ABSTRACT
We report a single-point variant of low-density lipoprotein receptor (LDLR) in a Chinese proband with a clinical diagnosis of familial hypercholesterolemia (FH) with a comprehensive functional analysis. Target exome capture-based next-generation sequencing was used for sequencing and identification of genomic variants in the LDLR gene. The expression, cellular location, and function of the mutant LDLR were analyzed. Sequencing of LDLR in FH patients indicated a point variant of single-base substitution (G < A) at a position of 2389 in the 16th exon, which led to a loss of the 16th exon in the LDLR messenger RNA. This genomic variant was found to cause exon 16 deletion in the mutant LDLR protein. Subsequent functional analyses showed that the mutant LDLR was retained in the Golgi apparatus and rarely expressed in the cellular membranes of HepG2 cells. Accordingly, the intake ability of HepG2 cells with the mutant LDLR was significantly reduced (P < 0.05). In conclusion, our results suggest that a mutant with a single-base substitution (c. 2389G > A) in the 16th exon of the LDLR gene was associated with miscleavage of messenger RNA and the retention of mutant LDLR in the Golgi apparatus, which revealed a pathogenic variant in LDLR underlying the pathogenesis of FH.
ABSTRACT
Soil salinization and overgrazing are two main factors limiting animal husbandry in the Songnen Grassland. Leymus chinensis is a dominant rhizome grass, resistant to grazing as well as to-lerant to salt stress. Foliar labeled with 15N-urea was used to study the nitrogen allocation strategy and compensatory growth response to clipping under saline-alkali conditions. The results showed that the total absorbed 15N allocated to the aboveground part was more than 60%. Compared with the control treatment (no saline-alkali, no clipping), saline-alkali increased the distribution of 15N by 5.1% in root; the 15N distribution into aboveground in the moderate clipping and saline-alkali treatment was 11.6% higher than that of the control, exhibiting over-compensatory growth of aboveground biomass and total biomass, however, 15N allocated to stem base was significantly increased by 9.5% under severe clipping level and saline-alkali addition, showing under-compensatory growth of shoot, root and total biomass. These results suggested that L. chinensis adapted to mode-rate clipping by over-compensatory growth under salt-alkali stress condition. However, L. chinensis would take a relatively conservative growth strategy through the enhanced N allocation to stem base for storage under severe saline-alkali and clipping conditions.
