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PloS One 2022Otosclerosis (OTSC) is the primary form of conductive hearing loss characterized by abnormal bone remodelling within the otic capsule of the human middle ear. A genetic... (Meta-Analysis)
Meta-Analysis
Otosclerosis (OTSC) is the primary form of conductive hearing loss characterized by abnormal bone remodelling within the otic capsule of the human middle ear. A genetic association of the RELN SNP rs3914132 with OTSC has been identified in European population. Previously, we showed a trend towards association of this polymorphism with OTSC and identified a rare variant rs74503667 in a familial case. Here, we genotyped these variants in an Indian cohort composed of 254 OTSC cases and 262 controls. We detected a significant association of rs3914132 with OTSC (OR = 0.569, 95%CI = 0.386-0.838, p = 0.0041). To confirm this finding, we completed a meta-analysis which revealed a significant association of the rs3914132 polymorphism with OTSC (Z = 6.707, p<0.0001) across different ethnic populations. Linkage analysis found the evidence of linkage at RELN locus (LOD score 2.1059) in the OTSC family which has shown the transmission of rare variant rs74503667 in the affected individuals. To understand the role of RELN and its receptors in the development of OTSC, we went further to perform a functional analysis of RELN/reelin. Here we detected a reduced RELN (p = 0.0068) and VLDLR (p = 0.0348) mRNA levels in the otosclerotic stapes tissues. Furthermore, a reduced reelin protein expression by immunohistochemistry was confirmed in the otosclerotic tissues. Electrophoretic mobility shift assays for rs3914132 and rs74503667 variants revealed an altered binding of transcription factors in the mutated sequences which indicates the regulatory role of these variations in the RELN gene regulation. Subsequently, we showed by scanning electron microscopy a change in stapes bone morphology of otosclerotic patients. In conclusion, this study evidenced that the rare variation rs74503667 and the common polymorphism rs3914132 in the RELN gene and its reduced expressions that were associated with OTSC.
Topics: Genetic Predisposition to Disease; Genotype; Humans; Otosclerosis; Polymorphism, Single Nucleotide; Reelin Protein
PubMed: 35658052
DOI: 10.1371/journal.pone.0269558 -
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 -
Journal of Affective Disorders Aug 2022The etiology of bipolar disorder (BD) is poorly understood. Considering the complexity of BD, pedigree-based sequencing studies focusing on haplotypes at specific loci...
BACKGROUND
The etiology of bipolar disorder (BD) is poorly understood. Considering the complexity of BD, pedigree-based sequencing studies focusing on haplotypes at specific loci may be practical to discover high-impact risk variants. This study comprehensively examined the haplotype sequence at 1p36-35 BD and recurrent depressive disorder (RDD) susceptibility loci.
METHODS
We surveyed BD families in Okinawa, Japan. We performed linkage analysis and determined the phased sequence of the affected haplotype using whole genome sequencing. We filtered rare missense variants on the haplotype. For validation, we conducted a case-control genetic association study on approximately 3000 Japanese subjects.
RESULTS
We identified a three-generation multiplex pedigree with BD and RDD. Strikingly, we identified a significant linkage with mood disorders (logarithm of odds [LOD] = 3.61) at 1p36-35, supported in other ancestry studies. Finally, we determined the entire sequence of the 6.4-Mb haplotype shared by all affected subjects. Moreover, we found a rare triplet of missense variants in the SPOCD1 gene on the haplotype. Notably, despite the rare frequency, one heterozygote with multiple SPOCD1 variants was identified in an independent set of 88 BD type I genotyping samples.
LIMITATIONS
The 1p36-35 sequence was obtained from only a single pedigree. The replicate sample was small. Short-read sequencing might miss structural variants. A polygenic risk score was not analyzed.
CONCLUSION
The 1p36-35 haplotype sequence may be valuable for future BD variant studies. In particular, SPOCD1 is a promising candidate gene and should be validated.
Topics: Bipolar Disorder; Chromosomes, Human, Pair 1; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; Humans; Mutation; Pedigree; Polymorphism, Single Nucleotide; Proteoglycans
PubMed: 35504398
DOI: 10.1016/j.jad.2022.04.150 -
The Science of the Total Environment Aug 2022Enantiomeric profiling can supplement wastewater-based epidemiology (WBE) by providing additional information on drug origin (licit or illicit), improving consumption...
