A High-Resolution Radiation Hybrid Map of the Human Genome Draft Sequence

We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The −2log 10 P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with −log 10 P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome.

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“…1) [13][14][15] . When X-rays are used to randomly cleave DNA, neighboring markers are rarely separated, allowing linkage to be evaluated.…”

mentioning

confidence: 99%

Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids

et al. 2008

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“…Both publicly available 22,39 and our own mapping data position TPST1 unambiguously within the SDS critical region (Figure 3), with no evidence of duplication locally or elsewhere in the genome. Broad tissue distribution of TPST1 mRNA (Northern blot analysis in Ouyang et al 5 ) is consistent with multi-organ defects observed in SDS.…”

Section: European Journal Of Human Geneticsmentioning

confidence: 99%

Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene

et al. 2002

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Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterised by exocrine pancreatic dysfunction, haematological and skeletal abnormalities. We have previously defined the SDS locus as a 2.7 cM interval spanning the centromere of chromosome 7. To facilitate additional analysis of this complex and poorly characterised region, a framework of ordered genetic markers at 7p11-q11, including six newly identified, has been constructed using somatic cell, radiation hybrid and STS-content mapping. We have identified shared disease haplotypes, that recur in unrelated families of common ethnic origin, and extend across the SDS locus. Detection of ancestral and intrafamilial recombination events in patients refined the SDS locus to a 1.9 cM interval at 7q11, which contains the tyrosylprotein sulfotransferase 1 (TPST1) gene. Patients with SDS were screened for mutations in TPST1 by sequencing of exons and intron ± exon junctions. Two single nucleotide polymorphisms, but no disease-causing mutations, were identified. In addition, Southern blot analysis yielded no evidence of large-scale mutations, and RT ± PCR analysis failed to detect alterations in expression. These results exclude TPST1 as the causative gene for SDS. The established map of the refined SDS locus will assist in the identification and characterisation of other candidate genes for SDS.

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“…We have used the Genethon 10 , Marshfield 11 and deCODE 12 microsatellite-based maps, GeneMap99 13 and TNG 14 radiation hybrid maps, the Whitehead yeast artificial chromosome (YAC)-based map and the BAC physical map 4 to evaluate the completeness and order of assembled sequences for chromosomes 2 and 4. Only a small number (,1%) of sequence-tagged sites (STSs) were not identified in the existing sequence; these included STSs from repetitive sequences, sequence polymorphisms and regions within known sequence gaps.…”

Section: Comparison To Physical and Genetic Mapsmentioning

confidence: 99%