Abstract
Aim In IMGT/HLA Release 3.24.0, less than 7% of the named classical HLA alleles have curated full-length gene sequences or sequences outside the antigen recognition sites (ARS). This study is to investigate genetic variants, polymorphism, SNPs and linkage disequilibrium (LD) within the entire gene region for the classical HLA genes using information theory. Methods Multiple sequence alignment was performed on full-length HLA Class I alleles (HLA-A, -B, -C) and partial-length (from intron 1 through intron 3) Class II alleles (HLA-DQB1, -DRB1) for 15,865 subjects, followed by a gene annotation pipeline. We analyzed the Shannon entropy of each nucleotide site and mutual information within each of the loci. Conditional asymmetric linkage disequilibrium (ALD) measures were employed to characterize the LD between multiallelic SNPs within a locus. Results For HLA Class I alleles, the untranslated regions generally show high entropy variation. Highly variable sites (entropy >0.01) appear most in the noncoding regions (intron 3 in HLA-A and -B, respectively; intron 4 in HLA-C); while within coding regions, the ARS regions contain the most variants. However, since multiple sequence alignment introduces gaps that are ambiguous, we considered the distribution of variants after removing sites with at least one alignment gap. Consequently, for noncoding regions, intron 5 in HLA-A and -B, respectively, and introns 3 and 4 in HLA-C show the highest entropy variation; for coding regions, ARS regions remain highest entropy variation across all five loci. The ALD measures indicate that highly associated polymorphic sites mostly reside within exons 2, 3 and 4 (ARS regions for class II). Some of these associations also showed high heterogeneity. Conclusions Non-coding regions along with the non-ARS coding regions include many informative sites and the proposed method could be utilized in allele typing, typing validation, SNP association study, as well as matching for stem cell transplant.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
