A hypervariable region at the D19S11 locus

Summary The polymorphic locus D19S11 consists of four closely linked RFLPs: , , and on chromosome 19p13.219cen, revealed by subclones p13-1-82 and p13-2-21 from cosmid 1–13. Here, we report that p13-1-25, an additional subclone of c1-13, reveals three insertion/deletion RFLPs, , , and , at the D19S11 locus. In situ hybridization of p13-1-25 to metaphase chromosomes from a carrier of a 19/X translocation with a breakpoint near the centromere confirms localization of D19S11 to 19p. Studies with hydatidiform moles have generated assignments of specific restriction fragments to these three loci, and genotypic studies in three-generation families have indicated that they are closely linked. Loci (also detected by p13-1-82) and each have but two common alleles, whereas has at least 33 alleles, including a null allele. Fifty unrelated individuals tested displayed unique fragment patterns on Taq I blots probed with p13-1-25. Applications of this probe include monitoring loss of chromosome 19 during tumorigenesis, monitoring engraftment of donor bone marrow after transplantation, testing for paternity, and mapping disease genes on chromosome 19.     

Expression map of human chromosome region 17p13.3, spanning the RP13 dominant retinitis pigmentosa locus, the Miller-Dieker lissencephaly syndrome (MDLS) region, and a putative tumour suppressor locus

Chromosome region 17p13.3 is rich in genes, with 223 expressed sequence tags (ESTs) within the last 15 cM (7 Mb) of chromosome 17p in the GeneMap database. Loci for dominant retinitis pigmentosa (RP13), central areolar choroidal dystrophy (CACD), anterior polar cataract (CTAA2), Miller-Dieker lissencephaly syndrome (MDLS), and a region of tumour loss of heterozygosity (LOH) distinct from TP53 all map into the region adjacent to the 17p telomere. To date, however, there is no physical map of the region, which has resisted the efforts of the CEPH and Whitehead physical mapping programmes to generate contiguous clones across it. We have created a physical map covering approximately 3.5 Mb (6 cM)in this region, spanning the RP13 interval and extending distally to the gene MDCR (formerly, LIS1), which, when deleted, leads to the MDLS phenotype. The region covered is also the point of maximum LOH in lung cancer and has been implicated in the pathogenesis of many other human cancers. The map orders 47 sequence tagged sites, including 32 genes or ESTs, nine genetic markers, four anonymous sequences, and two YAC end clones, and highlights new candidate ESTs for involvement in RP13, MDLS, CTAA2, and a tumour-susceptibility gene.     

Localization of the Miller-Dieker critical region is proximal to locus D17S34 (p144D6) in 17p13.3

A child with normal growth and development and the abnormal karyotype 46,XY,17ps, was analyzed using molecular probes localized to 17p13. The results indicated the presence of two copies of the probes YNZ22.1 (D17S5) and YNH37.3 (D17S28), previously shown to be deleted in all Miller-Dieker (MDS) patients studied. However, the patient was hemizygous for probe p144D6 (D17S34), which is absent in approximately 75% of the MDS patients. As the patient is active at 9 months of age, with no clinical signs of MDS, the results confirm that the absence of locus D17S34 does not lead to the phenotypic expression of MDS. Furthermore, this deletion should assist in defining the distal limits of this contiguous gene syndrome.     

A physical map of the human pseudoautosomal region.

A physical map of the human pseudoautosomal region has been constructed using pulsed field gel electrophoresis and the infrequently cutting restriction enzymes BssHIII, EagI, SstII, NotI, MluI and NruI. This map extends 2.3 Mbp from the telomere to sex-chromosome-specific DNA, includes at least seven CpG islands and locates four genetically mapped loci. Five of the CpG islands are organized into two clusters. One cluster is adjacent to the telomere, the other extends into sex-chromosome-specific DNA. There is congruence between the genetic and physical maps which implies that the frequency of recombination is approximately uniform throughout the DNA.     

A physical map of a 1.3-Mb region on the long arm of chromosome 12, spanning the GLI and LRP loci.

We have used pulsed-field gel electrophoresis to construct a long-range restriction map spanning more than 1.3 million bp of the q13-q14 segment of chromosome 12. Within this region lie the genes coding for the gli oncogene and the low-density lipoprotein receptor-related protein (LRP). The distance between the genes is about 200-300 kb. We also observe a methylation-free island 3' to the LRP gene.     

A 14-Mb physical map of the region at chromosome 11q13 harboring the MEN1 locus and the tumor amplicon region.

We have constructed a physical map of chromosome 11q13, using 54 DNA markers that had been localized to 11q13.1----q13.5 by means of somatic hybrid cell panels. Although the map has some gaps, it spans nearly 14 Mb and includes the region containing the gene responsible for multiple endocrine neoplasia type 1 (MEN1) and also the region that is amplified in several types of malignant tumors. As the estimated average distance between each locus is roughly 300 kb, the markers reported here will be valuable resources for construction of contig maps with yeast artificial chromosomes and/or cosmid clones. Furthermore, these clones will be useful in efforts to identify the MEN1 gene and in analyses of the amplification units present at 11q13 in certain tumors.     

Construction of a long-range YAC physical map spanning the 10-cM region between the markers D18Mit109 and D18Mit68 on mouse proximal chromosome 18.

