title: HLA class I variation in Iranian Lur and Kurd populations: high haplotype and allotype diversity with an abundance of KIR ligands.
abstract: HLA-A, -B and -C alleles of 285 individuals, representing three Iranian Lur populations and one Iranian Kurd population were sequenced completely, yielding human leukocyte antigen (HLA) class I genotypes at high resolution and filling four fields of the official HLA nomenclature. Each population has 87-99 alleles, evenly distributed between the three HLA class I genes, 145 alleles being identified in total. These alleles were already known, named and deposited in the HLA database. The alleles form 316 different HLA A-B-C haplotypes, with each population having between 80 and 112 haplotypes. The four Iranian populations form a related group that is distinguished from other populations, including other Iranians. All four KIR ligands - the A3/11, Bw4, C1 and C2 epitopes - are well represented, particularly Bw4, which is carried by three high-frequency allotypes: HLA-A*24:02, HLA-A*32:01 and HLA-B*51:01. In the Lur and Kurd populations, between 82% and 94% of individuals have the Bw4 epitope, the ligand for KIR3DL1. HLA-B*51:01 is likely of Neandertal origin and associated with Behcet's disease, also known as the Silk Road disease. The Lordegan Lur have the highest frequency of HLA-B*51:01 in the world. This allele is present on 46 Lur and Kurd haplotypes. Present at lower frequency is HLA-B*51:08, which is also associated with Behcet's disease. In the four Iranian populations, 31 haplotypes encode both Bw4(+) HLA-A and Bw4(+) HLA-B, a dual combination of Bw4 epitopes that is relatively rare in other populations, worldwide. This study both demonstrates and emphasizes the value of studying HLA class I polymorphism at highest resolution in anthropologically well-defined populations.
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.|Endocrinology and Metabolism Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: E
authors: E
authors: Ashouri
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors: P J
authors: PJ
authors: Norman
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors: L A
authors: LA
authors: Guethlein
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors: A S
authors: AS
authors: Han
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors: N
authors: N
authors: Nemat-Gorgani
authors: Illumina Inc, San Diego, CA, USA.
authors: S J
authors: SJ
authors: Norberg
authors: Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: A
authors: A
authors: Ghaderi
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors: P
authors: P
authors: Parham
mesh_terms: D000483:Alleles; D030541:Databases, Genetic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005006:Ethnicity; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D015234:HLA-A Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007492:Iran; D008024:Ligands; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000145:classification / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA; D009626:Terminology as Topic
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR
keywords: Bw4 epitope; HLA class I polymorphism; HLA-B*51:01; Lur and Kurd populations; high-throughput sequencing