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TAG. Theoretical and Applied Genetics.... Apr 2022A major QTL, qBWA12, was fine mapped to a 216.68 kb physical region, and A12.4097252 was identified as a useful KASP marker for breeding peanut varieties resistant to...
A major QTL, qBWA12, was fine mapped to a 216.68 kb physical region, and A12.4097252 was identified as a useful KASP marker for breeding peanut varieties resistant to bacterial wilt. Bacterial wilt, caused by Ralstonia solanacearum, is a major disease detrimental to peanut production in China. Breeding disease-resistant peanut varieties is the most economical and effective way to prevent the disease and yield loss. Fine mapping the QTLs for bacterial wilt resistance is critical for the marker-assisted breeding of disease-resistant varieties. A recombinant inbred population comprising 521 lines was used to construct a high-density genetic linkage map and to identify QTLs for bacterial wilt resistance following restriction-site-associated DNA sequencing. The genetic map, which included 5120 SNP markers, covered a length of 3179 cM with an average marker distance of 0.6 cM. Four QTLs for bacterial wilt resistance were mapped on four chromosomes. One major QTL, qBWA12, with LOD score of 32.8-66.0 and PVE of 31.2-44.8%, was stably detected in all four development stages investigated over the 3 trial years. Additionally, qBWA12 spanned a 2.7 cM region, corresponding to approximately 0.4 Mb and was fine mapped to a 216.7 kb region by applying KASP markers that were polymorphic between the two parents based on whole-genome resequencing data. In a large collection of breeding and germplasm lines, it was proved that KASP marker A12.4097252 can be applied for the marker-assisted breeding to develop peanut varieties resistant to bacterial wilt. Of the 19 candidate genes in the region covered by qBWA12, nine NBS-LRR genes should be further investigated regarding their potential contribution to the resistance of peanut against bacterial wilt.
Topics: Arachis; Chromosome Mapping; Disease Resistance; Phenotype; Plant Breeding; Plant Diseases; Polymorphism, Single Nucleotide
PubMed: 35059781
DOI: 10.1007/s00122-022-04033-y -
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 -
Horticulture Research Jan 2022Free amino acids are one of the main chemical components in tea, and they contribute to the pleasant flavor, function, and quality of tea, notably the level of theanine....
Free amino acids are one of the main chemical components in tea, and they contribute to the pleasant flavor, function, and quality of tea, notably the level of theanine. Here, a high-density genetic map was constructed to characterize quantitative trait loci (QTLs) for free amino acid content. A total of 2688 polymorphic SNP markers were obtained using genotyping-by-sequencing (GBS) based on 198 individuals derived from a pseudotestcross population of "Longjing 43" × "Baijiguan", which are elite and albino tea cultivars, respectively. The 1846.32 cM high-density map with an average interval of 0.69 cM was successfully divided into 15 linkage groups (LGs) ranging from 93.41 cM to 171.28 cM. Furthermore, a total of 4 QTLs related to free amino acid content (theanine, glutamate, glutamine, aspartic acid and arginine) identified over two years were mapped to LG03, LG06, LG11 and LG14. The phenotypic variation explained by these QTLs ranged from 11.8% to 23.7%, with an LOD score from 3.56 to 7.7. Furthermore, several important amino acid metabolic pathways were enriched based on the upregulated differentially expressed genes (DEGs) among the offspring. These results will be essential for fine mapping genes involved in amino acid pathways and diversity, thereby providing a promising avenue for the genetic improvement of tea plants.
PubMed: 35040977
DOI: 10.1093/hr/uhab029 -
Journal of Translational Medicine Dec 2021Comitant strabismus (CS) is a heterogeneous disorder that is a major contributing factor to unilateral childhood-onset visual impairment. Studies have confirmed that...
BACKGROUND
Comitant strabismus (CS) is a heterogeneous disorder that is a major contributing factor to unilateral childhood-onset visual impairment. Studies have confirmed that genetic factors play an important role in the development of CS. The aim of this study was to identify the genetic cause of non-syndromic familial CS.
METHODS
Fourteen unrelated CS families were recruited for the study. Twelve affected and 2 unaffected individuals from a large four-generation family (CS08) were selected to perform whole genome-wide linkage analysis. Parallel whole-exome sequencing (WES) was conducted in the same family (9 patients and 1 unaffected member) and 31 additional CS cases from 13 other unrelated families. Sanger sequencing was used to determine whether any of the remaining variants co-segregated with the disease phenotype in the corresponding family.
