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Development of Rheumatoid Arthritis Specific HLA-DRB1 Genotyping Microarray

Title
Development of Rheumatoid Arthritis Specific HLA-DRB1 Genotyping Microarray
Author
황승용
Keywords
Rheumatoid arthritis; HLA-DRB1; Oligonucleotide microarray; Genotyping; Risk allele; 4 digit; CYCLIC CITRULLINATED PEPTIDE; SHARED EPITOPE; SUSCEPTIBILITY; ASSOCIATION; POPULATION; ALLELES; HLA-DRB1-ASTERISK-0405; ANTIBODIES; PROTEINS; GENETICS
Issue Date
2014-09
Publisher
KOREAN BIOCHIP SOCIETY-KBCS, KOREA SCI & TECHNOL CENT, #310, 635-4, YEOGSAM-DONG, KANGNAM-GU, SEOUL, 135-703, SOUTH KOREA
Citation
BIOCHIP JOURNAL, 2014, 8(3), P.187-198
Abstract
HLA-DRB1 is the most important gene for rheumatoid arthritis (RA) susceptibility. The HLA-DRB1 shared epitope (SE) alleles that share conserved amino acid sequences and non-SE *09:01 allele account for about one-third of the genetic contribution to RA. We aimed to develop RA specific HLA-DRB1 genotyping microarray kit to achieve a 4-digit high resolution typing for the essential set of the susceptible DRB1 alleles in the RA. Korean RA patients (n=172) and controls (n=13) who performed BLA-DRB1 genotyping at 4-digit resolution by standard PCR-SBT method were enrolled. A total of 14 probes were designed for the RA specific HLA-DRB1 genotyping microarray. PCR products were hybridized with the probes which were covalently linked with a silylated glass slide of microarrays. BLA-DRB1 genotype was assigned using a signal table based on the scanned hybridization patterns. Using the RA-specific HLA-DRB I microarray chip, we accurately determined the RA susceptible alleles at 4-digit resolution (*01:01, *04:01, *04:04, *04: 05, *04:08, *04:10, *09:01, *10:10) and all the other subtypes of *04 in Korean population (n=185). Microarray results from 185 subjects showed high concordance with conventional PCR-SBT method irrespective of genotypes of risk or non-risk alleles (N=181), except for ambiguity in four cases of *01:01/*04:06 genotype, in which the microarray results were *01:01 /*04:03 or *01:01/*04:06. We developed a cost-effective RA-specific HLA-DRB1 genotyping microarray chip which is accurate and useful in clinical aspects as well as research purpose for RA.
URI
http://link.springer.com/article/10.1007%2Fs13206-014-8305-xhttp://hdl.handle.net/20.500.11754/52604
ISSN
1976-0280; 2092-7843
DOI
10.1007/s13206-014-8305-x
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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