This study identified a novel HLA-A allele, HLA-A*01:195, in a UAE national. Sequencing analysis revealed a single nucleotide polymorphism (SNP) that results in an amino acid substitution - a valine instead of an isoleucine at position 124 of the alpha 1 chain of the HLA-A protein. Prediction tools indicate this mutation is likely intolerant and may impact the structure and function of the HLA-A protein. The allele was officially named HLA-A*01:195 by the WHO Nomenclature Committee and submitted to genetic databases. This finding provides new insights into genetic variations in the UAE population.

1. Wael Abdraboua, Ini-Isabée Witzela, Agnieszka Paduchb, Guan Tayc and Habiba Alsafard
aDepartment of Biomedical Engineering, Khalifa University of Science, Technology & Research, Abu Dhabi, UAE
bTransplant Diagnostics, Thermo Fisher Scientific, Hennigsdorf, Germany
cCentre for Forensic Science, University of Western Australia, Crawley, Western Australia
dKhalifa University Center of Excellence in Biotechnology, Khalifa University of Science, Technology & Research, Abu Dhabi, UAE
Identification of a Novel HLA-A allele,
HLA-A*01:195, in a UAE National

2. OBJECTIVES & BACKGROUND
Major Histocompatibility Complex (MHC):
• A set of cell surface molecules.
• Encoded by a large gene family that determines
histocompatibility in all vertebrates.
The Human Leukocyte Antigen (HLA):
• The most polymorphic genes in human genome.
HLA Class I Genes: (HLA-A, B and C)
• They encode glycoproteins that present antigens to T
lymphocytes to trigger the immune responses.
• Exons 2 and 3 of HLA class I encode the α1 and α2
domains that form the peptide-binding grove, and
are highly polymorphic.
Figure 3: HLA Complex
Figure 3: HLA Genes (Classes I, II & III)
STUDY OUTCOME
A novel variant of the HLA-A*01 allele was discovered, while
conducting a study of the MHC complex through high resolution
genotyping of HLA alleles to provide new insights into the genetics
of the United Arab Emirates population and mutations that may
predispose to autoimmune disease or play important role in
matching donors and recipients for transplants of hematopoietic
stem cells and solid organs.
2

3. MATERIALS AND METHODS

4. RESULTS: Sequencing Analysis
Figure 3: Matching the Novel allele to the closest identified matches
HLA-A*Novel
HLA-A*03:01:01:01
1. Initial DNA Sequence.
2. A confirmatory run.
3. HLA-A*03:01:01:01
(identified using Z5 SeCore GSSP)
4. HLA-A*Novel
(identified using Z6 SeCore GSSP)
 An alignment of 4 DNA sequences indicating the novel heterozygous site:
1
2
3
4
Figure 4: Alignment of the protein and nucleotide sequences for the common HLA*01:01:01:01 and novel HLA-A*01:195 allele.

5. HLA-A Exon 3
Nucleotide 442
ATC GTC
α1 chain
Codon 124
Isoleucine
(Ile)
Valine
(Val)
Closest WT Match:
• HLA-A*01:01:01:01
• HLA-A*03:01:01:01
Novel Genotype:
• HLA-A*Novel
• HLA-A*03:01:01:01
 A novel polymorphic site in exon 3 of HLA-A locus
was identified.
 The new SNP (442A>G, Ile124Val) distinguishes this
new allele from its closest match, the relatively
common HLA-A*01:01:01:01 allele.
 The mutation results in a missense mutation that
changes the Isoleucine at codon 124 of the α1 chain
of the mature HLA protein to Valine.
Sequencing Analysis:
RESULTS: Sequencing Analysis

6. SIFT Prediction Tool: (Impact on HLA Function)
Uses conservation degree of A.A. residues in
alignments derived from closely related sequences
that are collected through PSI-BLAST.
I124V substitution is in a highly conserved area:
 Conservation score 3.56/4.32
 Intolerance score of 0.03
I-Mutant Prediction Tool: (Impact on HLA Structure)
Uses the free energy change (ΔΔG) between the
novel and wild-type proteins.
• ΔΔG < -0.5 Kcal/mol are destabilizing mutations
• ΔΔG > 0.5 Kcal/mol are stabilizing,
• (-0.5 < ΔΔG < 0.5 Kcal/mol) are neutral mutations
 I124V has a ΔΔG value of -1.15 Kcal/mol
• Highest Conservation degree = 4.32
(log2(20))  (1 A.A observed)
• Lowest conservation degree = Zero  (20
A.A observed)
• Threshold for intolerance: Probability < 0.05
Figure 5: HLA-A Protein illustrating the
position of the mutated A.A #124 (Isoleucine).
RESULTS: Mutation Impact Analysis

7. CONCLUSION
Novel allele GenBank and WHO Submission:
 The allele was officially named “HLA-A*01:195”
by the WHO Nomenclature Committee in
August 2015 .
 It was accepted by GenBank and successfully
included into IMGT/HLA Database (Accession
Number KT220195).
 I124V mutation is predicted to be intolerant and
possibly deleterious to the HLA-A protein
function and destabilizing to its structure.
ACKNOWLEDGEMENTS:
 The Khalifa University Internal Research Fund Level 1
(KUIRF1)
 Mr. Biduth Radharaman (Technical assistance)
 Mr. Ismahen Ammar (Technical assistance)

8. THANK YOU
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