Targeted next generation sequencing approach identifies nineteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome, Molecular and Cellular Endocrinology (2016), doi: 10.1016/ j.mce.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
AbstractThe genetic basis is unknown for ~60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 19 new candidate genes including:
Urbanization, agriculture, and other land transformations can affect water quality, decrease species biodiversity, and increase metal and nutrient concentrations in aquatic systems. Metal pollution, in particular, is a reported consequence of elevated anthropogenic inputs, especially from urbanized areas. The objectives of this study were to quantify metal (Cu, Al, Cd, Ni, and Pb) concentrations in the waters and biota of four streams in South Georgia, USA, and relate metal concentrations to land use and abiotic and biotic stream processes. Additionally, macrophytes, invertebrates, and fish were identified to assess biodiversity at each site. Metal concentrations in the three trophic levels differed among sites and species, correlating to differences in land use surrounding the rivers. The highest metal concentrations (except Al) were found in the streams most impacted by urbanization and development. Al concentrations were highest in streams surrounded by land dominated by forested areas. Metal content in macrophytes reflected metal concentrations in the water and was at least three orders of magnitude higher than any other trophic level. Despite metal concentration differences, all four streams contained similar water quality and were healthy based on macroinvertebrate community structure. This study provides insight into the impact of urbanization and the fate and effects of metals in river ecosystems with varying degrees of anthropogenic impact.
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