and restriction fragment length polymorphism (RFLP) markers, which was identified seven QTLs (chromosomes 2, 3, 6, and 9) for three DM strains. The major QTL, located on chromosome 2, consists of 12.95% of phenotypic variation explained (PVE) and a logarithm of odds (LOD) score of 14.12. Sixty-two candidate genes for , , and resistance were obtained between the flanked markers in the QTL regions. The relative expression level of candidate genes was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) using resistant (CML228, Ki3, and Ki11) and susceptible (B73 and CML270) genotypes. For the 62 candidate genes, 15 genes were upregulated in resistant genotypes. Among these, three (, , and ) and were annotated as leucine-rich repeat (LRR) and peroxidase (POX) genes, respectively. These candidate genes in the QTL regions provide valuable information for further studies related to , , and resistance.
Topics: Ascomycota; Chromosome Mapping; Chromosomes, Plant; Databases, Genetic; Disease Resistance; Gene Expression Regulation, Plant; Genetic Linkage; Microsatellite Repeats; Oomycetes; Peronospora; Peroxidase; Plant Diseases; Quantitative Trait Loci; Up-Regulation; Zea mays
PubMed: 32053973
DOI: 10.3390/genes11020191 -
Horticulture Research 2022The fresh and unique flavor of cucumber fruits, mainly composed of aldehydes and alcohols, is one of its most important fruit qualities. However, little is known about...
The fresh and unique flavor of cucumber fruits, mainly composed of aldehydes and alcohols, is one of its most important fruit qualities. However, little is known about the genetic basis of aroma compounds in cucumber fruit and the related quantitative trait loci (QTLs). In this study, genomic screening of QTLs underlying aroma compounds was performed based on the genetic linkage map constructed using 1301 single-nucleotide polymorphism (SNP) markers from genotyping-by-sequencing of a recombinant inbred line (RIL) population developed from Q16 × Q24. Significant genetic variations of aroma compounds in the RIL population were observed, and a total of 28 QTLs were screened. A major QTL () related to (,)-2,6-nonadien-1-ol was detected with a markedly high LOD score (10.97 in 2020 and 3.56 in 2019) between mk190 and mk204 on chromosome 2. Genome scans identified a cluster of nine lipoxygenase genes in this region. A significant positive correlation was detected between () and (,)-2,6-nonadien-1-ol, and five amino acid variations were detected between the CsLOX08 protein sequences of the two parental lines. Based on the genome variation of CsLOX08, we developed an InDel marker. Genotyping of InDel markers was consistent with the content of (,)-2,6-nonadien-1-ol in RILs, which were also verified in nine cucumber inbred lines. The results will give breeders guidance for obtaining better flavor in cucumber.
PubMed: 36196068
DOI: 10.1093/hr/uhac151 -
G3 (Bethesda, Md.) Dec 2023Hop production utilizes exclusively female plants, whereas male plants only serve to generate novel variation within breeding programs through crossing. Currently, hop...
Hop production utilizes exclusively female plants, whereas male plants only serve to generate novel variation within breeding programs through crossing. Currently, hop lacks a rapid and accurate diagnostic marker to determine whether plants are male or female. Without a diagnostic marker, breeding programs may take 1-2 years to determine the sex of new seedlings. Previous research on sex-linked markers was restricted to specific populations or breeding programs and therefore had limited transferability or suffered from low scalability. A large collection of 765 hop genotypes with known sex phenotypes, genotyping-by-sequencing, and genome-wide association mapping revealed a highly significant marker on the sex chromosome (LOD score = 208.7) that predicted sex within our population with 96.2% accuracy. In this study, we developed a PCR allele competitive extension (PACE) assay for the diagnostic SNP and tested three quick DNA extraction methodologies for rapid, high-throughput genotyping. Additionally, the marker was validated in a separate population of 94 individuals from 15 families from the USDA-ARS hop breeding program in Prosser, WA with 96% accuracy. This diagnostic marker is located in a gene predicted to encode the basic helix-loop-helix transcription factor protein, a family of proteins that have been previously implicated in male sterility in a variety of plant species, which may indicate a role in determining hop sex. The marker is diagnostic, accurate, affordable, and highly scalable and has the potential to improve efficiency in hop breeding.
