A Radiation Hybrid Map of Human Chromosome 5 with Integration of Cytogenetic, Genetic, and Transcript Maps

Abstract

One of the major goals of the human genome project is to establish a physical map of each human chromosome with a density of sequence-tagged site (STS) markers exceeding one every 100 kb. We report here the generation of a human chromosome 5-specific radiation hybrid (RH) map that includes 556 markers. Of these markers, 132 loci are ordered with a maximum likelihood ratio of >1000:1 compared with the next most likely order. An additional 113 loci were ordered relative to these backbone markers with a maximum likelihood ratio of >10:1 but <1000:1. Together, these 245 loci form an ordered framework map for the chromosome. Using this framework, >300 more markers were localized based on two-point analysis with the ordered set. On average, there are 50 markers in common with the RH map presented here and other chromosome 5 maps included in the current whole genome cytogenetic, genetic, and physical maps. The accuracy of all the maps is evident in that there are no more than two discrepancies between any one of them and these data. All of the maps encompassing chromosome 5 complement each other providing excellent STS coverage with >2200 loci combined. The chromosome 5-specific RH map contains 20% of these independent loci. In addition, our RH map contains STSs derived from clones suitable for fluorescent in situ hybridization, allowing alignment to the cytogenetic map. Together, these maps will assist in the assembly of sequence-ready contigs and will aid in the identification of disease loci on chromosome 5 by positional cloning and positional candidate approaches.[The STS sequences described in this paper have been submitted to dbSTS under accession nos. G15666–G15715 andG16049–G16063. A complete map of human chromosome 5 is available as an on-line supplement at http://www.cshl.org/gr.]

miR-200a Inhibits Tumor Proliferation by Targeting AP-2γ in Neuroblastoma Cells

“…We have identified a novel target of miR200a, AP-2γ, a member of the developmentally regulated AP-2 transcription factor family that was originally identified from a MCF-7 cDNA library (McPherson et al, 1997). It is an important regulator of embryogenesis and tumor regenesis (Pellikainen et al, 2007).…”

“…To date, five members of the AP-2 family have been identified: AP-2α, AP-2β, AP-2γ, AP-2δ and AP-2ε (Eckert et al, 2005). To date, little is known on the interaction between AP-2 transcription factors and miR-200 family; AP-2γ is a member of the developmentally regulated AP-2 transcription factor family that was originally identified from a MCF-7 cDNA library (McPherson et al, 1997). It is an important regulator of embryogenesis and tumor regenesis (Pellikainen et al, 2007).…”

Extensive Conservation of Sex Chromosome Organization Between Cat and Human Revealed by Parallel Radiation Hybrid Mapping

“…Human and mouse maps, based on information from Lahn and Page (1997) and Mazeyrat et al (1998), are meant to be proportionate to intergenic spacing, yet they do not necessarily reflect true physical distances. McPherson et al 1997;Schmitt et al 1996) RH panels. Stewart et al (1997) observed the centiray-tokilobase ratio to be roughly half on the Y chromosome, likely because of the increased breakage frequency of the Y.…”

An Integrated Physical Map for the Short Arm of Human Chromosome 5

“…A direct comparison with radiation hybrid maps of 5p is also possible by use of markers shared by both studies (McPherson et al 1997). Whereas the experimentally determined linear order of markers is, in general, the same between the two maps, the number of markers on the physical map (Fig.…”

“…2) is nearly an order of magnitude greater. Like the genetic map, there is a greater than fivefold (14.8-81.5 cR/Mb observed, McPherson et al 1997) difference in the ratio of cR/Mb between various mapped markers, making direct comparisons imprecise. In the few cases in which radiation hybrid mapping could split markers that physical mapping could not (i.e., 675,405,5pC; 502,648 5pI; 663,426 5pM), this information did not assist in the unambiguous definition of the STS order.…”