Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.

Federal Authority and the Development of Corporate Mining, 1807-1847

While the 1913-1914 copper country miners’ strike undoubtedly plays an important role in the identity of the Keweenaw Peninsula, it is worth noting that the model of mining corporations employing large numbers of laborers was not a foregone conclusion in the history of American mining. Between 1807 and 1847, public mineral lands in Missouri, in the Upper Mississippi Valley, and along the southern shore of Lake Superior were reserved from sale and subject to administration by the nation’s executive branch. By decree of the federal government, miners in these regions were lessees, not landowners. Yet, in the Wisconsin lead region especially, federal authorities reserved for independent “diggers” the right to prospect virtually unencumbered. In doing so, they preserved a comparatively egalitarian system in which the ability to operate was determined as much by luck as by financial resources. A series of revolts against federal authority in the early nineteenth century gradually encouraged officers in Washington to build a system in the copper country in which only wealthy investors could marshal the resources to both obtain permits and actually commence mining operations. This paper will therefore explore the role of the federal government in establishing a leasing system for public mineral lands in the years previous to the California Gold Rush, highlighting the development of corporate mining which ultimately set a stage for the wave of miners’ strikes in the late nineteenth and early twentieth centuries.