Internal Dataset
Rare Variants and HLA Haplotypes Associated in Serbian Patients with Neuromyelitis Optica Spectrum Disorders
UID: 10418
- Description
- Neuromyelitis optica spectrum disorders (NMOSD) are rare, debilitating, antibody-mediated autoimmune diseases of the central nervous system. Prior studies show associations of NMOSD with individual Human Leukocyte Antigen (HLA) alleles and the complement pathway. HLA allele associations with NMOSD are inconsistent between populations, suggesting complex relationships between the identified alleles and disease risk. Other genetic components that may contribute to NMOSD have not been thoroughly investigated. To address these issues, we performed HLA sequencing on 26 NMO patients from Belgrade, Serbia, and exome sequencing on a total of 40 NMO patients: 26 from Belgrade and 14 additional patients from New York State. We analyzed NMOSD associations with HLA haplotypes and used in silico modeling to identify potential mechanisms by which these haplotypes could contribute to NMOSD. By analyzing exome sequencing data, we identified rare inherited variants as well as de novo variants that likely contribute to disease. Here we broaden the candidate pathways involved in the progression of NMOSD and propose a mechanism by which specific HLA alleles can lead to disease development. We thus provide a potential explanation for the inconsistent allele associations between populations. Our results point to possible autoimmune and neurodegenerative mechanisms that cause NMOSD and can be used to investigate potential NMOSD drug targets.
- Local Expert
Access
- Restrictions
-
Free to AllApplication Required
- Instructions
- The database of Genotypes and Phenotypes (dbGaP) was developed to archive and distribute the data and results from studies that have investigated the interaction of genotype and phenotype in Humans. Application required, see dbGaP instructions.
The BioProject database provides an organizational framework to access information about research projects with links to data that have been or will be deposited into archival databases maintained at members of the International Nucleotide Sequence Database Consortium.
- Grant Support
-
HF Langbert Neuroimmunology Research Fund/HF Langbert Neuroimmunology Research Fund
Do you have or know of a dataset that should be added to the catalog? Let us know!