RESULTS
Based on linkage analysis, CS in family CS08 mapped to a novel region of 34.17 centimorgan (cM) on chromosome 2q22.3-2q32.1 between markers D2S151 and D2S364, with a maximum log odds (LOD) score of 3.54 (theta = 0) at D2S142. Parallel WES identified a heterozygous variant, LRP2 c.335 A > G (p.Q112R), located in such a linkage interval that completely co-segregated with the disease in the family. Furthermore, another novel heterozygous variant (c.7274A > G, p.D2425G) in LRP2 that co-segregated was detected in 2 additional affected individuals from another unrelated family by WES. Both variants are predicted to be damaging by PolyPhen-2, SIFT and MutationTaster, and were absent in 100 ethnically matched normal controls.
CONCLUSION
LRP2 is a novel candidate genetic cause of non-syndromic familial CS.
Topics: Child; Heterozygote; Humans; Low Density Lipoprotein Receptor-Related Protein-2; Mutation; Pedigree; Strabismus; Exome Sequencing
PubMed: 34872573
DOI: 10.1186/s12967-021-03155-z -
Genome Mar 2022Fusarium wilt, caused by f. sp. , is the most destructive disease in castor. Host plant resistance is the best strategy for the management of wilt. Identification of...
Fusarium wilt, caused by f. sp. , is the most destructive disease in castor. Host plant resistance is the best strategy for the management of wilt. Identification of molecular markers linked to wilt resistance will enhance the efficiency and effectiveness of breeding for wilt resistance. In the present study, genomic regions linked to wilt resistance were mapped using a bi-parental population of 185 F-RILs and a genetically diverse panel of 300 germplasm accessions. Quantitative trait loci (QTL) analysis performed using a linkage map consisting of 1090 SNP markers identified a major QTL on chromosome 7 with an LOD score of 18.7, which explained 44% of the phenotypic variance. The association mapping performed using genotypic data from 3465 SNP loci revealed 69 significant associations ( < 1 × 10) for wilt resistance. The phenotypic variance explained by the individual SNPs ranged from 0.063 to 0.210. The QTL detected in the bi-parental mapping population was not identified in the association analysis. Thus, the results of this study indicate the possibility of vast gene diversity for Fusarium wilt resistance in castor.
Topics: Disease Resistance; Fusarium; Genetic Linkage; Genomics; Plant Diseases
PubMed: 34818083
DOI: 10.1139/gen-2020-0048 -
Breeding Science Jun 2021Smut disease of sugarcane causes considerable yield losses and the use of resistant varieties is the best control practice. Our group identified a Japanese wild...
Smut disease of sugarcane causes considerable yield losses and the use of resistant varieties is the best control practice. Our group identified a Japanese wild sugarcane with highly smut disease resistance named 'Iriomote8'. In this study, we conducted QTL analysis for smut disease resistance using a mapping population derived from a resistant variety 'Yaenoushie', in which resistance is inherited from 'Iriomote8'. We identified 4813 non-redundant markers using GRAS-Di technology and developed a linkage map of mapping parents. We evaluated smut disease resistance of the mapping population by the inoculation test. Consequently, a large number of clones did not show the disease symptoms and the distribution of smut disease incidence tended to be "L shaped". Composite interval mapping detected an identical QTL for indices of smut disease incidence with a markedly high LOD score (26.6~45.6) at the end of linkage group 8 of 'Yaenoushie'. This QTL explained approximately 50% of the cases of smut disease incidence. In the mapping population, there were no correlations between the indices of smut disease incidence and other agronomic traits. In conclusion, this QTL could be used for marker-assisted selection to significantly improve smut disease resistance without negative effects on other agronomic traits.
PubMed: 34776743
DOI: 10.1270/jsbbs.20137 -
Journal of Medical Genetics Sep 2022Auriculocondylar syndrome (ARCND) is a rare genetic disease that affects structures derived from the first and second pharyngeal arches, mainly resulting in micrognathia...
BACKGROUND
Auriculocondylar syndrome (ARCND) is a rare genetic disease that affects structures derived from the first and second pharyngeal arches, mainly resulting in micrognathia and auricular malformations. To date, pathogenic variants have been identified in three genes involved in the EDN1-DLX5/6 pathway (, and ) and some cases remain unsolved. Here we studied a large unsolved four-generation family.
METHODS
We performed linkage analysis, resequencing and Capture-C to investigate the causative variant of this family. To test the pathogenicity of the CNV found, we modelled the disease in patient craniofacial progenitor cells, including induced pluripotent cell (iPSC)-derived neural crest and mesenchymal cells.
RESULTS
This study highlights a fourth locus causative of ARCND, represented by a tandem duplication of 430 kb in a candidate region on chromosome 7 defined by linkage analysis. This duplication segregates with the disease in the family (LOD score=2.88) and includes , which is located over 200 kb telomeric to the top candidate gene . Notably, Capture-C analysis revealed multiple cis interactions between the promoter and possible regulatory elements within the duplicated region. Modelling of the disease revealed an increased expression of and its neighbouring gene, , in neural crest cells. We also identified decreased migration of iPSC-derived neural crest cells together with dysregulation of osteogenic differentiation in iPSC-affected mesenchymal stem cells.
