Long-range map of a 3.5-Mb region in Xp11.23-22 with a sequence-ready map from a 1.1-Mb gene-rich interval.

Schindelhauer, Dirk; Hellebrand, Heide; Grimm, Lena Lisbeth; Bader, Ingrid; Meitinger, Thomas; Wehnert, Manfred; Ross, Mark T.; Meindl, Alfons

doi:10.1101/gr.6.11.1056

Cited by 32 publications

(16 citation statements)

References 47 publications

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“…The density of genes and ESTs analyzed in each interval on the chromosome (Fig. 1) largely reflects the distribution of genes on current transcript maps of the X chromosome (27) and accentuates particularly gene-rich regions such as Xp11 and Xq28 (28,29) and the gene-poor region Xq21 (30,31).…”

Section: Resultsmentioning

confidence: 91%

A first-generation X-inactivation profile of the human X chromosome

Carrel

Cottle

Goglin

et al. 1999

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

347

246

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In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing number of genes are known to ''escape'' X inactivation and are expressed from both the active (Xa) and inactive (Xi) X chromosomes; such genes reflect different molecular and epigenetic responses to X inactivation and are candidates for phenotypes associated with X aneuploidy. To identify genes that escape X inactivation and to generate a first-generation X-inactivation profile of the X, we have evaluated the expression of 224 X-linked genes and expressed sequence tags by reverse-transcription-PCR analysis of a panel of multiple independent mouse͞human somatic cell hybrids containing a normal human Xi but no Xa. The resulting survey yields an initial X-inactivation profile that is estimated to represent Ϸ10% of all X-linked transcripts. Of the 224 transcripts tested here, 34 (three of which are pseudoautosomal) were expressed in as many as nine Xi hybrids and thus appear to escape inactivation. The genes that escape inactivation are distributed nonrandomly along the X; 31 of 34 such transcripts map to Xp, implying that the two arms of the X are epigenetically and͞or evolutionarily distinct and suggesting that genetic imbalance of Xp may be more severe clinically than imbalance of Xq. A complete X-inactivation profile will provide information relevant to clinical genetics and genetic counseling and should yield insight into the genomic and epigenetic organization of the X chromosome.

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Section: Resultsmentioning

confidence: 91%

A first-generation X-inactivation profile of the human X chromosome

Carrel

Cottle

Goglin

et al. 1999

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

347

246

View full text Add to dashboard Cite

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“…Instability of repetitive DNA has been observed in plasmids, cosmids, and YACs (Neil et al 1990;Schindelhauer et al 1996). We therefore analyzed representation of ␣-satellite DNA in segment 1 of the human PAC library derived from an MboI partially digested, male genome (Ioannou et al 1994).…”

Section: Representative Subregions Of Dxz1mentioning

confidence: 99%

Evidence for a Fast, Intrachromosomal Conversion Mechanism From Mapping of Nucleotide Variants Within a Homogeneous α-Satellite DNA Array

Schindelhauer¹,

Schwarz²

2002

Genome Res.

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Assuming that patterns of sequence variants within highly homogeneous centromeric tandem repeat arrays can tell us which molecular turnover mechanisms are presently at work, we analyzed the ␣-satellite tandem repeat array DXZ1 of one human X chromosome. Here we present accurate snapshots from this dark matter of the genome. We demonstrate stable and representative cloning of the array in a P1 artificial chromosome (PAC) library, use samples of higher-order repeats subcloned from five unmapped PACs (120-160 kb) to identify common variants, and show that such variants are presently in a fixed transition state. To characterize patterns of variant spread throughout homogeneous array segments, we use a novel partial restriction and pulsed-field gel electrophoresis mapping approach. We find an older large-scale (35-50 kb) duplication event supporting the evolutionarily important unequal crossing-over hypothesis, but generally find independent variant occurrence and a paucity of potential de novo mutations within segments of highest homogeneity (99.1%-99.3%). Within such segments, a highly nonrandom variant clustering within adjacent higher-order repeats was found in the absence of haplotypic repeats. Such variant clusters are hardly explained by interchromosomal, fixation-driving mechanisms and likely reflect a fast, localized, intrachromosomal sequence conversion mechanism.

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“…These results were consistent with an unbalanced translocation involving a gene between OATL1 and OATL2, a region of approximately 4 Mb. To further narrow the interval we performed FISH on ASPS-1 and ASPS-6 using four cosmids (A02167, U164B6, B1125, I1135) from a previously established 1.1 Mb cosmid contig immediately centromeric to the region covered by OATL1 YAC2 (Schindelhauer et al, 1996). Bicolor interphase FISH experiments revealed three signals for probes A02167 and U164B6, and two signals for the centromere X-speci®c probe in the vast majority of cells analysed suggesting that, similar to OATL1, these loci were present on the der(17) in addition to the two normal X chromosomes ( Figure 3).…”

Section: Fish Analysis Of Xp11 Breakpointmentioning

confidence: 99%

The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25

et al. 2001

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Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identi®ed a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To de®ne the interval containing the Xp11.2 break, we ®rst performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identi®ed non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Ampli®cation of the 5' portion of cDNAs containing the 3' portion of TFE3 in two di erent ASPS cases identi®ed a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically signi®cant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBXlike domain that shows signi®cant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocationassociated sarcomas. Oncogene (2001) 20, 48 ± 57.

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Long-range map of a 3.5-Mb region in Xp11.23-22 with a sequence-ready map from a 1.1-Mb gene-rich interval.

Cited by 32 publications

References 47 publications

A first-generation X-inactivation profile of the human X chromosome

A first-generation X-inactivation profile of the human X chromosome

Evidence for a Fast, Intrachromosomal Conversion Mechanism From Mapping of Nucleotide Variants Within a Homogeneous α-Satellite DNA Array

The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25

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