PMC:1892049 / 7618-9641 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1892049","sourcedb":"PMC","sourceid":"1892049","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1892049","text":"We obtained genomic DNA from three affected family members and one family member with unknown disease status from the kindred originally used to define and map SCA15 (family AUS1, of Australian Anglo-Celtic origin) [2]. We performed two experiments concurrently in three affected members of this family: sequence analysis of the coding exons of ITPR1 and high-density genome-wide SNP genotyping. Sequence analysis failed to show any coding alterations segregating with disease or any alterations that were inconsistent with Mendelian patterns of inheritance within the family. However, visualization of log R ratio and B allele frequency metrics from the genome-wide SNP genotyping experiments clearly showed data consistent with a heterozygous genomic deletion across the first one-third of ITPR1 and across the first half of a neighboring gene, SUMF1 (Figure 2). This deletion was apparent in all three affected family members studied and absent from the family member with unknown affection status (Figure 3). The SNP data showed a deletion of between 188 kb and 210 kb in size; examination of SNPs at the flanking unknown regions of this deletion allowed us to delimit the borders of the deletion to 7.5 kb on the telomeric side of the deletion (between rs12634249 and rs793396) and ~14.4 kb on the centromeric side of the deletion (between rs4073665 and rs17709863). In an attempt to define whether this variation was a benign polymorphism we analyzed genome-wide SNP data at this locus, produced using the same genotyping chip, from 577 individuals of European descent who were either controls or individuals with an unrelated neurological disorder. We failed to find any deletions affecting the coding sequence of either gene, ITPR1 or SUMF1; we did, however, identify a single individual with a possible heterozygous deletion approximately 6 kb in size within intron 40–41 of ITPR1, at least 5 kb away from exon 40. Given the location of this alteration it is unlikely to effect the expression or splicing of 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