Topics: Humans; Genome-Wide Association Study; Plant Breeding; Chromosome Mapping; Phenotype; Genotype
PubMed: 37963231
DOI: 10.1093/g3journal/jkad216 -
Addiction Neuroscience Dec 2022Impulsive behavior and impulsivity are heritable phenotypes that are strongly associated with risk for substance use disorders. Identifying the neurogenetic mechanisms...
Impulsive behavior and impulsivity are heritable phenotypes that are strongly associated with risk for substance use disorders. Identifying the neurogenetic mechanisms that influence impulsivity may also reveal novel biological insights into addiction vulnerability. Our past studies using the BXD and Collaborative Cross (CC) recombinant inbred mouse panels have revealed that behavioral indicators of impulsivity measured in a reversal-learning task are heritable and are genetically correlated with aspects of intravenous cocaine self-administration. Genome-wide linkage studies in the BXD panel revealed a quantitative trait locus (QTL) on chromosome 10, but we expect to identify additional QTL by testing in a population with more genetic diversity. To this end, we turned to Diversity Outbred (DO) mice; 392 DO mice (156 males, 236 females) were phenotyped using the same reversal learning test utilized previously. Our primary indicator of impulsive responding, a measure that isolates the relative difficulty mice have with reaching performance criteria under reversal conditions, revealed a genome-wide significant QTL on chromosome 7 (max LOD score = 8.73, genome-wide corrected p<0.05). A measure of premature responding akin to that implemented in the 5-choice serial reaction time task yielded a suggestive QTL on chromosome 17 (max LOD score = 9.14, genome-wide corrected <0.1). Candidate genes were prioritized ( based upon expression QTL data we collected in DO and CC mice and analyses using publicly available gene expression and phenotype databases. These findings may advance understanding of the genetics that drive impulsive behavior and enhance risk for substance use disorders.
PubMed: 36714272
DOI: 10.1016/j.addicn.2022.100045 -
Journal of Medical Genetics Jul 2019A single variant in (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify...
BACKGROUND
A single variant in (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia.
METHODS
Three families, including 15 affected individuals with syndromic X-linked microphthalmia, underwent analyses including linkage analysis, exome sequencing and targeted gene sequencing. The consequences of two identified variants in were evaluated using quantitative PCR and RNAseq.
RESULTS
Genetic linkage analysis in family 1 supported a candidate region on Xq27-q28, which included . Exome sequencing identified a hemizygous polyadenylation signal (PAS) variant, chrX:153,195,397T>C, c.*43A>G, which segregated with the disease. Targeted sequencing of affected males from families 2 and 3 identified distinct PAS variants, chrX:g.153,195,401T>C, c.*39A>G and chrX:g.153,195,400T>C, c.*40A>G. All three variants were absent from gnomAD. Quantitative PCR and RNAseq showed reduced mRNA levels and abnormal 3' UTRs in affected individuals. Targeted sequencing of in 376 additional affected individuals failed to identify variants in the PAS.
CONCLUSION
These data show that PAS variants are the most common variant type in -associated syndromic microphthalmia, suggesting reduced RNA is the molecular mechanism by which these alterations cause microphthalmia/anophthalmia. We reviewed recognised variants in PAS associated with Mendelian disorders and identified only 23 others, indicating that harbours more than 10% of all known PAS variants. We hypothesise that PAS in other genes harbour unrecognised pathogenic variants associated with Mendelian disorders. The systematic interrogation of PAS could improve genetic testing yields.
Topics: 3' Untranslated Regions; Alleles; Anophthalmos; Female; Genes, X-Linked; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Lod Score; Male; Microphthalmos; N-Terminal Acetyltransferase A; N-Terminal Acetyltransferase E; Pedigree; Poly A; Sequence Analysis, DNA; X Chromosome Inactivation
PubMed: 30842225
DOI: 10.1136/jmedgenet-2018-105836 -
Scientific Reports Jan 2022To compare the performance of high-sensitivity cardiac troponin I and T (hs-cTnI; hs-cTnT) in diagnosing obstructive coronary artery disease (CAD) in patients with...
