5 research outputs found
Genetic basis of quantitative traits in chilli (Capsicum annuum L.) multi-parent populations based on skewness and kurtosis: Genetic basis of quantitative traits in chilli
No full textThe effectiveness of breeding and hence rate of genetic gain in chilli relies on understanding the genetics of target traits. Skewness and kurtosis, the third- and fourth-degree statistics, respectively, provide powerful tools to detect and characterize epistasis and the number of genes controlling traits. This study analyzed the genetics of three quantitative traits—average fruit weight (AFW), fruits plant⁻¹ (FP), and green fruit yield plant⁻¹ (GFY) - in 10 multi-parent (MP)-derived populations. Symmetrical platykurtic distributions in most MP populations indicated the predominance of numerous non-epistatic genes governing AFW, FP, and GFY, suggesting slow genetic gains with mild selection but rapid gains under intense selection. On contrary, positively skewed distributions in three MP populations indicated complementary epistatic genes with decreasing effects on FP and GFY. Additionally, leptokurtic distributions in two MPs indicated fewer genes controlling AFW and GFY, suggesting even mild selection is likely to be effective to improve these traits
Severe neurodevelopmental disease caused by a homozygous TLK2 variant
No full text\ua9 2019, The Author(s).A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described. All cases reported carried either truncating variants located throughout the gene, or missense changes principally located at the C-terminal end of the protein mostly resulting in haploinsufficiency of TLK2. Through whole exome sequencing, we identified a homozygous missense variant in TLK2 in a patient showing more severe symptoms than those previously described, including cerebellar vermis hypoplasia and West syndrome. Both parents are heterozygous for the variant and clinically unaffected highlighting that recessive variants in TLK2 can also be disease causing and may act through a different pathomechanism
Autosomal recessive variants in <em>TUBGCP2</em> alter the γ-tubulin ring complex leading to neurodevelopmental disease
No full text\ua9 2020 The Author(s). Microtubules help building the cytoskeleton of neurons and other cells. Several components of the gamma-tubulin (γ-tubulin) complex have been previously reported in human neurodevelopmental diseases. We describe two siblings from a consanguineous Turkish family with dysmorphic features, developmental delay, brain malformation, and epilepsy carrying a homozygous mutation (p.Glu311Lys) in TUBGCP2 encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans.\ua9 2020 The Author(s)Biological Sciences; Neuroscience; Molecular Neuroscience; Clinical Neuroscience; Systems Biology; Protemic
Author Correction: Perception, performance, and detectability of conversational artificial intelligence across 32 university courses
No full textCongenital myasthenic syndrome with mild intellectual disability caused by a recurrent SLC25A1 variant
No full text\ua9 2019, The Author(s). Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of disorders caused by mutations which lead to impaired neuromuscular transmission. SLC25A1 encodes a mitochondrial citrate carrier, associated mainly with the severe neurometabolic disease combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). We previously reported a single family with a homozygous missense variant in SLC25A1 with a phenotype restricted to relatively mild CMS with intellectual disability, but to date no additional cases of this CMS subtype had been reported. Here, we performed whole exome sequencing (WES) in three additional and unrelated families presenting with CMS and mild intellectual disability to identify the underlying causative gene. The WES analysis revealed the presence of a homozygous c.740G>A; p.(Arg247Gln) missense SLC25A1 variant, the same SLC25A1 variant as identified in the original family with this phenotype. Electron microscopy of muscle from two cases revealed enlarged and accumulated mitochondria. Haplotype analysis performed in two unrelated families suggested that this variant is a result of recurrent mutation and not a founder effect. This suggests that p.(Arg247Gln) is associated with a relatively mild CMS phenotype with subtle mitochondrial abnormalities, while other variants in this gene cause more severe neurometabolic disease. In conclusion, the p.(Arg247Gln) SLC25A1 variant should be considered in patients presenting with a presynaptic CMS phenotype, particularly with accompanying intellectual disability
