Anti-ASGR1 (aa 25-241) polyclonal antibody

The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a. genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO.

Purpose of reviewHuman genetics has provided new insights into the role of protein glycosylation in regulating lipoprotein metabolism. Here we review these new developments and discuss the biological insights they provide.Recent findingsCase descriptions of patients with congenital defects in N-glycosylation (CDG-I) frequently describe a distinct hypocholesterolemia in these rare multisystem clinical syndromes. Two novel CDGs with disturbed Golgi homeostasis and trafficking defects result in mixed glycosylation disorders, hepatic steatosis and hypercholesterolemia. In addition, the presence of particular N-glycans is essential for physiological membrane expression of scavenger receptor B1 and for adequate lipolytic activity of endothelial lipase. GalNAc-T2, a specific O-glycosyl transferase, was found to be a direct modulator of HDL metabolism across mammals, validating its relationship with HDL-c found in genome-wide association studies. Furthermore, genetic variation in ASGR1, the major subunit of the asialoglycoprotein receptor (ASGPR), was found to be associated with a reduction in LDL-c and risk of coronary artery disease.SummaryProtein glycosylation plays an important regulatory role in lipoprotein metabolism. Greater insight into how protein glycosylation regulates lipoprotein metabolism could provide novel approaches for the treatment of dyslipidemia.