RESUMEN
HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas HLA-DRB4 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Cadenas HLA-DRB4/genética , Codón , Alineación de SecuenciaRESUMEN
Two novel non-classical HLA class I alleles have been characterized, HLA-F*01:16 and -F*01:17.
Asunto(s)
Genes MHC Clase I , Donantes de Tejidos , Humanos , AlelosRESUMEN
Sequence confirmations of 175 HLA class I and II alleles in the IPD-IMGT/HLA Database.
Asunto(s)
Alelos , Bases de Datos Genéticas , Antígenos de Histocompatibilidad Clase II , Antígenos de Histocompatibilidad Clase I , Humanos , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Análisis de Secuencia de ADN , Prueba de HistocompatibilidadRESUMEN
Two novel alleles, HLA-G*01:04:09 and HLA-DPB1*04:01:01:136, were identified in a single healthy individual.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-G , Humanos , Alelos , Cadenas beta de HLA-DP/genéticaRESUMEN
A total of 43 novel HLA alleles detected in haematopoietic cell donors using single molecule real-time DNA sequencing.
Asunto(s)
Alelos , Antígenos HLA , Prueba de Histocompatibilidad , Donantes de Tejidos , Humanos , Antígenos HLA/genética , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Trasplante de Células Madre Hematopoyéticas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Células Madre Hematopoyéticas/metabolismoRESUMEN
Genetic variation in the MICA and MICB genes located within the major histocompatibility complex region has been reported to be associated with transplantation outcome and susceptibility to autoimmune diseases and infections. Only limited data of polymorphism in these genes in different populations are available. We here report allelic variation at 2-field resolution and the haplotypes of the MICA and MICB genes in Finland (n = 1032 individuals), a north European population with historical bottleneck and founder effects. Altogether 24 MICA and 18 MICB alleles were found, forming 70 estimated MICA-MICB haplotypes. As compared to other populations frequency differences were found, for example, MICA*010:01 was found to be at an allele frequency of 0.133 in Finland which is higher than in other European populations (0.021-0.077), but close to Asian populations (0.151-0.220). Three novel alleles with amino acid change are described. The results demonstrate a relatively high level of polymorphism and population differences in MICA and MICB allele distribution.
Asunto(s)
Antígenos de Histocompatibilidad Clase I , Polimorfismo Genético , Humanos , Alelos , Antígenos de Histocompatibilidad Clase I/genética , Finlandia , Frecuencia de los Genes , HaplotiposRESUMEN
Until recently the number of alleles of the nonclassical HLA class I gene HLA-E documented in the IPD-IMGT/HLA Database was small and as a result, the gene was often not considered to be notably polymorphic. Here, we describe our work in identifying and submitting 86 novel HLA-E alleles after full-gene single-molecule real-time (SMRT) DNA sequencing of 6227 DNA samples. These samples were comprised of 2468 patients undergoing hematopoietic cell transplantation and 3759 unrelated potential donors. A total of 111 unique HLA-E alleles were detected in this cohort. The majority of novel alleles (79.1%) contained polymorphisms in intronic regions, highlighting the significant undiscovered variation present in the noncoding regions of the HLA-E gene.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Alelos , Antígenos HLA-ERESUMEN
HLA-E*01:03:02:25 sequenced from blood and buccal samples of an ALL patient.
Asunto(s)
Antígenos de Histocompatibilidad Clase I , Leucemia-Linfoma Linfoblástico de Células Precursoras , Alelos , Antígenos de Histocompatibilidad Clase I/genética , Prueba de Histocompatibilidad , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Antígenos HLA-ERESUMEN
Pacific Biosciences SMRT sequencing used to identify the novel allele, HLA-A*02:01:02:206.
Asunto(s)
Antígenos HLA-A , Población Blanca , Alelos , Antígenos HLA-A/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Análisis de Secuencia de ADNRESUMEN
As the primary genetic determinant of immune recognition of self and non-self, the hyperpolymorphic HLA genes play key roles in disease association and transplantation. The large, variably sized HLA class II genes have historically been less well characterized than the shorter HLA class I genes. Here, we have used Pacific Biosciences Single Molecule Real-Time (SMRT®) DNA sequencing to perform four-field resolution HLA typing of HLA-DRB1/3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 from a panel of 181 B-lymphoblastoid cell lines from the International HLA and Immunogenetics Workshops. By interrogating all exons, introns, and the untranslated regions of these important reference cells, we have improved their HLA typing resolution on the IPD-IMGT/HLA database. We observed widespread non-coding polymorphism, with over twice as many unique genomic sequences identified compared with coding sequences (CDS). We submitted 263 unique sequences to the IPD-IMGT/HLA Database, often from multiple cell lines, including 114 confirmations of existing alleles, of which 30 were also extensions to full-length genomic sequences where only CDS was available previously. A total of 149 novel alleles were identified, largely differing from their closest reference allele sequences by a single nucleotide polymorphism (SNP). However, some highly divergent alleles were deemed to be recombinants, only detectable by full-length sequencing with long, phased reads. The fourth-field variation we observed allowed fine mapping of linkage disequilibrium patterns and haplotypes to particular ancestries. This study has highlighted the under-appreciated non-coding diversity in HLA class II genes, with potential implications for population genetic and clinical studies.
Asunto(s)
Genes MHC Clase II , Inmunogenética , Alelos , Línea Celular , Frecuencia de los Genes , Haplotipos , HumanosRESUMEN
A novel variant of HLA-C*03:04:01:47 was identified using Pacific Biosciences SMRT sequencing platform.
Asunto(s)
Antígenos HLA-C , Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Genes MHC Clase I , Antígenos HLA-C/genética , Humanos , Análisis de Secuencia de ADNRESUMEN
We have developed a genotyping assay that produces fully phased, unambiguous HLA-E genotyping using Pacific Biosciences' single molecule real-time DNA sequencing. In total 212 cell lines were genotyped, including the panel of 107 established at the 10th International Histocompatibility Workshop. Our results matched the previously known HLA-E genotype in 94 (44.3%) cell lines, in all cases either improving or equalling previous genotyping resolution. Three (1.4%) cells had discrepant HLA-E genotyping data and 115 (54.2%) had no previous HLA-E data. The HLA-E genotypes for four (1.9%) cell lines resulted in a change of zygosity by identifying two distinct haplotypes. We discovered eight novel HLA-E alleles, extended the known reference sequence of seven and confirmed the existence of a further 10.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Antígenos de Histocompatibilidad Clase II , Alelos , Línea Celular , Genotipo , Antígenos HLA , Antígenos de Histocompatibilidad Clase II/genética , Prueba de Histocompatibilidad , Análisis de Secuencia de ADNRESUMEN
Pacific Biosciences' SMRT sequencing method was used to extend the sequence of HLA-A*02:13.