To compare the performance of high-sensitivity cardiac troponin I and T (hs-cTnI; hs-cTnT) in diagnosing obstructive coronary artery disease (CAD) in patients with suspected chronic coronary syndrome (CCS). A total of 706 patients with suspected CCS, referred for Coronary Computed Tomography Angiography, were included. cTn concentrations were measured using the Singulex hs-cTnI (limit of detection [LoD] 0.08 ng/L) and Roche hs-cTnT (LoD 3 ng/L) assays. Obstructive coronary artery disease (CAD) was defined as ≥ 50% coronary stenosis. Cardiovascular risk was determined by the NORRISK2-score. Median age of the patients was 65 (range 28-87) years, 35% were women. All patients had hs-cTnI concentrations above the LoD (median 1.9 [Q1-3 1.2-3.6] ng/L), 72% had hs-cTnT above the LoD (median 5 [Q1-3 2-11] ng/L). There was a graded relationship between hs-cTn concentrations and coronary artery calcium. Only hs-cTnI remained associated with CAD in adjusted analyses (OR 1.20 95% Confidence Interval [1.05-1.38]), p = 0.009). The C-statistics for hs-cTnI and hs-cTnT were 0.65 (95% CI [0.60-0.69]) and 0.60 (0.56-0.64). The highest specificity and negative predictive values for CAD were in the lowest NORRISK2-tertile. hs-cTn concentrations provide diagnostic information in patients with suspected CCS, with superior performance of hs-cTnI compared to hs-cTnT in regard to CAD. The diagnostic performance appeared best in those with low cardiovascular risk.
Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Biomarkers; Computed Tomography Angiography; Coronary Artery Disease; Coronary Vessels; Female; Heart; Humans; Limit of Detection; Male; Middle Aged; Norway; Predictive Value of Tests; Troponin I; Troponin T
PubMed: 35042885
DOI: 10.1038/s41598-022-04850-7 -
Indian Journal of Ophthalmology Jun 2023This case-control study aims to examine possible associations of VSX1 exon3 gene variants with the development of keratoconus (KC) in Malaysian patients.
PURPOSE
This case-control study aims to examine possible associations of VSX1 exon3 gene variants with the development of keratoconus (KC) in Malaysian patients.
METHODS
A case-control study was done on 42 keratoconus cases, 127 family member controls, and 96 normal controls.
RESULTS
Three gene variants, p.A182A, p.P237P, and p.R217H showed significant associations with keratoconus (P < 0.05). While p.A182A and p.P227P were more prevalent than in the family and normal controls (OR 3.14-4.05), the reverse was observed with p.R217H (OR 0.086-1.59). With Haploview analysis, p.A182A and p.P237P were shown to be in linkage disequilibrium (LD) (LOD (logarithm of the odds score) score of 2.0, r2 of 0.957, and 95% confidence interval (CI) of 0.96-1.00).
CONCLUSION
The study results suggest that the p.A182A and p.P237P variants could have contributed to the development of keratoconus in some Malaysians and that these two variants are likely to be co-inherited. In contrast, the p.R217H variant appeared to confer some protection against the development of keratoconus.
Topics: Humans; Asian People; Case-Control Studies; Eye Proteins; Homeodomain Proteins; Keratoconus
PubMed: 37322657
DOI: 10.4103/IJO.IJO_2894_22 -
Genetic Variation and Recurrent Haplotypes on Chromosome 6q23-25 Risk Locus in Familial Lung Cancer.Cancer Research Jun 2021Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains...
Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on nine of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 in families 42 and 44, 6q25.2-25.3 in families 47 and 59, and 6q24.2-25.1 in families 30, 33, and 35. Region-based logarithm of the odds scores and expression data identified the likely candidate genes for each haplotype overlap: at 6q25.3, at 6q26, and (6q24.1) and (6q24.2). Further annotation was used to zero in on potential risk variants in those genes. All four genes are good candidate genes for lung cancer risk, having been linked to either lung cancer specifically or other cancers. However, this is the first time any of these genes has been implicated in germline risk. Functional analysis of these four genes is planned for future work. SIGNIFICANCE: This study identifies four genes associated with lung cancer risk, which could help guide future lung cancer prevention and treatment approaches.
