A genetic linkage map of 96 loci on the short arm of human chromosome 3.

We constructed a genetic map of 96 loci on the short arm of human chromosome 3 (3p) in 59 families provided by the Centre d'Etude du Polymorphisme Humaine (CEPH). Twenty-nine continuously linked loci were placed on the map with likelihood support of at least 1000:1; one locus, D3S213, was placed on the map with likelihood support of 871:1; D3Z1, an alpha satellite centromeric repeat probe, was placed on the map with likelihood support of 159:1; 65 loci were assigned regional locations. The average heterozygosity of the uniquely ordered markers was 49%. The map extends from 3p26, the terminal band of 3p, to the centromere (from D3S211 to D3Z1). Multipoint linkage analysis indicated that the male, female, and sex-averaged maps extend for 102, 147, and 116 cM, respectively. The mean genetic distance between uniquely ordered loci on the sex-averaged map was 4.0 cM. Probe density was greatest for the region of 3p between D3F15S2e and the telomere. The sex-averaged map contained two intervals greater than 10 cM. Seventeen probes were localized by fluorescence in situ hybridization. The loci described in this report will be useful in building an integrated genetic and physical map of this chromosome.     

A centromere-based linkage group on the long arm of human chromosome 17

A genetic linkage group on the long arm of chromosome 17 is reported. A maximum likelihood of theta = 0.20 between the centromere-based locus D17Z1 and COL1A1 has been found, as well as a theta = 0.10 between COL1A1 and GH1. The most likely order of the three loci is D17Z1-COL1A1-GH1.     

A genetic linkage map of the long arm of human chromosome 22

We have used a recombinant phage library enriched for chromosome 22 sequences to isolate and characterize eight anonymous DNA probes detecting restriction fragment length polymorphisms on this autosome. These were used in conjunction with eight previously reported loci, including the genes BCR, IGLV, and PDGFB, four anonymous DNA markers, and the P1 blood group antigen, to construct a linkage map for chromosome 22. The linkage group is surprisingly large, spanning 97 cM on the long arm of the chromosome. There are no large gaps in the map; the largest intermarker interval is 14 cM. Unlike several other chromosomes, little overall difference was observed for sex-specific recombination rates on chromosome 22. The availability of a genetic map will facilitate investigation of chromosome 22 rearrangements in such disorders as cat eye syndrome and DiGeorge syndrome, deletions in acoustic neuroma and meningioma, and translocations in Ewing sarcoma. This defined set of linked markers will also permit testing chromosome 22 for the presence of particular disease genes by family studies and should immediately support more precise mapping and identification of flanking markers for NF2, the defective gene causing bilateral acoustic neurofibromatosis.     

A multipoint linkage map of the distal short arm of the human X chromosome.

The distal portion of the short arm of the human X chromosome (Xp) exhibits many unique and interesting features. Distal Xp contains the pseudoautosomal region, a number of disease loci, and several cell-surface markers. Several genes in this area have also been observed to escape X-chromosomal inactivation. The characterization of new polymorphic loci in this region has permitted the construction of a refined multipoint linkage map extending 15 cM from the Xp telomere. This interval is known to contain the loci for the diseases X-linked ichthyosis, chondrodysplasia punctata, and Kallmann syndrome, as well as the cell-surface markers Xg and 12E7. This region also contains the junction between the pseudoautosomal region and strictly X-linked sequences. The locus MIC2 has been demonstrated by linkage analysis to be indistinguishable from the pseudoautosomal junction. The steroid sulfatase locus has been mapped to an interval adjacent to the DXS278 locus and 6 cM from the pseudoautosomal junction. The polymorphic locus (STS) DXS278 was shown to be informative in all families studied, and linkage analysis reveals that the locus represents a low-copy repeat with at least one copy distal to the STS gene. The generation of a multipoint linkage map of distal Xp will be useful in the genetic dissection of many of the unique features of this region.     

A genetic linkage map of 27 loci from PND to FY on the short arm of human chromosome I.

A genetic linkage map of 27 loci on the short arm of human chromosome 1 has been developed by analysis of the 40 families in the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel. Probes that recognize 14 novel RFLPs at loci designated D1S9-D1S22 were isolated from a flow-sorted chromosome 1 library. A linkage map of chromosome 1p was constructed from the genotypic data at these 14 loci, RFLPs at eight cloned genes (PND, ALPL, FUCA1, SRC2, MYCL, GLUT, TSHB, and NGFB), two previously identified RFLPs (D1S2 and D1S57), two blood group antigens (RH and FY), and the isozyme PGM1. All 27 loci form a continuous linkage group, from FY to PND, of 102 cM in males and 230 cM in females. This map provides a basis for highly informative multipoint mapping studies for most of the short arm of chromosome 1.     

