Suchergebnisse

BACKGROUND: In a Danish family, multiple individuals in five generations present with early‐onset paroxysmal cranial dyskinesia, musculoskeletal abnormalities, and kidney dysfunction. OBJECTIVE: To demonstrate linkage and to identify the underlying genetic cause of disease. METHODS: Genome‐wide single‐nucleotide polymorphisms analysis, Sequence‐Tagged‐Site marker analyses, exome sequencing, and Sanger sequencing were performed. RESULTS: Linkage analyses identified a candidate locus on chromosome 9. Exome sequencing revealed a novel variant in LMX1B present in all affected individuals, logarithm of the odds (LOD) score of z = 6.54, predicted to be damaging. Nail‐patella syndrome (NPS) is caused by pathogenic variants in LMX1B encoding a transcription factor essential to cytoskeletal and kidney growth and dopaminergic and serotonergic network development. NPS is characterized by abnormal musculoskeletal features and kidney dysfunction. Movement disorders have not previously been associated with NPS. CONCLUSIONS: Paroxysmal dyskinesia is a heretofore unrecognized feature of the NPS spectrum. The pathogenic mechanism might relate to aberrant dopaminergic circuits. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

We report here the genome sequence of an ancient human. Obtained from ∼4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit. ; Centre for Geogenetics, the Copenhagen branch of the Sino-Danish Genomic Centre and Wilhelm Johannsen Centre for Functional Genome Research were supported by Danish National Research Foundation, the Lundbeck Foundation, and the Danish Agency for Science, Technology and Innovation. Center for Biological Sequence Analysis was supported by Villum Kann Rasmussen Fonden; Center for Protein Reseaerch by the Novo Nordisk Foundation. E.W. thanks F. Paulsen for financial support to initiate the project. E.M. thanks Estonian Science Foundation for grant 7858, and R.V. EC DGR for FP7 Ecogene grant 205419 and EU RDF through Centre of Excellence in Genomics grant. J.W. thanks the Shenzhen Municipal Government, the Yantian District local government of Shenzhen, the National Natural Science Foundation of China (30725008), Ole Romer grant from the Danish Natural Science Research Council, the Solexa project (272-07-0196), and Danish Strategic Research Council (2106-07-0021). M.Bu. acknowledges the support of the ...