Asunto(s)
Duplicación de Gen , Patrón de Herencia , Familia de Multigenes , Globinas alfa/genética , Talasemia beta/genética , Alelos , Estudios de Asociación Genética , Genómica/métodos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Linaje , Talasemia beta/diagnósticoRESUMEN
We describe a novel deletion causing ÎµÎ³Î´ß thalassemia in a Pakistani family. The Pakistani deletion is 506kb in length, and the second largest ÎµÎ³Î´ß thalassemia deletion reported to date. It removes the entire ß globin gene (HBB) cluster, extending from 431kb upstream to 75kb downstream of the ε globin gene (HBE). The breakpoint junction occurred within a 160bp palindrome embedded in LINE/LTR repeats, and contained a short (9bp) region of direct homology which may have contributed to the recombination event. Characterization of the deletion breakpoints has been particularly challenging due to the complexity of DNA deletion, insertion and inversion, involving a multitude of methodologies, mirroring the changing DNA analysis technologies.
Asunto(s)
Globinas beta/genética , Talasemia beta/genética , Globinas delta/genética , Talasemia delta/genética , Globinas épsilon/genética , gamma-Globinas/genética , Adulto , Secuencia de Bases , Puntos de Rotura del Cromosoma , Cromosomas Humanos Par 11 , Femenino , Recombinación Homóloga , Humanos , Lactante , Secuencias Invertidas Repetidas , Elementos de Nucleótido Esparcido Largo , Masculino , Datos de Secuencia Molecular , Familia de Multigenes , Análisis de Secuencia de ADN , Eliminación de SecuenciaRESUMEN
Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.