RESUMEN
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.
Asunto(s)
Etnicidad , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Polimorfismo Genético , Receptores KIR/genética , Alelos , Bases de Datos Genéticas , Epítopos/química , Epítopos/inmunología , Expresión Génica , Frecuencia de los Genes , Genotipo , Antígenos HLA-A/clasificación , Antígenos HLA-A/inmunología , Antígenos HLA-B/clasificación , Antígenos HLA-B/inmunología , Antígenos HLA-C/clasificación , Antígenos HLA-C/inmunología , Haplotipos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Irán , Ligandos , Receptores KIR/clasificación , Receptores KIR/inmunología , Análisis de Secuencia de ADN , Terminología como AsuntoRESUMEN
Killer-cell immunoglobulin-like receptors (KIR) control the function of natural killer cells. The number and type of KIR genes are substantially variable among individuals. Sequence-specific primer-directed polymerase chain reaction (SSP-PCR) based genotyping is the most commonly used method to assess the KIR gene content. However, it requires a minimum of 16 gene-specific amplifications and often yields false-negative results. Herein, we describe the development of a simple and efficient duplex SSP-PCR assay to identify the presence and absence of 16 KIR genes. This system further distinguishes subsets of KIR2DS4 and KIR3DP1 alleles. The assay was subjected to a blind validation using a panel of 78 reference DNA standards from the UCLA KIR Exchange Program, which showed 100% specificity and accuracy. Compared with the conventional SSP typing methods, the present method is an accurate, simple, cost-effective and labor-saving KIR genotyping method for high volume testing.
Asunto(s)
Reacción en Cadena de la Polimerasa/métodos , Receptores KIR/genética , Análisis de Secuencia de ADN/métodos , Alelos , Genotipo , Humanos , Células Asesinas Naturales/inmunología , Sensibilidad y EspecificidadRESUMEN
Bernard-Soulier syndrome (BSS) is a rare recessively inherited bleeding disorder caused by the deficiency of the platelet glycoprotein (Gp) complex Ib/IX/V that is the von Willebrand factor receptor on platelets. In patients suffering from BSS platelet adhesion is typically impaired, while platelet aggregation is normal; macrothrombocytopenia is a common feature. In this study three different families from Southern Iran were investigated. GpIb/IX/V platelet expression as detected by flow cytometry was less than 2% of normal in six cases and 12% in the remaining one. Platelet count was 35,000 platelets/microliter and iron deficiency anemia was common. All patients suffered from mucocutaneous bleeding at presentation and were born from consanguineous marriages. Genetic analysis demonstrated the presence of the same GpIX Phe55Ser missense mutation in two families and of a single base insertion (GP1BA C3221 ins), a never described mutation causing a frameshift in the GpIbalpha gene, in the third family. Among the family members studied several heterozygotes were identified. None of them, with one exception, had macrothrombocytopenia. In one family a slight reduction of GpIb/IX/V expression was observed.
Asunto(s)
Síndrome de Bernard-Soulier/genética , Mutación , Complejo GPIb-IX de Glicoproteína Plaquetaria/genética , Glicoproteínas de Membrana Plaquetaria/genética , Receptores de Superficie Celular/genética , Plaquetas , Análisis Mutacional de ADN , Salud de la Familia , Mutación del Sistema de Lectura , Humanos , Irán , Mutación Missense , Glicoproteínas de Membrana Plaquetaria/análisis , Receptores de Superficie Celular/análisis , TrombocitopeniaRESUMEN
Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) are two rare inherited disorders of platelet function. In this study, we report the demographic, clinical and biological characteristics of 23 patients with GT and of seven patients with BSS from southern Iran who had been followed for many years but fully characterized only recently, when platelet aggregation tests and flow cytometric studies became available for the first time in the country. We found a high prevalence of both diseases that can be explained by the high rate of consanguineous marriages in south Iran. Patients affected by GT and BSS suffer mainly from mucocutaneous bleedings causing anemia and transfusion requirements.
