RESUMEN
Full-length KIR2DL1 allele sequence extensions characterised by single molecule real-time (SMRT) DNA sequencing.
Asunto(s)
Genotipo , Intrones/genética , Receptores KIR2DL1/genética , Alelos , Estudios de Cohortes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Polimorfismo de Nucleótido Simple , Reino Unido , Organización Mundial de la SaludRESUMEN
The novel KIR2DL1*037 allele discovered and characterised by single molecule real-time (SMRT) DNA sequencing.
Asunto(s)
Genotipo , Células Asesinas Naturales/fisiología , Receptores KIR2DL1/genética , Población Blanca , Alelos , Línea Celular , Consanguinidad , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Homocigoto , Humanos , Polimorfismo Genético , Alineación de Secuencia , Organización Mundial de la SaludRESUMEN
The hyperpolymorphic HLA genes play important roles in disease and transplantation and act as genetic markers of migration and evolution. A panel of 107 B-lymphoblastoid cell lines (B-LCLs) was established in 1987 at the 10th International Histocompatibility Workshop as a resource for the immunogenetics community. These B-LCLs are well characterised and represent diverse ethnicities and HLA haplotypes. Here we have applied Pacific Biosciences' Single Molecule Real-Time (SMRT) DNA sequencing to HLA type 126 B-LCL, including the 107 International HLA and Immunogenetics Workshop (IHIW) cells, to ultra-high resolution. Amplicon sequencing of full-length HLA class I genes (HLA-A, -B and -C) and partial length HLA class II genes (HLA-DRB1, -DQB1 and -DPB1) was performed. We typed a total of 931 HLA alleles, 895 (96%) of which were consistent with the typing in the IPD-IMGT/HLA Database (Release 3.27.0, January 20, 2017), with 595 (64%) typed at a higher resolution. Discrepant types, including novel alleles (n = 10) and changes in zygosity (n = 13), as well as previously unreported types (n = 34) were observed. In addition, patterns of linkage disequilibrium were distinguished by four-field resolution typing of HLA-B and HLA-C. By improving and standardising the HLA typing of these B-LCLs, we have ensured their continued usefulness as a resource for the immunogenetics community in the age of next generation DNA sequencing.
Asunto(s)
Sistemas de Computación , Antígenos HLA/genética , Inmunogenética , Internacionalidad , Análisis de Secuencia de ADN , Imagen Individual de Molécula , Alelos , Línea Celular , Humanos , Desequilibrio de Ligamiento/genéticaRESUMEN
Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.
Asunto(s)
Citomegalovirus/inmunología , Antígenos HLA/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Donante no Emparentado/provisión & distribución , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Histocompatibilidad , Humanos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Factores de Riesgo , Pruebas Serológicas , Análisis de Supervivencia , Adulto JovenRESUMEN
The genomic sequence of the novel HLA-B*44:220 allele identified in a British Caucasoid male.
Asunto(s)
Alelos , Sustitución de Aminoácidos , Antígeno HLA-B44/genética , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Codón , Exones , Expresión Génica , Antígeno HLA-B44/inmunología , Prueba de Histocompatibilidad , Humanos , Masculino , Datos de Secuencia Molecular , Alineación de Secuencia , Reino Unido , Población BlancaRESUMEN
Genomic sequence of HLA-A*02:95 identified in an Anthony Nolan volunteer donor.