Four yeast artificial chromosome (YAC) contigs, physically approximately 8 Mb, have been constructed spanning a 10-cM region on mouse proximal chromosome 18 and include the sites of 21 known genes, including those near the twirler (Tw) locus and the recently isolated Niemann-Pick type C1 (npc1) gene, formerly designated as the spm locus. This physical map consists of 49 YAC clones that cover roughly 15% of the chromosome. The physical order of 38 microsatellite sequence-tagged sites (STSs) could be assembled and confirmed based on their presence or absence in individual YACs, from proximal D18Mit109 through distal D18Mit68. These YACs provide an important resource for the further characterization and identification of known and unknown genes. The physical map has been integrated with our previously published genetic linkage map and showed an average genetic to physical distance of cM/Mb > 1.1.     

A genetic linkage map of five marker loci in and around the Duchenne muscular dystrophy locus

Linkage analysis of five marker loci in and around the Duchenne muscular dystrophy (DMD) locus, DXS84, DXS206, DXS164, DXS270, and DXS28, was conducted with 499 families. Overall, the best multipoint distances were found to be DXS84-3.7 +/- 0.6 cM-DXS206-1.0 +/- 0.4 cM-DXS164-1.9 +/- 0.6 cM-DXS270-12.0 +/- 1.1 cM-DXS28. A comparison of this linkage map with the established physical map suggests the presence of hot spots for recombination in the DMD locus.     

A 2-Mb YAC/BAC-based physical map of the ovum mutant (Om) locus region on mouse chromosome 11

The embryonic lethal phenotype observed when DDK females are crossed with males from other strains results from a deleterious interaction between the egg cytoplasm and the paternal pronucleus soon after fertilization. We have previously mapped the Om locus responsible for this phenotype, called the DDK syndrome, to an approximately 2-cM region of chromosome 11. Here, we report the generation of a physical map of 28 yeast and bacterial artificial chromosome clones encompassing the entire genetic interval containing the Om locus. This contig, spanning approximately 2 Mb, was used to map precisely genes and genetic markers of the region. We determined the maximum physical interval for Om to be 1400 kb. In addition, 11 members of the Scya gene family were found to be organized into two clusters at the borders of the Om region. Two other genes (Rad51l3 and Schlafen 2) and one EST (D11Wsu78e) were also mapped in the Om region. This integrated map provides support for the identification of additional candidate genes for the DDK syndrome.     

A physical map of the Q region of B10.P

The murine class I MHC Q region is part of a large complex multigene family whose members have various peptide-binding functions. The structure of the Q region is complex, varying extensively in the b, d, k, and q haplotypes so far examined. To better understand the structural heterogeneity, we examined the Q region of B10.P, a strain whose immunological characteristics are distinct from other haplotypes. A total of 89 cosmids were isolated from genomic DNA. The B10.P Q region was found to contain seven genes in a 190-kb cluster linked to D^p and two additional Q genes in a separate 55-kb cluster. The gene arrangement in this haplotype was unique and did not correspond to any other haplotype; this underscores the complexity of chromosomal structure in this region. In addition to the Q region clusters, Tla region was tentatively aligned in five clusters spanning approximately 300 kb. One 37-kb M region cosmid was also identified. Received: 24 February 1995 / Accepted: 10 October 1995     

Detailed physical and genetic mapping in the region of plasminogen,D17Rp17e,and quaking

We present here a detailed physical map encompassing over 600 kb of mouse Chromosome (Chr) 17 in the region of plasminogen, D17Rp17e, and quaking. This region is cloned in yeast artificial chromosomes (YACs). We have identified several CpG islands within this region from pulsed field gel mapping of mouse genomic DNA and YAC DNA. Five new DNA probes have been generated. One, D17Leh514, is a minimum of about 90 kb distal to plasminogen. Four, D17Leh513, D17Leh512, D17Leh511, and D17Leh510, are proximal to D17Rp17e, the closest previously described genetic marker to quaking^viable and quaking^lethal-1 mutations. We have genetically mapped D17Leh511 to within 0.15 cM of these mutations. The genetic distance to D17Rp17e from D17Leh511 is also 0.15 cM; the physical distance of less than 360 kb (minimum 200 kb) is consistent with an approximation of 2 Mbp per cM.     

A physical map of the bioAB region in the lambda bio transducing phage

The center of the pBopA promoter-operator region for the bioABFCD operon is located 1.71 kb clockwise from the att lambda site on the Escherichia coli genome, as determined by the position of the p131 (IS1) insertion. The order of several bio endpoints to the right of p131 is lambda bio267, 122, 169, 74, 1, and 69. The endpoints of the two bio deletions, delta 61 in bioA and delta 3h in bioB, were also determined.     

A multiple interval physical map of the pericentromeric region of human chromosome 10

Five intervals in the pericentromeric region of human chromosome 10 have been defined using a panel of somatic cell hybrids carrying portions of the chromosome. The map positions of twelve markers, consisting of four genes and eight anonymous DNA segments, have been localized by assignment to one of the five intervals. Several other markers could be placed in specific intervals by genetic linkage to assigned loci. When previously published data are incorporated, the summary map of the pericentromeric region encompasses thirty-two loci in bands 10p11.2-q11.2.