RESUMEN
Chromosome 7q21-22 and, in particular, the region surrounding D7S554 emerged from the recent American genome screen in multiple sclerosis (MS) as the most promising region genome-wide for harboring a disease susceptibility gene. We tested association between D7S554 and MS in 217 Sardinian trio MS families by the transmission disequilibrium test (TDT), and in a Northern Irish case-control study comprising 542 individuals. In both populations, we found evidence for significant allelic association (P(c)=0.04 and P(c)=0.0002, respectively). In a second stage, we analysed five microsatellite markers in a 4 megabase interval on chromosome 7q21-22 in the same set of Sardinian families. Parental transmission of a single allele of one of these markers, i.e. D7S3126, was significantly distorted (P(c)=0.008). D7S554 and D7S3126 are located at distances of, respectively, 40 and 81 kb 5' from the startcodon of the protachykinin-1 gene (TAC1), and occur in strong linkage disequilibrium (P<10(-7)). Our study indicates that the previous finding of linkage with D7S554 refers possibly to the presence of an MS susceptibility effect in vicinity to TAC1. In addition, a second independent association was uncovered between a microsatellite polymorphism in the plasminogen activator inhibitor-1 gene, i.e. D7S477, and MS. Overall, the analysis presented here may contribute to the increasingly refined genomic map of MS and underscores the requirement for a further high-resolution screening of chromosome 7q21-22.
Asunto(s)
Cromosomas Humanos Par 7 , Esclerosis Múltiple/genética , Precursores de Proteínas/genética , Taquicininas/genética , Timosina/análogos & derivados , Adulto , Estudios de Casos y Controles , Salud de la Familia , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Humanos , Irlanda , Italia , Desequilibrio de Ligamiento , Masculino , Repeticiones de Microsatélite , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo Genético , Sustancia P/genética , Timosina/genética , Ubiquitinas/genéticaRESUMEN
Sir Hans Sloane was born in Killyleagh, Co Down, the seventh and last son of Alexander Sloane. His father, who was of Scottish ancestry, had a long association with James Hamilton, Earl of Clanbrassil who had acquired the castle in Killyleagh and extensive estates in east Down. The Hamilton family took an interest in the education of the Sloane children, and much of the early tuition of Hans was conducted within the library of Killyleagh Castle. In 1679 he moved to London to study medicine and botany. In 1683, he continued his studies in Paris and Montpellier, and graduated from the University of Orange. On his return to London, he became a protégé of Thomas Sydenham. In 1687 he was appointed physician to the Duke of Albemarle and surgeon to the West Indies fleet. While in Jamaica he added countless specimens to his collections, continuing a lifetime passion. He also invented milk chocolate there. Following the untimely death of the duke, he returned to London and built up a fashionable medical practice. He married Elizabeth Langley, heiress of a wealthy city alderman, and widow of a sugar planter in Jamaica. They set up house in Great Russell Street. The family home accommodated his burgeoning collections of books, specimens and curiosities. In 1685 he was elected a Fellow of the Royal Society, later becoming the honorary secretary and president. Following his death, his collections were bought for the nation and formed the foundation of the British Museum.