Integration of physical, genetic and cytogenetic maps of human chromosome 7: isolation and analysis of yeast artificial chromosome clones for 117 mapped genetic markers

Abstract

An important goal for the human genome project is to assemble fully integrated physical, genetic and cytogenetic maps for each human chromosome. Towards that end, we have isolated yeast artificial chromosome (YAC) clones containing 117 of the 119 genetic markers that constitute a recently constructed, detailed genetic map of human chromosome 7. Analysis of these clones reveals numerous examples where adjacent genetic markers have been physically connected, either in individual YACs or in multi-YAC contigs. At present, the 117 genetic markers are contained in fewer than 80 YAC contigs, with most of these contigs uniquely ordered relative to one another based on the genetic map positions of the corresponding markers. These YACs and YAC contigs are estimated to contain approximately 60-85% of the DNA from human chromosome 7. YACs representing 36 genetic markers were mapped by fluorescence in situ hybridization (FISH) to metaphase chromosomes, allowing assignment of these genetic markers to cytogenetic bands along chromosome 7 and placement of the centromere within the genetic map. Together, these studies provide genetically and cytogenetically anchored YAC clones covering the majority of chromosome 7 that will be useful both for the positional cloning of genes and as a framework for assembling a complete YAC-based physical map of the chromosome.

Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour

“…The physical extent of the LOH in this tumour, therefore, extended from 7pter to 7p15 (Green et al, 1994;Tsui et al, 1995). Comparison of the PCR product from the constitutional versus the tumour DNA for locus D7S493 apparently reveals three bands in the constitutional DNA and two in the tumour DNA (Figure 1).…”

“…The physical location of the microsatellite markers used is shown in Table 2, and is derived from published data (Green et al, 1994;Tsui et al, 1995) as well as that presented at the most recent chromosome 7 workshop (SCW7.2). Not all of the markers used in this study have been assigned to a cytogenetic or radiation hybrid (RH) map (Green et al, 1994;Tsui et al, 1995). The optimal PCR conditions for each of the microsatellite primer pairs is also detailed in Table 2.…”

“…This data is perhaps best explained by the presence of an homozygous deletion for a region including D7S507 in GOS 44. The most recent chromosome 7 workshop (SCW 7.2) places D7S507 centromeric to D7S517 with a LOD score of 1000 : 1, and with a physical location of 7p15-21 (Green et al, 1994;Tsui et al, 1995). It would be unlikely for there to be retention of the D7S507 locus, when markers either side (D7S517 and D7S503) unequivocally show LOH, unless this tumour had a very complex and unusual chromosomal rearrangement.…”

“…It would be unlikely for there to be retention of the D7S507 locus, when markers either side (D7S517 and D7S503) unequivocally show LOH, unless this tumour had a very complex and unusual chromosomal rearrangement. The physical distance between D7S517 and D7S503 is approximately 21.3 cM (Green et al, 1994;Tsui et al, 1995). Clearly, further polymorphic loci mapping between D7S517 and D7S503 should be tested against tumour GOS 44 to de®ne the extent of the deleted region further.…”

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

“…At later stages, physical mapping incorporated STSs developed from available BACend sequence (TIGR Database; Table 1), as well as EST-derived STSs predicted to map to the SDS locus on GeneMap'99. 22 Based on integrated maps, 21,23,24 it was evident that the 2.7 cM SDS locus spanned the centromere of chromosome 7. As the interval was saturated with genetic markers, the question arose as to which markers flank the centromere on the p and the q arms.…”