Enantiomeric profiling can supplement wastewater-based epidemiology (WBE) by providing additional information on drug origin (licit or illicit), improving consumption estimates, i.e., differentiating between disposal and consumption, and offering an insight into the potency of drugs available on the illicit drug market. We report on the enantiomeric profiling of amphetamines in wastewater using R(-)-α-methoxy-α-(trifluoromethyl) phenylacetyl chloride (R-MTPCl), a chiral derivatising agent and GC-MS/MS. The method performed well when evaluated against the SANTE/12682/2019 guidelines in terms of recovery (81-99%), accuracy (99-111%), repeatability (1-8%RSD) and linearity (LOQ-1000 ng/mL). The LOD and LOQ were 120 ng/L and 400 ng/L, respectively. The method was applied to samples of raw wastewater from two Slovene municipalities with unusual levels of amphetamines: Ljubljana (LJ1) and Velenje (VE1). LJ1 had an anomalously high mass load of MDMA (3,4-methylenedioxymethamphetamine) identified during SCORE 2020, and VE1 is a representative sample of the consistently high mass load of amphetamine. A second Ljubljana sample (LJ2) was chosen as a representative sample. The presence of racemic MDMA (EF = 0.511) in LJ1 indicated the disposal of the unused drug into the sewer, while the enrichment of R-MDMA (EF = 0.666) in the combined extract sample from Ljubljana (LJ2) indicated consumption. In the case of Velenje and Ljubljana, it is impossible to distinguish between the direct disposal and consumption of amphetamine and methamphetamine. Also, since amphetamine/methamphetamine-based prescription medications are unavailable in Slovenia, racemic amphetamine in VE1 (EF = 0.514) and LJ2 (EF = 0.459) indicate racemic and the more potent S-amphetamine are sold on the illicit drug market. Only S-methamphetamine was detected in wastewater (LJ2: EF = 0), indicating the presence of only the more potent S-methamphetamine on the illicit drug market. Overall, enantiomeric profiling provided useful information on amphetamine residues. In addition, chiral derivatisation can be a cost-effective alternative to using chiral chromatographic columns for the enantiomeric profiling of amphetamines in wastewater.
Topics: Amphetamine; Amphetamines; Gas Chromatography-Mass Spectrometry; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Substance Abuse Detection; Tandem Mass Spectrometry; Wastewater; Water Pollutants, Chemical
PubMed: 35490814
DOI: 10.1016/j.scitotenv.2022.155594 -
Clinical Genetics Aug 2022Six individuals of consanguineous Bedouin kindred presented at infancy with an autosomal recessive syndrome of severe global developmental delay, positive pyramidal...
Six individuals of consanguineous Bedouin kindred presented at infancy with an autosomal recessive syndrome of severe global developmental delay, positive pyramidal signs, unique dysmorphism, skeletal abnormalities, and severe failure to thrive with normal birth weights. Patients had a profound intellectual disability and cognitive impairment with almost no acquired developmental milestones by 12 months. Early-onset axial hypotonia evolved with progressive muscle weakness, reduced muscle tone, and hyporeflexia. Craniofacial dysmorphism consisted of a triangular face with a prominent forehead and midface hypoplasia. Magnetic resonance imaging (MRI) demonstrated thinning of the corpus callosum and paucity of white matter. Genome-wide linkage analysis identified a single ~4 Mbp disease-associated locus on chromosome 7q21.13-q21.3 (LOD score>5). Whole-exome and genome sequencing identified no nonsynonymous pathogenic biallelic variants in any of the genes within this locus. Following the exclusion of partially resembling syndromes, we now describe a novel autosomal recessive syndrome mapped to a ~4Mbp locus on chromosome 7.
Topics: Chromosomes, Human, Pair 3; Corpus Callosum; Failure to Thrive; Humans; Intellectual Disability; Muscle Hypotonia; Syndrome
PubMed: 35443069
DOI: 10.1111/cge.14143 -
Turkish Journal of Obstetrics and... Mar 2022To investigate the impact of laparoscopic ovarian drilling (LOD) on the expression of endometrial NFκB p65 (Rel A) in women with clomiphene-resistant polycystic ovary...
OBJECTIVE
To investigate the impact of laparoscopic ovarian drilling (LOD) on the expression of endometrial NFκB p65 (Rel A) in women with clomiphene-resistant polycystic ovary syndrome (PCOS).
MATERIALS AND METHODS
The study group comprised 25 normal-weight women with PCOS undergoing LOD and 14 control women without PCOS. Endometrial NF-κB p65 levels evaluated before and after LOD following immunohistochemical staining. The semiquantitative method was used to evaluate the intensity of NF-κB p65 levels. NF-κB p65 was found to higher in the endometrium of patients with PCOS compared to controls. LOD leads to significant down-regulation in endometrial NF-κB p65 expression. NF-κB p65 expression of PCOS and fertile control were similar after LOD. After LOD, H-score values decreased approximately 3-fold. The H-score of the control subjects was lower than the preoperative and postoperative H-score values of the control women with ovarian cyst.
RESULTS
Expression of endometrial NF-κB p65 did not change following ovarian cystectomy. The laterality of the ovarian cyst did not cause any change in preoperative H-score values.
CONCLUSION
By downregulating the endometrial NF-κB p65 expression LOD improved physiological inflammation in women with PCOS.
