Biology subjects

Augusto, J.

Publications and source records attributed to Augusto, J..

2 recordsLinked to original sources

bioRxiv2021

Sexual dimorphism in epilepsy and comorbidities in Dravet syndrome mice carrying a targeted deletion of exon 1 of the Scn1a gene

ObjectiveDravet Syndrome (DS) is a catastrophic form of paediatric epilepsy associated with multiple comorbidities mainly caused by mutations in the SCN1A gene. DS progresses in three different phases termed febrile, worsening and stabilization stage. Mice that are haploinsufficient for Scn1a faithfully model each stage of DS, although various aspects have not been fully described, including the temporal appearance and sex differences of the epilepsy and comorbidities. The aim of the present study was to investigate the epilepsy landscape according to the progression of DS and the long-term co-morbidities in the Scn1a(+/-)tm1Kea DS mouse line that are not fully understood yet. MethodsMale and female F1.Scn1a(+/+) and F1.Scn1a(+/-)tm1Kea mice were assessed in the hyperthermia model or monitored by video electroencephalogram (vEEG) and wireless video-EEG according to the respective stage of DS. Long-term comorbidities were investigated through a battery of behaviour assessments in [~]6 month-old mice. ResultsAt P18, F1.Scn1a(+/-)tm1Kea mice showed the expected sensitivity to hyperthermia-induced seizures. Between P21 and P28, EEG recordings in F1.Scn1a(+/-)tm1Kea mice combined with video monitoring revealed a high frequency of SRS and SUDEP. Power spectral analyses of background EEG activity also revealed that low EEG power in multiple frequency bands was associated with SUDEP risk in F1.Scn1a(+/-)tm1Kea mice during the worsening stage of DS. Later, SRS and SUDEP rates stabilized and then declined in F1.Scn1a(+/-)tm1kea mice. SRS and SUDEP in F1.Scn1a(+/-)tm1kea mice displayed variations with the time of day and sex, with female mice displaying higher numbers of seizures and greater SUDEP risk. F1.Scn1a(+/-)tm1kea mice [~]6 month- old displayed fewer behavioural impairments than expected including hyperactivity, impaired exploratory behaviour and poor nest building performance. SignificanceThese results reveal new features of this model that will optimize use and selection of phenotype assays for future studies on the mechanisms, diagnosis, and treatment of DS. Key point boxO_LIScn1a(+/-)tm1kea DS mouse model faithfully reproduces the three stages of DS C_LIO_LISex of F1.Scn1a(+/-)tm1kea mice influences the epilepsy phenotype C_LIO_LIF1.Scn1a(+/-)tm1kea develop some of the long-term comorbidities of DS C_LI

neuroscience↗

bioRxiv2018

An EST-SSR based genetic linkage map and identification of QTLs for anthracnose disease resistance in water yam (Dioscorea alata L.)

Water yam (Dioscorea alata L.) is one of the most important food yams with wide geographical distribution in tropics. One of the major constraints to water yam production is anthracnose disease caused by a fungus, Colletotrichum gloesporioides (Penz.). There are no economically feasible solutions as chemical sprays or cultural practices, such as crop rotation are seldom convenient for smallholder farmers for sustainable control of the disease. Breeding for development of durable genetic resistant varieties is known to offer lasting solution to control endemic disease threats to crop production. However, breeding for resistance to anthracnose has been slow considering the biological constraints related to the heterozygous and vegetative propagation of the crop. The development of saturated linkage maps with high marker density, such as SSRs, followed by identification of QTLs can accelerate the speed and precision of resistance breeding in water yam. A total of 380 EST-SSRs were used to generate a saturated linkage map. About 60.19% of SSRs showed Mendelian segregation pattern, however, it had no effect on the construction of linkage map. All 380 EST-SSRs were mapped into 20 linkage groups covering a total length of 2559.66 cM, which agrees with the diploid nature (2n = 2x = 20) of the parents used in the cross. Majority of the markers were mapped on linkage group 1 comprising of 97 EST-SSRs. This is the first genetic linkage map of water yam constructed using EST-SSRs. QTL localization was based on phenotypic data collected over a 3-year period of inoculating the mapping population with the most virulent strain of C. gloeosporoides from West Africa. Using the mean permutation value of LOD scores as threshold value for declaring a putative QTL on all linkage groups, one QTL was consistently observed on linkage group (LG) 14 in all the three years and average score data. This QTL was found at position interval of 71.12 - 84.76 cM explaining 68.94% of the total phenotypic variation in the average score data. The high marker density allowed identification of QTLs and association for anthracnose disease, which could be validated in other mapping populations and used in marker-assisted breeding in D. alata improvement programmes.

molecular biology↗