A physical map of the human Y-chromosome short arm

A physical map of the Y-chromosome short arm was constructed using DNA probes p19B, Y-286/la5, pZFY, Y-280, and Y-227. These probes hybridize with four NotI fragments of 400 kb (p19B and Y-286/la5), 350 kb, 1.9 Mb, and 3.0 Mb, respectively. The restriction fragments were shown to be adjacent to each other by analysis of NotI partial digests, overlapping restriction fragments, and/or the detection of rearranged restriction fragments in a 46,XX male. The present map covers approximately 5.6 Mb of contiguous DNA of Yp. Previously, the size of the pseudoautosomal region was estimated to be 2.3 Mb, and a 5.3-Mb NotI fragment containing Y-specific repeated DNA was assigned to proximal Yp. These and the present data account for approximately 13 Mb and thus for most of the DNA content of the Y short arm.     

A detailed genetic map of the long arm of chromosome 11

We describe 14 new restriction fragment length polymorphisms, corresponding to 13 loci on the long arm of chromosome 11. A detailed genetic map of chromosome 11q has been constructed from these and other loci (a total of 31 loci) typed in 59 reference families. The 23 most informative markers were selected to establish a map with a strongly supported order; regional localizations are provided for eight other markers. The loci span 88 cM in males and 148 cM in females and form a dense continuum on 11q. These ordered polymorphic markers will be of help in studying the genes responsible for several diseases that have been localized to this region, including genes responsible for multiple endocrine neoplasia type I (MEN1), ataxia telangiectasia (AT), tuberous sclerosis (TSC), and some forms of asthma and rhinitis.     

On the genetic length of the short arm of the human X chromosome

Published estimates of the length of the human X chromosome are unreliable because they are based on scanty linkage data and complex assumptions about the frequency and distribution of chiasmata in female meiosis. In recent months we have established linkage between restriction fragment length polymorphisms (RFLPs) and several genes on the short arm of the X chromosome. These and previous data can be combined to construct a continuous linkage map spanning the short arm from the Xg gene to the centromere. They suggest that the genetic length of the Xg-Xcen segment may be in the order of 75-90 cM.     

A fine structure physical map of the short arm of chromosome 5.

A series of somatic cell hybrids that retain abnormal chromosomes 5 from 11 different persons with deletions or translocations involving 5p have been isolated. One hundred twenty DNA fragments isolated from a genomic library enriched for sequences from 5p were regionally localized by Southern blot analysis of the hybrid cell deletion mapping panel, including five DNA fragments that reveal restriction fragment length polymorphisms. The fine structure physical map of 5p together with the identification of additional polymorphic loci will facilitate the construction of a complete linkage map of this region. In addition, DNA fragments localized to a region near the 5p15.2-5p15.3 border, which appears to be the segment of 5p that is critical in producing the phenotype associated with the cri du chat syndrome when it is rendered hemizygous by deletion, will be useful in a molecular and DNA level analysis of this deletion syndrome.     

A physical and genetic linkage map of the distal long arm of human chromosome 5.

By in situ hybridization of probes for three cloned genes and eight genetically-linked polymorphic DNA markers, we have prepared a physical map of the distal long arm of chromosome 5. These results, together with the localizations of 11 genes and the genetic linkage map reported previously by us and by other investigators, represent a map that spans 55 cM.     

A physical map around the WAGR complex on the short arm of chromosome 11

A long-range restriction map of part of the short arm of chromosome 11 including the WAGR region has been constructed using pulsed-field gel electrophoresis and a number of infrequently cutting restriction enzymes. A total of 15.4 Mbp has been mapped in detail, extending from proximal 11p14 to the distal part of 11p12. The map localizes 35 different DNA probes and reveals at least nine areas with features characteristic of HTF islands, some of which may be candidates for the different loci underlying the phenotype of the WAGR syndrome. This map will furthermore allow screening of DNA from individuals with WAGR-related phenotypes and from Wilms tumors for associated chromosomal rearrangements.     

Mapping the short arm of human chromosome 16

Physical mapping of 13 different breakpoints on the short arm of chromosome 16 using previously mapped probes and the subsequent mapping of additional probes enabled the division of this portion of the chromosome into six different intervals. D16S94 was mapped between HBA and D16S80 and is closer to PKD1 than either HBA or D16S80. A tight linkage group which includes FRA16A, D16S8, and D16S79 was identified. Seven breakpoints, including FRA16A, could not be separated by probe localizations. This study provides the basis for the development of detailed maps of the short arm of chromosome 16.     