Topics: Biomarkers, Tumor; Chromosome Mapping; Chromosomes, Human, Pair 6; Female; Genetic Linkage; Genetic Predisposition to Disease; Genetic Variation; Genome, Human; Haplotypes; Humans; Lod Score; Lung Neoplasms; Male; Pedigree; Prognosis
PubMed: 33853833
DOI: 10.1158/0008-5472.CAN-20-3196 -
PloS One 2019Hypotrichosis simplex (HS) with and without woolly hair (WH) comprises a group of rare, monogenic disorders of hair loss. Patients present with a diffuse loss of scalp...
Hypotrichosis simplex (HS) with and without woolly hair (WH) comprises a group of rare, monogenic disorders of hair loss. Patients present with a diffuse loss of scalp and/or body hair, which usually begins in early childhood and progresses into adulthood. Some of the patients also show hair that is tightly curled. Approximately 10 genes for autosomal recessive and autosomal dominant forms of HS have been identified in the last decade, among them five genes for the dominant form. We collected blood and buccal samples from 17 individuals of a large British family with HS and WH. After having sequenced all known dominant genes for HS in this family without the identification of any disease causing mutation, we performed a genome-wide scan, using the HumanLinkage-24 BeadChip, followed by a classical linkage analysis; and whole exome-sequencing (WES). Evidence for linkage was found for a region on chromosome 4q35.1-q35.2 with a maximum LOD score of 3.61. WES led to the identification of a mutation in the gene SORBS2, encoding sorbin and SH3 domain containing 2. Unfortunately, we could not find an additional mutation in any other patient/family with HS; and in cell culture, we could not observe any difference between cloned wildtype and mutant SORBS2 using western blotting and immunofluorescence analyses. Therefore, at present, SORBS2 cannot be considered a definite disease gene for this phenotype. However, the locus on chromosome 4q is a robust and novel finding for hypotrichosis with woolly hair. Further fine mapping and sequencing efforts are therefore warranted in order to confirm SORBS2 as a plausible HS disease gene.
Topics: Alleles; Chromosome Mapping; Chromosomes, Human, Pair 4; Female; Genes, Dominant; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Humans; Hypotrichosis; Male; Mutation; Pedigree; Phenotype; Quantitative Trait Loci; United Kingdom; Whole Genome Sequencing
PubMed: 31790498
DOI: 10.1371/journal.pone.0225943 -
Computational and Structural... 2022Although methodologies and software packages for bulked segregant analysis (BSA) are well established, it is difficult to detect extremely over-dominant and small-effect...
Although methodologies and software packages for bulked segregant analysis (BSA) are well established, it is difficult to detect extremely over-dominant and small-effect genes for quantitative traits in F population. To address this issue, we proposed a combinatorial strategy to identify all types of quantitative trait loci (QTLs) using extreme phenotype individuals in F. To popularize this strategy, we developed an R software package dQTG.seq v1.0.1. It has some features not found in other BSA software packages: 1) new (dQTG-seq1 and dQTG-seq2) and existing (G', deltaSNP, Euclidean distance (ED), and SmoothLOD) methods are available to identify all types of QTLs in bi-parental segregation populations, one data file with two BSA and three QTL-mapping data formats was inputted, and two *.csv files and one figure were outputted; 2) main smoothing methods (AIC, Window size, and Block) have been incorporated into each of the above-mentioned methods; 3) the threshold value of LOD score for significant QTLs is determined by permutation experiments. To save running time, vroom function was used to read the dataset, and parallel operation was used to estimate parameters. In real data analyses, users should select a suitable initial value of window size, depending on the species, and appropriate smoothing methods to obtain the best result. dQTG-seq2 detects more known loci and genes for rice grain number per panicle than composite interval mapping (CIM) and inclusive CIM, especially extremely over-dominant and small-effect genes. A handbook for our software package (https://cran.r-project.org/web/packages/dQTG.seq/index.html) has been provided in the supplemental materials for the users' convenience.
PubMed: 35615028
DOI: 10.1016/j.csbj.2022.05.009