 | Figure 1
Nature Genetics
25, 357 - 361 (2000)
doi:10.1038/77153
Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cystsJuha Paloneva, Marjo Kestilä, Jun Wu, Antti Salminen, Tom Böhling, Vesa Ruotsalainen, Panu Hakola, Alexander B.H. Bakker, Joseph H. Phillips, Petra Pekkarinen, Lewis L. Lanier, Tuomo Timonen
& Leena Peltonen | | | | Figure 1. TYROBP and DAP10, located in opposite transcriptional orientation on chromosome 19q13.1, and identified PLOSL mutations in TYROBP.
a, We performed the PCR across the PLOSLFin deletion from genomic DNA. Primer pair delT/delC revealed a 5.3-kb deletion in all Finnish PLOSL alleles and Alu sequences flanking the deletion. The PLOSLJpn mutation was found in the sequence analysis of the PCR product of exon 3 of TYROBP. The mutation disrupts the reading frame, resulting in a premature stop codon yielding in a 52-aa polypeptide. The functionally critical aspartic acid (D, underlined) at position 50 is changed to threonine (T). The critical markers are indicated. b, The PLOSLFin deletion includes exons 1−4 of TYROBP. The deletion breakpoints are flanked by Alu repetitive elements sharing an identical 23-bp sequence (underlined). Because the deletion breakpoints occur in an identical nucleotide sequence, the precise deletion breakpoints cannot be defined. The PLOSLFin deletion probably arose from homologous recombination between two direct Alu repeats (5.3 kb apart) and resulted in the generation of a fusion Alu element in the disease allele.
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