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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 -
TAG. Theoretical and Applied Genetics.... May 2022A major gene controls flowering pattern in peanut, possibly encoding a TFL1-like. It was subjected to gain/loss events of a deletion and changes in mRNA expression...
A major gene controls flowering pattern in peanut, possibly encoding a TFL1-like. It was subjected to gain/loss events of a deletion and changes in mRNA expression levels, partly explaining the evolution of flowering pattern in Arachis. Flowering pattern (FP) is a major characteristic differentiating the two subspecies of cultivated peanut (Arachis hypogaea L.). Subsp. fastigiata possessing flowers on the mainstem (MSF) and a sequential FP, whereas subsp. hypogaea lacks MSF and exhibits an alternate FP. FP is considered the main contributor to plant adaptability, and evidence indicates that its diversification occurred during the several thousand years of domestication. However, the genetic mechanism that controls FP in peanut is unknown. We investigated the genetics of FP in a recombinant inbred population, derivatives of an A. hypogaea by A. fastigiata cross. Lines segregated 1:1 for FP, indicating a single gene effect. Using Axiom_Arachis2 SNP-array, FP was mapped to a small segment in chromosome B02, wherein a Terminal Flowering 1-like (AhTFL1) gene with a 1492 bp deletion was found in the fastigiata line, leading to a truncated protein. Remapping FP in the RIL population with the AhTFL1 indel as a marker increased the LOD score from 53.3 to 158.8 with no recombination in the RIL population. The same indel was found co-segregating with the phenotype in two independent EMS-mutagenized M2 families, suggesting a hotspot for gene conversion. Also, AhTFL1 was significantly less expressed in the fastigiata line compared to hypogaea and in flowering than non-flowering branches. Sequence analysis of the AhTFL1 in peanut world collections indicated significant conservation, supporting the putative role of AhTFL1 in peanut speciation during domestication and modern cultivation.
Topics: Arachis; Genome, Plant; INDEL Mutation; Phenotype
PubMed: 35260930
DOI: 10.1007/s00122-022-04068-1 -
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 -
Clinical Genetics Jul 2022Congenital anomalies of the kidney and urinary tract (CAKUT) are a spectrum of abnormalities affecting morphogenesis of the kidneys and other structures of the urinary...
Congenital anomalies of the kidney and urinary tract (CAKUT) are a spectrum of abnormalities affecting morphogenesis of the kidneys and other structures of the urinary tract. Bilateral renal agenesis (BRA) is the most severe presentation of CAKUT. Loss of either nephronectin (NPNT) or its receptor ITGA8 leads to failure of metanephric kidney development with resulting renal agenesis in murine models. Very recently, a single family with renal agenesis and a homozygous truncating variant in NPNT was reported. We report two families in whom genome-wide linkage analysis showed an autozygous locus linked to BRA (at least one member has unilateral renal agenesis) at 4q24, with an LOD score of ~3. Exome sequencing detected a nonsense variant in NPNT in both families within the linkage interval. The pathogenicity of this variant was supported by reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Our report confirms the candidacy of NPNT in renal agenesis in humans and shows that even complete loss of function can be compatible with the formation of a single kidney.
Topics: Animals; Congenital Abnormalities; Extracellular Matrix Proteins; Humans; Kidney; Kidney Diseases; Mice; Solitary Kidney; Urogenital Abnormalities; Vesico-Ureteral Reflux
PubMed: 35246978
DOI: 10.1111/cge.14128 -
Pakistan Journal of Pharmaceutical... Jan 2022Reported high performance liquid chromatographic (HPLC) methods for estimating metformin hydrochloride (MET) and sitagliptin phosphate monohydrate (SIT) are either...
Validation of a rapid and economical RP-HPLC method for simultaneous determination of metformin hydrochloride and sitagliptin phosphate monohydrate: Greenness evaluation using AGREE score.
Reported high performance liquid chromatographic (HPLC) methods for estimating metformin hydrochloride (MET) and sitagliptin phosphate monohydrate (SIT) are either laborious or contain higher proportions of organic solvents in mobile phase, thus presenting exorbitant procedures. So, a rapid, significantly more economical and eco-friendly HPLC method for synchronized analysis of both drugs was aimed to develop and validate in current study. Analytical evaluation was executed on Shimadzou⌖ C column (250mm × 4.6mm, 5μm) using acidified water and methanol 60:40 (v/v) as mobile phase at a flow of 1mL/min; while peaks were detected at 260nm at 25°C. Resultant values of accuracy, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), robustness and specificity depicted that the method was validated in accordance with the ICH Guidelines. The approximate retention time for MET and SIT were 1.96 and 3.70 min, correspondingly. The greenness score of the developed method was evaluated using AGREE software and was found better (0.81) as compared with the methods reported (<0.8). Conclusively, the developed method was time saving, economical, rapid, robust, rugged, precise, accurate and found to be applicable for simultaneous determination of MET and SIT in commercial tablets.
Topics: Chromatography, High Pressure Liquid; Green Chemistry Technology; Hypoglycemic Agents; Limit of Detection; Metformin; Reproducibility of Results; Sitagliptin Phosphate; Software
PubMed: 35221267
DOI: No ID Found -
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 -
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