PubMed: 35343219
DOI: 10.4274/tjod.galenos.2022.44845 -
Frontiers in Plant Science 2021An introgression breeding programme was carried out to transfer the virus resistance gene from the wild species to the garden asparagus . Serious crossing barriers...
An introgression breeding programme was carried out to transfer the virus resistance gene from the wild species to the garden asparagus . Serious crossing barriers caused by genetic distance and different ploidy levels of the crossing parents have been overcome using embryo rescue for the F, BC, and BC generations. The male and female fertility was widely restored in BC and was shown to be comparable to the cultivated asparagus. Five AV-1 resistant diploid (2n = 2x = 20) BC plants were selected and reciprocally backcrossed with asparagus cultivars. Segregation analyses of fourteen seedborne BC progenies suggested a monogenic dominant inheritance of the AV-1 resistance. Genotyping by sequencing analysis gave a strong hint for location of the resistance gene on asparagus Chromosome 2. Using an Axiom single nucleotide polymorphism (SNP) genotyping array for the analysis of three BC families with 10 AV-1 resistant and 10 AV-1 susceptible plants each, as well as 25 asparagus cultivars, the locus on Chromosome 2 was further narrowed down. The SNP with the highest LOD score was converted to a kompetitive allele specific PCR (KASP) marker, shown to be useful for the further backcross programme and serving as the starting point for the development of a diagnostic marker.
PubMed: 35251064
DOI: 10.3389/fpls.2021.809069 -
Frontiers in Plant Science 2021Bitter gourd ( L.) is an important vegetable crop having numerous medicinal properties. Earliness and yield related traits are main aims of bitter gourd breeding...
Bitter gourd ( L.) is an important vegetable crop having numerous medicinal properties. Earliness and yield related traits are main aims of bitter gourd breeding program. High resolution quantitative trait loci (QTLs) mapping can help in understanding the molecular basis of phenotypic variation of these traits and thus facilitate marker-assisted breeding. The aim of present study was to identify genetic loci controlling earliness, fruit, and seed related traits. To achieve this, genotyping-by-sequencing (GBS) approach was used to genotype 101 individuals of F population derived from a cross between an elite cultivar Punjab-14 and PAUBG-6. This population was phenotyped under net-house conditions for three years 2018, 2019, and 2021. The linkage map consisting of 15 linkage groups comprising 3,144 single nucleotide polymorphism (SNP) markers was used to detect the QTLs for nine traits. A total of 50 QTLs for these traits were detected which were distributed on 11 chromosomes. The QTLs explained 5.09-29.82% of the phenotypic variance. The highest logarithm of the odds (LOD) score for a single QTL was 8.68 and the lowest was 2.50. For the earliness related traits, a total of 22 QTLs were detected. For the fruit related traits, a total of 16 QTLs and for seed related traits, a total of 12 QTLs were detected. Out of 50 QTLs, 20 QTLs were considered as frequent QTLs (FQ-QTLs). The information generated in this study is very useful in the future for fine-mapping and marker-assisted selection for these traits in bitter gourd improvement program.
PubMed: 35211132
DOI: 10.3389/fpls.2021.799932 -
Brain Sciences Feb 2022(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether...
(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group ( < 0.05) but were not associated with any cognitive score in the LOD patients ( > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.
PubMed: 35204039
DOI: 10.3390/brainsci12020276 -
PloS One 2022All stage resistance to stripe rust races prevalent in India was investigated in the European winter wheat cultivar 'Acienda'. In order to dissect the genetic basis of...
All stage resistance to stripe rust races prevalent in India was investigated in the European winter wheat cultivar 'Acienda'. In order to dissect the genetic basis of the resistance, a backcross population was developed between 'Acienda' and the stripe rust susceptible Indian spring wheat cultivar 'HD 2967'. Inheritance studies revealed segregation for a dominant resistant gene. High density SNP genotyping was used to map stripe rust resistance and marker regression analysis located stripe rust resistance to the distal end of wheat chromosome 1A. Interval mapping located this region between the SNP markers AX-95162217 and AX-94540853, at a LOD score of 15.83 with a phenotypic contribution of 60%. This major stripe rust resistance locus from 'Acienda' has been temporarily designated as Yraci. A candidate gene search in the 2.76 Mb region carrying Yraci on chromosome 1A identified 18 NBS-LRR genes based on wheat RefSeqv1.0 annotations. Our results indicate that as there is no major gene reported in the Yraci chromosome region, it is likely to be a novel stripe rust resistance locus and offers potential for deployment, using the identified markers, to confer all stage stripe rust resistance.
Topics: Basidiomycota; Chromosome Mapping; Chromosomes, Plant; Disease Resistance; Gene Expression Regulation, Plant; India; Inheritance Patterns; Plant Diseases; Plant Proteins; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Seasons; Triticum
PubMed: 35171951
DOI: 10.1371/journal.pone.0264027