RESUMEN
Nucleotide variants in microRNA regions have been associated with disease; nevertheless, few studies still have addressed the allele-dependent effect of these changes. We studied microRNA genetic variation in human populations and found that while low-frequency variants accumulate indistinctly in microRNA regions, the mature and seed regions tend to be depleted of high-frequency variants, probably as a result of purifying selection. Comparison of pairwise population fixation indexes among regions showed that the seed had higher population fixation indexes than the other regions, suggesting the existence of local adaptation in the seed region. We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B). We found differences in the expression between alleles and in the regulation of several genes involved in cancer, such as TP53, KIT, CDH1, CLH, and TERT, which may result in changes in regulatory networks related to tumorigenesis. Furthermore, luciferase-based assays showed that MIR499A could be regulating the cadherin CDH1 and the cell adhesion molecule CLH1 in an allele-dependent fashion. A better understanding of the effect of microRNA variants associated with disease could be key in our way to a more personalized medicine.
Asunto(s)
MicroARNs/genética , Neoplasias/genética , Regiones no Traducidas 3' , Antígenos CD , Cadherinas/genética , Frecuencia de los Genes , Redes Reguladoras de Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Células HeLa , Humanos , Medicina de PrecisiónRESUMEN
Allele variants HLA-C*01:02:01:74Q and -C*15:02:01:63 differ from -C*01:02:01:01 and -15:02:01:01 by a single nucleotide, respectively.
Asunto(s)
Alelos , Antígenos HLA-C , Humanos , Secuencia de Bases , Prueba de Histocompatibilidad , Antígenos HLA-C/genética , India , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
The novel HLA-DQA1*01:01:01:10 allele differs from HLA-DQA1*01:01:01:07 by a single nucleotide change at gDNA 702 G T.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Análisis de Secuencia de ADN , Cadenas alfa de HLA-DQ/genética , IndiaRESUMEN
Novel HLA-C*06:02:01:94 and -C*15:02:01:58 alleles were detected during the routine HLA typing process.
RESUMEN
The novel allele HLA-C*07:02:01:184 as compared with HLA-C*07:02:01:03 displays polymorphism at position; gDNA 2896 (G > C).
Asunto(s)
Antígenos HLA-C , Humanos , Alelos , Secuencia de Bases , Genes MHC Clase I , Secuenciación de Nucleótidos de Alto Rendimiento , Antígenos HLA-C/genéticaRESUMEN
The novel allele, HLA-B*40:02:01:39 differs from the HLA-B*40:02:01:01 allele by a single nucleotide change at gDNA position 700.
Asunto(s)
Antígenos HLA-B , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Antígenos HLA-B/genética , Genes MHC Clase I , IndiaRESUMEN
The novel allele HLA-A*24:02:01:136 as compared with HLA-A*24:02:01:01 displays a single nucleotide polymorphism at position; gDNA 2827 (C > A).
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Islamismo , Humanos , Secuencia de Bases , Alelos , Antígenos HLA-A/genéticaRESUMEN
The novel allele HLA-C*06:02:38:02 differs from HLA-C*06:02:38:01 by a nucleotide change at position; gDNA 168 T â A.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , India , NucleótidosRESUMEN
The novel allele HLA-A*02:11:01:06 as compared with HLA-A*02:11:01:01 displays polymorphism at position; gDNA 1562 (C>A).
Asunto(s)
Antígenos HLA-A , Humanos , Alelos , Antígenos HLA-A/genéticaRESUMEN
The novel allele HLA-C*03:599 as compared with HLA-C*03:04:01:02 displays polymorphism at position; gDNA 1618 (G>T).
Asunto(s)
Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , AlelosRESUMEN
The novel allele HLA-A*11:01:01:86 differs from HLA-A*11:01:01:86 by one nucleotide change at position; gDNA-32 (A- > C).
Asunto(s)
Antígenos HLA-A , Nucleótidos , Humanos , Alelos , India , Antígenos HLA-A/genética , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The novel allele HLA-C*04:01:01:129 as compared to HLA-C*04:01:01:01 displays polymorphism at two positions; gDNA 2905 (C â T) and 2910 (T â A).
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Alelos , Antígenos HLA-C/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , India , Polimorfismo GenéticoRESUMEN
The HLA-B*51:01:01:108 and HLA-B*40:387 alleles were detected during routine HLA typing.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Antígenos HLA-B/genética , Prueba de Histocompatibilidad , Pueblo Asiatico , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The novel allele HLA-DQB1*04:02:01:18 differs from HLA-DQB1*04:02:01:04 by a nucleotide change at position; gDNA 2789 A â G.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Secuencia de Bases , Cadenas beta de HLA-DQ/genética , IndiaRESUMEN
The novel alleles HLA-A*68:175:02 and -A*68:287 each differ from -A*68:01:02:02 by a single nucleotide.
Asunto(s)
Antígenos HLA-A , Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Antígenos HLA-A/genética , Humanos , NucleótidosRESUMEN
A novel HLA-B*07:461 and an extended HLA-C*15:193 allele were detected during routine HLA typing process.
Asunto(s)
Antígeno HLA-B7 , Antígenos HLA-C , Alelos , Secuencia de Bases , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Secuenciación de Nucleótidos de Alto Rendimiento , HumanosRESUMEN
The novel allele HLA-DPB1*02:01:61 as compared with HLA-DPB1*02:01:02 displays polymorphism by a single nucleotide at gDNA 9011 C->T.