RESUMEN
TATA-box binding protein associated factor 1 (TAF1) protein is the largest and the essential component of the TFIID complex in the pathway of RNA polymerase II-mediated gene transcription, and it regulates transcription of a large number of genes related to cell division. The neuron-specific isoform of the TAF1 gene (N-TAF1), which we reported previously, may have an essential role in neurons through transcriptional regulation of many neuron-specific genes. In the present study, we cloned the full-length cDNA that encodes the mouse homologue of N-TAF1 (N-Taf1) protein. By carrying out of real time RT-PCR, we investigated the expression analysis of the N-Taf1 mRNA in mouse tissues and cell lines. As well as the human N-TAF1, the N-Taf1 showed limited expression in the brain and neuroblastoma, whereas Taf1 expressed elsewhere. Furthermore, in mouse embryo head or mouse brain, mRNA expression of TAF1 changes dramatically during development but N-Taf1 showed sustained expression. Our result suggests that the N-Taf1 gene has an important role in non-dividing neuronal cell rather than in cell division and proliferation during neurogenesis.
Asunto(s)
Envejecimiento/genética , Regulación del Desarrollo de la Expresión Génica , Neurogénesis/genética , Neuronas/fisiología , Isoformas de Proteínas/genética , Factores Asociados con la Proteína de Unión a TATA/genética , Factor de Transcripción TFIID/genética , Animales , Secuencia de Bases , Encéfalo/embriología , Encéfalo/metabolismo , División Celular/genética , Línea Celular Tumoral , Proliferación Celular , Clonación Molecular , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Exones/genética , Cabeza/embriología , Histona Acetiltransferasas , Humanos , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Neuronas/citología , Sistemas de Lectura Abierta/genética , ARN Mensajero/biosíntesisRESUMEN
We performed a genome-wide association study with 23,465 microsatellite markers to identify genes related to adult height. Selective genotyping was applied to extremely tall and extremely short individuals from the Khalkh-Mongolian population. Two loci, 8q21.13 and 15q22.33, which showed the strongest association with microsatellites were subjected to further analyses of SNPs in 782 tall and 773 short individuals. The most significant association was observed with SNP rs2220456 at 8q21.13 (P = 0.000016). In the LD block at 15q22.32, SNP rs8038652 located in intron 1 of IQCH was strongly associated (P = 0.0003), especially the AA genotype of the SNP under a recessive model was strongly associated with adult height (P = 0.000046).
Asunto(s)
Estatura/genética , Mapeo Cromosómico , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 8 , Ligamiento Genético , Sitios de Carácter Cuantitativo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Frecuencia de los Genes , Genética de Población , Genoma Humano , Genotipo , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Mongolia , Polimorfismo de Nucleótido SimpleRESUMEN
Hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) is an adult-onset peripheral neurodegenerative disorder which has been reported only in the Okinawa Islands, Japan. The disease locus of "Okinawa-type" HMSN-P has been previously mapped to 3q13.1, with all affected individuals sharing an identical haplotype around the locus, suggesting that the undiscovered causative mutation in HMSN-P originated from a single founder. We have newly found two large families from the western part of Japan within which multiple members developed symptoms similar to those exhibited by HMSN-P patients from Okinawa, with no record of affinal connection between the islands. Using these pedigrees with "Kansai-type" HMSN-P, we carried out a linkage study utilizing eight microsatellite markers and identified a candidate region on 3q13.1 cosegregating with the disease (maximum two-point LOD score of 8.44 at theta=0.0) overlapping with the Okinawa-type HMSN-P locus. However, the disease haplotype shared among all affected members in these families was different from that in the Okinawa kindred, suggesting allelic heterogeneity. Such allelic variation should aid in the identification of the disease-causative gene. Moreover, the allelic heterogeneity of HMSN-P in the Japanese population suggests that HMSN-P may be more common across other ethnic groups, but classified into other disease categories.
