Two Distinct Deletions in theIDSGene and the GeneW: A Novel Type of Mutation Associated with the Hunter Syndrome

Karsten, Stanislav L.; Lagerstedt, Kristina; Carlberg, Britt-Marie; Kleijer, Wim J.; Zaremba, Jacek; Diggelen, O. P. van; Czartoryska, Barbara; Pettersson, Ulf; Bondeson, Marie-Louise

doi:10.1006/geno.1997.4811

Cited by 25 publications

(16 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Minisatellites have been shown to be highly recombinogenic (26) and involved in genomic rearrangements leading to cancer (27). Short stretches of sequence homology are sufficient for recombination and have been observed in several other chromosomal rearrangements: the sequences at each end of the mouse pink-eyed unstable (p un ) duplication match eight of nine bp from the consensus sequence of DNA gyrase sites (25); and the sequence TACTCTA occurs at both deletion junctions in Hunter syndrome (28). In contrast, there is no extended region of homology between the two ends of the Wld s repeat unit such as that which occurs in the CMT1A duplication (19,29).…”

Section: Discussionmentioning

confidence: 99%

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

Coleman

Conforti

Buckmaster

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

174

127

View full text Add to dashboard Cite

Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL͞Wld s ) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL͞Wld s among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences (''illegitimate'' or ''nonhomologous'' recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wld s mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.

show abstract

Section: Discussionmentioning

confidence: 99%

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

Coleman

Conforti

Buckmaster

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

174

127

View full text Add to dashboard Cite

show abstract

“…Conversely, it is possible that these gene-duplication events reflect the relative instabil- ity of this chromosome region and that they are relevant to the deletions and translocations that are frequently mapped to 1p36.3. Karsten and colleagues have suggested that a double deletion involving the IDS and W genes in a Hunter syndrome patient may be the result of homology-associated nonhomologous recombinations caused by the presence of similarly large duplicated regions on human chromosome X band q28 (Karsten et al 1997). Either way, it will be of interest to determine whether additional tandemly duplicated genes are localized to this region of chromosome 1 and if such duplications are a common feature of other human chromosomes.…”

Section: Discussionmentioning

confidence: 99%

Duplication of a Genomic Region Containing the Cdc2L1-2 and MMP21-22 Genes on Human Chromosome 1p36.3 and their Linkage to D1Z2

Gururajan¹,

Lahti²,

Grenet³

et al. 1998

Genome Res.

View full text Add to dashboard Cite

Cdc2L1 and Cdc2L2 span ∼140 kb on human chromosome 1p36.3. The products of the Cdc2L genes encode almost identical protein kinases, the PITSLRE kinases, which have functions that may be relevant to the regulation of transcription/splicing and apoptotic signaling. These genes are deleted/translocated in neuroblastomas with MYCN gene amplification, a subset of malignant melanomas, and in a newly delineated deletion syndrome. Here we report that the p36.3 region of human chromosome 1 consists of two identical genomic regions, each of which contain a Cdc2L gene linked to a metalloprotease (MMP) gene in a tail-to-tail configuration. This duplicated genomic region is also linked tightly to D1Z2, a genetic marker containing a highly polymorphic VNTR (variable number tandem repeat) consisting of an unusual 40-bp reiterated sequence. Thus, these genes and the polymorphic marker D1Z2 are organized as follows: telomere-D1Z2-5Ј-MMP22-3Ј-3Ј-Cdc2L2-5Ј-5Ј-Cdc2L1-3Ј-3Ј-MMP21-5Ј-centromere. Remarkably, the introns and exons of Cdc2L1 and Cdc2L2, as well as their flanking regions, are essentially identical. A total of 15 amino acid differences, 12 nonconservative and 3 conservative, can be found in the 773-786 amino acids specified by the various products of the Cdc2L genes. Two separate promoter/5Ј untranslated (UT) regions, CpG1 and CpG2, are identical to a reported previously methylated genomic CpG sequence and are used to express >20 different Cdc2L transcripts from the two genes. The expression of CpG2 transcripts from Cdc2L1 and Cdc2L2 is tissue/cell-line specific. CpG1 transcripts are expressed ubiquitously from both genes, with perhaps some bias towards the expression of CpG1 Cdc2L1 mRNAs in certain hematopoietic cells.[The sequence data described in this paper have been submitted to the GenBank data library under the following accession nos.: (cDNAs) AF067511-AF067529; (genomic) AF080678-AF080697.]The human Cdc2L1 and Cdc2L2 genes were localized previously to chromosome band 1p36.3, and they are deleted/altered frequently in neuroblastomas with amplified MYCN genes, a subset of malignant melanoma, and a 1p36 deletion disorder Shapira et al. 1997;Nelson et al. 1998). In fact, these genes are in close proximity to p73, which like Cdc2L1/2 is located proximally to D1Z2 (Kaghad et al. 1997). The Cdc2L1/2 genes express >20 distinct PITSLRE protein kinase isoforms, many arising by alternative splicing ; this study). Indirect immunofluorescence has demonstrated that the larger p110 PITSLRE isoforms expressed by Cdc2L1 and Cdc2L2 are localized in the nucleus, with a high concentration in nuclear speckles (Loyer et al. 1998). The cell cycle-regulated RNA-binding protein RNPS1 was isolated with the PITSLRE p110 isoforms by two-hybrid cloning (Loyer et al. 1998). Overexpression of RNPS1 in mammalian cells results in the redistribution of this kinase, RNPS1, and certain splicing components into fewer, and much larger, nuclear speckles. Treatment of the same mammalian cells with transcriptional inhibitors (e.g., H8, DRB) results in a...

show abstract

“…Analyses of gross structural rearrangement in the IDS region such as inversions and deletions suggest that these rearrangements are the consequence of both homologous and illegitimate (non-homologous) recombination [Bondeson et al, 1995b;Birot et al, 1996;Karsten et al, 1997;Bunge et al, 1998;Lagerstedt et al, unpublished results]. One of the most common rearrangements in the IDS region is a 40 kb inversion which is caused by homologous recombination between closely related sequences which are located in intron 7 of the IDS gene and in the IDS-2 locus [Bondeson et al, 1995b].…”

Section: Discussionmentioning

confidence: 96%

Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): Identification of a fusion transcript including sequences from the geneW and theIDS gene

Lagerstedt

Carlberg

Kariminejad³

et al. 2000

Hum. Mutat.

View full text Add to dashboard Cite

Two Distinct Deletions in theIDSGene and the GeneW: A Novel Type of Mutation Associated with the Hunter Syndrome

Cited by 25 publications

References 21 publications

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

Duplication of a Genomic Region Containing the Cdc2L1-2 and MMP21-22 Genes on Human Chromosome 1p36.3 and their Linkage to D1Z2

Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): Identification of a fusion transcript including sequences from the geneW and theIDS gene

Contact Info

Product

Resources

About

Two Distinct Deletions in theIDSGene and the GeneW: A Novel Type of Mutation Associated with the Hunter Syndrome

Cited by 25 publications

References 21 publications

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld s ) mouse

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld s ) mouse

Duplication of a Genomic Region Containing the Cdc2L1-2 and MMP21-22 Genes on Human Chromosome 1p36.3 and their Linkage to D1Z2

Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): Identification of a fusion transcript including sequences from the geneW and theIDS gene

Contact Info

Product

Resources

About

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse