RESUMO
South Indians are a heterogeneous population who speak different languages and differ in their life style and physical appearance. Major population movements, social structure and caste endogamy have influenced the genetic structure of Indian populations. The human leukocyte antigen (HLA) system of populations is highly informative because of the high level of polymorphisms. Knowledge of allele and haplotype frequencies of the HLA system is important in the search for unrelated bone marrow donors. We investigated the distribution of HLA A, B, C, DRB1 and DQB1 loci in five linguistic groups from South India. HLA-A*01:01:01~B*57:01:01:01~C*06:02:01~DRB1*07:01:01~DQB1*03:03:02 was the common haplotype with highest frequency in all the five populations studied. A few relevant haplotypes were identified as most common haplotypes in each linguistic group. Comparison of HLA-A, -B and -DRB1 allele distribution in these five linguistic groups with the other Asian population showed that the South Indian populations were closely related to Sri Lankan populations. A large South Indian donor registry might serve as good source of donors for patients from Sri Lanka and vice versa.
Assuntos
Genes MHC da Classe II , Linguística , Alelos , Frequência do Gene , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , ÍndiaRESUMO
BACKGROUND: Schizophrenia, a chronic severe psychiatric illness of unknown aetiology, has been shown to be associated with HLA alleles but at varied degree in different population. The present study has focussed on analysing the frequency of HLA class I and class II alleles in persons with schizophrenia from South India. METHODS: Ninety seven individuals with schizophrenia and 103 age- and gender-matched controls were typed for HLA- A, B, C, DRB1 and DQB1 loci by next-generation sequencing in Illumina MiniSeq using MIA FORA NGS FLEX HLA typing kit. RESULTS: The results showed that HLA-A*01:01:01, B*37:01:01 and C*01:02:01 were positively associated with schizophrenia while HLA-B*35:03:01 and DRB1*04:03:01 were negatively associated. Gender-specific associations revealed that DRB1*10:01:01 and DQB1*05:01:01 were positively associated while DQB1*03:02:01 was negatively associated with female subjects with schizophrenia. A*24:02:01~B*37:01:01~C*06:02:01~DRB1*10:01:01~DQB1*05:01:01 is the predominant haplotype in schizophrenia population when compared to healthy controls. Amino acid association in susceptible and protective alleles has shown that the presence of peptide in the peptide-binding groves of mature HLA-A protein (K, M, V, R and V at 44th, 67th, 150th, 156th and 158th position), HLA-B protein (D and S at 77th and 99th position) and HLA-C protein (M at 99th position) confer susceptibility to the disease, only in the absence of E (Glutamic acid) at 74th position in mature HLA-DRB1 protein. Interaction of amino acids in protective alleles namely B*35:01:01 and DRB1*04:03:01 has revealed that aspartic acid at 114th (D) position in mature HLA-B protein and glutamic acid (E) at 74th position of mature HLA-DRB1 protein have a combined effect in protecting against the disease. CONCLUSION: The study has revealed the HLA association with schizophrenia in south Indian population. The amino acid interaction with the disease needs to be confirmed in a larger population.
Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Esquizofrenia/genética , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Teste de Histocompatibilidade , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Esquizofrenia/imunologia , Fatores SexuaisAssuntos
Pustulose Exantematosa Aguda Generalizada/genética , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Antígenos HLA-B/sangue , Pustulose Exantematosa Aguda Generalizada/sangue , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/imunologia , Alelos , Carbamazepina/efeitos adversos , Epilepsia/diagnóstico , Predisposição Genética para Doença , Antígenos HLA-B/imunologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fenitoína/efeitos adversosRESUMO
The novel HLA-B allele, HLA-B*35:03:23, differs from B*35:03:01 by a single-nucleotide mismatch in exon 1.
Assuntos
Alelos , Antígenos HLA-B/genética , Sequenciamento de Nucleotídeos em Larga Escala , Sequência de Bases , Éxons/genética , Teste de Histocompatibilidade , HumanosRESUMO
Identification of the novel allele HLA-B*40:379 carrying polymorphisms in an intron, exon and the 3' untranslated region.
Assuntos
Alelos , Antígeno HLA-B40/genética , Sequenciamento de Nucleotídeos em Larga Escala , Regiões 3' não Traduzidas/genética , Sequência de Bases , Éxons/genética , HumanosAssuntos
Antígenos HLA-A/genética , Antígeno HLA-B27/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Alelos , Etnicidade , Expressão Gênica , Frequência do Gene , Genética Populacional , Antígenos HLA-A/imunologia , Antígeno HLA-B27/imunologia , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Humanos , Índia , Idioma , Polimorfismo GenéticoRESUMO
HLA A: B:C:DRB1:DQB1 allele and haplotype frequencies were determined among India, Andhra Pradesh, Telugu speaking population from South India by Next Generation Sequencing. 180 bone marrow registry donors and 6 cord blood units from Jeevan Stem Cell Foundation (part of Be The Cure Registry), Chennai, Tamilnadu state were included in the study.
