X chromosome map at 75-kb STS resolution, revealing extremes of recombination and GC content.

Abstract

In addition to sustaining an exponentially increasing rate of gene finding (Collins 1995), yeast artificial chromosome/sequence-tagged site (STS/YAC)-based maps (Burke et al. 1987;Olson et al. 1989) have begun to reveal additional features of chromosome structure and dynamics. For example, during the development of maps for subportions of the X chromosome, the existence of a second "pseudoautosomal" region at the Xq terminus of the chromosome was demonstrated (Freije and Schlessinger 1992;Li and Hamer 1995), followed by the discovery that the region shows a unique phenomenon of gene inactivation on both the X and Y homologs (D'Esposito et al. 1996). In another instance, it was shown that a cluster of genes in a delimited segment of XpI 1 escape X inactivation (Miller et al. 1995). As the density of markers across the chromosome has increased beyond the 100-kb resolution goal suggested for the 1Corresponding author. E-MAIL davids@sequencer.wustl.edu; FAX (314) 362-3203."genome initiative," additional features are revealed, as described here.The average inter-STS distance of-75 kb has been achieved by the placement of 2091 STSs on cognate YACs across the 160 Mb of the chromosome. Collectively, the STSs sample -1% of Xspecific sequences. About half of the STSs (962) are made from YAC insert ends (Kere et al. 1992), and another 592 are from randomly derived unique Xchromosomal sequences. However, the STSs also include 97 expressed sequence tags (ESTs) and 190 gene-specific STSs from known genes, as well as 192 dinucleotide and 38 tri-and tetranucleotide repeat markers that detect polymorphism. As a result, the YAC/STS map can be integrated with transcriptional and genetic maps. RESULTS Mapping Strategy and PerformanceWe used a modified "all-walking" form of STS content mapping (Kere et al. 1992) in which STSs were

X-linked recessive inheritance of radial ray deficiencies in a family with four affected males

“…Our data indicate that DXS1212 is located telomeric of DXS1001. This is in accordance with data from Ge Âne Âthon and Nagaraja et al 7,11 Therefore, we choose the order DXS8067, DXS1001, and DXS1212 (Figure 1). The unaffected males II-5, and II-7 share part of the haplotype of the patients except for the region between DXS8055 and DXS1212 ( Figure 1).…”

“…According to the genetic map of the X chromosome of Marshfield, this interval is about 4.9 cM. According the genetic map of Ge Âne Âthon and that of Nagaraja et al, 7,11 this interval is about 16.2 cM. We performed mutation analysis for two candidate genes in this interval; the ZNF183 and IAP 3 genes and did not find a disease causing mutation in these genes.…”

High Throughput Fingerprint Analysis of Large-Insert Clones

“…We selected 17 STSs from the interval sWXD 1833-sWXD 1888 (Nagaraja et al 1997), which spans ∼1 Mb of the X chromosome. Thus, the average marker density across this interval was one marker per 58 kb.…”

“…Contig B's left-most clone is the BAC R038K21a. These two contigs are oriented according to the order of the STS markers (Nagaraja et al 1997). Thus, 0545D18a and R038K21a might overlap.…”

Toward a Complete Human Genome Sequence

“…The contigs were positioned using markers that were also present in the available genetic (Murray et al 1994;Dib et al 1996) or radiation hybrid (RH) maps of the human genome. The average STS spacing of these combined maps is ∼1/250 kb for the whole genome maps Hudson et al 1995), and up to 1/70 kb for selected single chromosomes (Chumakov et al 1992;Foote et al 1992;Collins et al 1995;Doggett et al 1995;Gemmill et al 1995;Krauter et al 1995;Bouffard et al 1997;Nagaraja et al 1997). Although long-range continuity was obtained with these maps, human YACs were not considered suitable substrates for large-scale genomic sequencing in general, because of the high degree of chimerism and the instability observed in a large proportion of the YAC clones (Green et al 1991;Nagaraja et al 1994).…”