A genetic map of human chromosome 17p

A genetic linkage map was constructed with 18 loci from the short arm and pericentric region of chromosome 17 typed on the CEPH reference families. The genetic map includes three markers extracted from the CEPH public database. Nine loci could be ordered using a threshold of odds of at least 1000:1 against alternative orders during the map construction process. With a reduced tolerance of 100:1, a total of 13 loci could be placed on the map spanning a distance of approximately 60 cM in females and 46 cM in males. There were statistically significant differences between the male and the female genetic maps. The order inferred from the genetic data was consistent with the physical localizations of these probes obtained from somatic cell hybrids and tumor deletion studies. This map should be useful for genetic fine mapping of 17p loci.     

A long range restriction map of the distal human X chromosome short arm around the steroid sulfatase locus.

The distal short arm of the human X chromosome is of interest because it contains genes which escape X chromosome inactivation and because it is subject to frequent deletions in human patients. The steroid sulfatase gene has been particularly well studied as an example of a gene which escapes X inactivation and which is included in a number of these deletion events. For these reasons a physical map of the region around the STS gene would be of interest. We have constructed a rare cutting enzyme map of this area and have determined the position of several nearby markers with respect to STS. We have also oriented the 5' and 3' ends of the STS gene on this map and have determined the centromeric and telomeric portions of the region. Finally, we have shown that this map can be used to locate deletion breakpoints in STS deficient patients.     

A refined physical map of the long arm of human chromosome 16

Mapping of 33 anonymous DNA probes and 12 genes to the long arm of chromosome 16 was achieved by the use of 14 mouse/human hybrid cell lines and the fragile site FRA16B. Two of the hybrid cell lines contained overlapping interstitial deletions in bands q21 and q22.1. The localization of the 12 genes has been refined. The breakpoints present in the hybrids, in conjunction with the fragile site, can potentially divide the long arm of chromosome 16 into 16 regions. However, this was reduced to 14 regions because in two instances there were no probes or genes that mapped between pairs of breakpoints.     

Ornithine aminotransferase-related sequences map to two nonadjacent intervals on the human X chromosome short arm.

Using a panel of human/rodent somatic cell hybrids segregating human X/autosome translocations and deletions, we have refined the localization of the X-linked sequences homologous to ornithine-delta-aminotransferase (OAT), the structural locus for which (OAT) maps to chromosome 10. OAT-related ("-like") (OATL) sequences mapped to two nonadjacent intervals: OATL1 mapped to Xp11.3-p11.23, while OATL2 mapped to Xp11.22-p11.21. X-linked OATL1 sequences polymorphic for ScaI and StuI map to the more distal interval in Xp11.3-p11.23. These results should help guide long-range cloning and mapping studies, as well as refine the genetic linkage map in this region of the X chromosome.     

Identification of two human ferritin H genes on the short arm of chromosome 6

We have found by analyses of human-hamster hybrid cells that two human ferritin H genes lie near the locus of the iron storage disease idiopathic hemochromatosis on chromosome 6p. One of these genes was isolated and shown to be a processed pseudogene. Comparison of its sequence with those of other ferritin H pseudogenes indicates that they may be derived from a functional H gene other than that on chromosome 11.     

Localization of HLA on the short arm of chromosome 6

Summary A detailed marker gene study in a large Dutch kindred segregating for a reciprocal translocation between the chromosomes 6 and 20, t(6;20) (p21;p13), revealed a close linkage between the HLA genes and the breakpoint on the short arm of 6. During this study an apparent peak lod score of 2.9 was obtained at a recombination value of 0.05 for a linkage between HLA and the breakpoint, indicating that the chromosomal region, carrying the HLA genes, is situated near the breakpoint in band 6p21 close to the transition to 6p22.     

A primary genetic linkage map for human chromosome 12

A primary genetic map for human chromosome 12 has been constructed from data on 23 restriction fragment length polymorphic systems collected in 38 normal families with large sibships. Linkage analysis of the genotypic data has ordered 16 loci into a continuous genetic map of 111 cM in males and 258 cM in females. Although most of the genetic map reflects a higher rate of recombination in females relative to males, significantly more frequent recombination was observed in males than in females in intervals between loci on the distal portion of the short arm of the chromosome. The mapping data shown here will serve as a first step toward a high-resolution genetic map for human chromosome 12.