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The physical locations on human metaphase chromosomes of over 950 yeast artificial chromosome (YAC) clones from the CEPH library have been determined by fluorescence in situ hybridization and described as fractional chromosome length relative to the terminus of the short arm. Collectively, these clones contain approximately 1 billion basepairs of human DNA, about one-third of the human genome. In addition, the locations of 337 of these clones were established in terms of cytogenetic bands for chromosomes 1-18, 20, and X. Since most clones are positive for one or more of the Généthon polymorphic STS markers with defined genetic linkage distances corresponding to their physical locations, these data facilitate the integration of the cytogenetic, genetic, and physical maps of the human genome. Use of these mapping data in conjunction with public database information on CEPH YACs greatly facilitates the identification of YACs or polymorphic markers at specific locations in the genome.

The host resistance locus Bcg determines resistance of mice to infection with intracellular pathogens such as certain species of Mycobacteria, Salmonella typhimurium, and Leishmania donovani. Bcg maps on the proximal portion of mouse chromosome 1, very tightly linked to villin (Vil), with the gene order and intergene distances Tp-1-(1 cM)-D1Mcg105-(0.1 cM)-lambda Mm1C165/Vil/Bcg-(0.2 cM)-lambda Mm1C136-(0.3 cM)-Des-(0.1 cM)-Inha. In an effort to clone genomic sequences overlapping Bcg, we have used pulsed-field gel electrophoresis (PFGE) and fluorescence in situ hybridization to construct a physical map of the 3.9-Mb segment of proximal mouse chromosome 1, near Bcg. In situ hybridization to metaphase mouse chromosomes indicates that the mapped region is within band C5. Physical mapping of the Tp-1-Vil and lambda Mm1C136-Inha intervals was carried out by PFGE analysis, whereas the Vil-Des interval was estimated by in situ hybridization to interphase nuclei. Results of these combined analyses indicate the following locus order and maximal interlocus distances: Tp-1-(1000 kb)-D1Mcg105-(160 kb)-lambda Mm1C165-(180 kb)-Vil-(800 kb)-lambda Mm1C136-(290 kb)-Des-(130 kb)-Inha. Detailed restriction mapping of this region identifies numerous putative CpG islands, suggesting that several transcription units are present in the vicinity of Bcg.

Neurotensin (NTS) is an endogenous tridecapeptide of the central nervous system and the gastrointestinal tract of different mammalian species including human. The human gene encoding neurotensin has previously been assigned to chromosome 12 but no regional localization was available. We now confirm this assignment and place the NTS gene on the physical and cytogenetic maps. The NTS gene is located on a yeast artificial chromosome contig that contains several polymorphic markers and is close to a polymorphic marker located at 95.8 cM on the Généthon linkage map. NTS is immediately proximal to four polymorphic markers, including D12S81 (AFM102xg9) and D12S88 (AFM158yb4). Using fluorescence in situ hybridization, we map the gene cytogenetically to band 12q21.

ASCL1, the human achaete-scute homolog, is a helix-loop-helix transcription factor that was previously assigned to chromosome 12 using a rodent-human somatic hybrid panel. We now placed this gene on a yeast artificial chromosome contig encompassing position 119 cM of the Généthon genetic map between the two genes phenylalanine hydroxylase (PAH) and tumor rejection antigen 1 (TRA1). We also localized ASCL1 in the 12q22-q23 cytogenetic interval by using fluorescence in situ hybridization.