CONCLUSION
Our findings support the hypothesis that the 430 kb duplication is causative of the ARCND phenotype in this family and that deregulation of expression during craniofacial development can contribute to the phenotype.
Topics: Ear; Ear Diseases; Humans; Nuclear Proteins; Osteogenesis; Regulatory Sequences, Nucleic Acid; Twist-Related Protein 1
PubMed: 34750192
DOI: 10.1136/jmedgenet-2021-107825 -
Current Biology : CB Dec 2021Many aspects of sleep are heritable, but only a few sleep-regulating genes have been reported. Here, we leverage mouse models to identify and confirm a previously...
Many aspects of sleep are heritable, but only a few sleep-regulating genes have been reported. Here, we leverage mouse models to identify and confirm a previously unreported gene affecting sleep duration-dihydropyrimidine dehydrogenase (Dpyd). Using activity patterns to quantify sleep in 325 Diversity Outbred (DO) mice-a population with high genetic and phenotypic heterogeneity-a linkage peak for total sleep in the active lights off period was identified on chromosome 3 (LOD score = 7.14). Mice with the PWK/PhJ ancestral haplotype at this location demonstrated markedly reduced sleep. Among the genes within the linkage region, available RNA sequencing data in an independent sample of DO mice supported a highly significant expression quantitative trait locus for Dpyd, wherein reduced expression was associated with the PWK/PhJ allele. Validation studies were performed using activity monitoring and EEG/EMG recording in Collaborative Cross mouse strains with and without the PWK/PhJ haplotype at this location, as well as EEG and EMG recording of sleep and wake in Dpyd knockout mice and wild-type littermate controls. Mice lacking Dpyd had 78.4 min less sleep during the lights-off period than wild-type mice (p = 0.007; Cohen's d = -0.94). There was no difference in other measured behaviors in knockout mice, including assays evaluating cognitive-, social-, and affective-disorder-related behaviors. Dpyd encodes the rate-limiting enzyme in the metabolic pathway that catabolizes uracil and thymidine to β-alanine, an inhibitory neurotransmitter. Thus, data support β-alanine as a neurotransmitter that promotes sleep in mice.
Topics: Animals; Dihydrouracil Dehydrogenase (NADP); Haplotypes; Mice; Mice, Knockout; Sleep; beta-Alanine
PubMed: 34653361
DOI: 10.1016/j.cub.2021.09.049 -
Nature Communications Sep 2021Evolutionary constraints may significantly bias phenotypic change, while "breaking" from such constraints can lead to expanded ecological opportunity. Ray-finned fishes...
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.
Topics: Animals; Biological Evolution; Cichlids; Ecosystem; Feeding Behavior; Female; Jaw; Lod Score; Male; Mouth; Pharynx; Quantitative Trait Loci; Sequence Analysis, DNA; X-Ray Microtomography
PubMed: 34531386
DOI: 10.1038/s41467-021-25755-5 -
Archives of Sexual Behavior Nov 2021Male sexual orientation is influenced by environmental and complex genetic factors. Childhood gender nonconformity (CGN) is one of the strongest correlates of...
Male sexual orientation is influenced by environmental and complex genetic factors. Childhood gender nonconformity (CGN) is one of the strongest correlates of homosexuality with substantial familiality. We studied brothers in families with two or more homosexual brothers (409 concordant sibling pairs in 384 families, as well as their heterosexual brothers), who self-recalled their CGN. To map loci for CGN, we conducted a genome-wide linkage scan (GWLS) using SNP genotypes. The strongest linkage peaks, each with significant or suggestive two-point LOD scores and multipoint LOD score support, were on chromosomes 5q31 (maximum two-point LOD = 4.45), 6q12 (maximum two-point LOD = 3.64), 7q33 (maximum two-point LOD = 3.09), and 8q24 (maximum two-point LOD = 3.67), with the latter not overlapping with previously reported strongest linkage region for male sexual orientation on pericentromeric chromosome 8. Family-based association analyses were used to identify associated variants in the linkage regions, with a cluster of SNPs (minimum association p = 1.3 × 10) found at the 5q31 linkage peak. Genome-wide, clusters of multiple SNPs in the 10 to 10 p-value range were found at chromosomes 5p13, 5q31, 7q32, 8p22, and 10q23, highlighting glutamate-related genes. This is the first reported GWLS and genome-wide association study on CGN. Further increasing genetic knowledge about CGN and its relationships to male sexual orientation should help advance our understanding of the biology of these associated traits.
Topics: Gender Identity; Genetic Linkage; Genome-Wide Association Study; Heterosexuality; Homosexuality, Male; Humans; Male; Siblings
PubMed: 34518958
DOI: 10.1007/s10508-021-02146-x