Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype

Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD. Objectives: To identify disease-causingmutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD. Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing. Sanger-based sequencing was used for mutation scanning, validation, and segregation analysis. Measurements and Main Results: We performed exome sequencing on an affected sib-pair with normal ultrastructure in more than 85% of cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings; parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325 with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of-function mutations in nine additional probands. Five affected siblings of probands in RSPH1 families harbored the familial mutations. The 16 individuals with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7 nl/min; P , 0.0003). Additionally, individuals with RSPH1 mutations had a lower prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily wet cough than typical for PCD, and better lung function (FEV1), compared with 75 age- and sex-matched PCD cases (73.0 vs. 61.8, FEV1 % predicted; P = 0.043). Cilia from individuals with RSPH1 mutations had normal beat frequency (6.16Hz at 258C), but an abnormal, circular beat pattern. Conclusions: The milder clinical disease and higher nasal nitric oxide in individuals with biallelic mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship in PCD, and suggests that mutations in RSPH1 may be associated with residual ciliary function

La Produccion de Alimentos y la Crisis Energetica

By the year 1975, the world population is expected to reach 4 billion human beings. As the population continues to grow, there will be growing concern about how to prevent or avoid large-scale famine. Concurrently, an energy crisis (caused by fuel shortages and high fuel prices) is expected as the world's population continues  as reserves of the non-renewable resource of fuels are rapidly depleting. The energy crisis is also expected to have a significant impact on production technology,on food production technology in the United States and on the "green revolution"  because both crop production systems depend on large inputs of energySe espera que para el año 1975 la poblacion mundial alcance la cifra de 4 billones de seres humanos. Segun continue creciendo la poblacion crecera la preocupacion sobre como prevenir o evitar una hambruna en gran escala. Concurrentemente se espera una crisis energetica (causada por escasez de combustibles y precios altos de los mismos) al paso que se vayan agotando rapidamente las reservas del recurso no renovable que son los combustibles de origen fosil. Se espera tambien que la crisis energetica tenga un impacto significativo en la tecnologfa de la produccion de alimentos en los Estados Unidos y en la "revolucion verde" porque ambos sistemas de produccion de cosechas dependen de grandes insumos de energia