RESUMEN
Multiciliated epithelial cells protect the upper and lower airways from chronic bacterial infections by moving mucus and debris outward. Congenital disorders of ciliary beating, referred to as primary ciliary dyskinesia (PCD), are characterized by deficient mucociliary clearance and severe, recurrent respiratory infections. Numerous genetic defects, most of which can be detected by transmission electron microscopy (TEM), are so far known to cause different abnormalities of the ciliary axoneme. However, some defects are not regularly discernable by TEM because the ciliary architecture of the axoneme remains preserved. This applies in particular to isolated defects of the nexin links, also known as the nexin-dynein regulatory complex (N-DRC), connecting the peripheral outer microtubular doublets. Immunofluorescence analyses of respiratory cells from PCD-affected individuals detected a N-DRC defect. Genome-wide exome sequence analyses identified recessive loss-of-function mutations in GAS8 encoding DRC4 in three independent PCD-affected families.
Asunto(s)
Proteínas del Citoesqueleto/genética , Dineínas/antagonistas & inhibidores , Síndrome de Kartagener/etiología , Complejos Multiproteicos/antagonistas & inhibidores , Mutación/genética , Proteínas de Neoplasias/genética , Nexinas de Proteasas/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales , Adulto , Animales , Western Blotting , Niño , Cilios/fisiología , Dineínas/genética , Exoma/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/fisiología , Síndrome de Kartagener/patología , Masculino , Proteínas de la Membrana , Ratones , Ratones Noqueados , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Complejos Multiproteicos/genética , Mucosa Nasal/citología , Mucosa Nasal/metabolismo , Óxido Nítrico/análisis , Linaje , Fenotipo , Pronóstico , Nexinas de Proteasas/genética , Sistema Respiratorio , Adulto JovenRESUMEN
OBJECTIVE: To investigate the genetic polymorphisms of rs2229338 and rs12218 loci of serum amyloid protein A1 (SAA1) gene in healthy Chinese Han and Uighur populations of Xinjiang. METHODS: The genotypes of the SAA1 gene were detected in 316 Uighur and 362 Han healthy individuals by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The genotype distributions of both populations were in the Hardy-Weinberg equilibrium (both P>0.05). The frequencies of AA, AG and GG genotypes of the rs2229338 locus were 76.6%, 23.4%, and 0 in the Uighurs, and 91.7%, 7.7% and 0.6% in the Hans. There was significant difference in distribution of genotypes between the two populations (P<0.01). The frequencies of CC, CT and TT genotypes of the rs12218 locus were 10.1%, 47.5%, and 42.4% in Uighurs, and 3.3%, 34.3% and 62.4% in Hans. There was also significant difference in distribution of genotypes between the two populations (P<0.01). The A-C and G-T haplotypes were more frequent in the Uighur but the A-T haplotype was more common in the Han population, respectively (both P<0.01). CONCLUSION: The mutational frequencies of the tagging SNPs in rs2229338 and rs12218 loci of theSAA1 gene in the Uighurs may be higher than those in Hans.
