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Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis(More)
We observed a severe autosomal recessive movement disorder in mice used within our laboratory. We pursued a series of experiments to define the genetic lesion underlying this disorder and to identify a cognate disease in humans with mutation at the same locus. Through linkage and sequence analysis we show here that this disorder is caused by a homozygous(More)
A persistent mystery about the ataxias has been why mutations in genes--many of which are expressed widely in the brain--primarily cause ataxia, and not, for example, epilepsy or dementia. Why should a polyglutamine stretch in the TATA-binding protein (that is important in all cells) particularly disrupt cerebellar coordination? We propose that advances in(More)
BACKGROUND Deletions in ITPR1, coding for the inositol-triphosphate receptor type 1, have been recently identified in spinocerebellar ataxia type 15 (SCA15). OBJECTIVE To determine the frequency and the phenotypical spectrum of SCA15. DESIGN Taqman polymerase chain reaction (258 index cases) or single-nucleotide polymorphism genome-wide genotyping (75(More)
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has(More)
Using paired-end RNA sequencing, we have quantified the deep transcriptional changes that occur during differentiation of murine embryonic stem cells into a highly enriched population of glutamatergic cortical neurons. These data provide a detailed and nuanced account of longitudinal changes in the transcriptome during neurogenesis and neuronal maturation,(More)
Spinocerebellar ataxia type 20 (SCA20) has been linked to chromosome 11q12, but the underlying genetic defect has yet to be identified. We applied single-nucleotide polymorphism genotyping to detect structural alterations in the genomic DNA of patients with SCA20. We found a 260 kb duplication within the previously linked SCA20 region, which was confirmed(More)
Old English Sheepdogs and Gordon Setters suffer from a juvenile onset, autosomal recessive form of canine hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex. The clinical and histological characteristics are analogous to hereditary ataxias in humans. Linkage and genome-wide association studies on a cohort of related Old(More)
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