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 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 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.     

Interstitial deletion of the long arm of chromosome 11

A female patient with an interstitial deletion of the long arm of chromosome 11 is described. Her growth and psychomotor development were normal. She showed some facial dysmorphic features including cleft lip/palate, a probable cardiac defect and a triphalangeal thumb. A clinical correlation with similar cases is presented.     

A centromere-based genetic map of the short arm of human chromosome 6

A genetic map of the short arm of chromosomes 6 (6p) has been constructed with 20 genetic markers that define 16 loci, including a locus at the centromere. The 40 CEPH families and, for 4 loci, 13 additional Utah families were genotyped. All 16 loci form a single linkage group extending from near the telomeric region to the centromere, covering 159 cM (Haldane) on the female map and 94 cM on the male map. Sex differences in recombination frequencies are noted for the 6p map, with an excess occurring in males at the distal end. The genetic order of loci is consistent with their physical localization on 6p. Proximal to the three most distal loci on the map, markers are especially dense, providing an extended region on 6p useful for localizing genes of interest.     

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.     

A molecular genetic map of the long arm of chromosome 6R of rye incorporating the cereal cyst nematode resistance gene, CreR

 A genetic map of the long arm of chromosome 6R of rye was constructed using eight homoeologous group-6 RFLP clones and five PCR markers derived from the rye-specific dispersed repetitive DNA family, R173. The map was developed using a novel test-cross F₁ (TC-F₁) population segregating for resistance to the cereal cyst nematode. Comparisons were made between the map generated with other rye and wheat group-6 chromosome maps by the inclusion of RFLP clones previously mapped in those species. Co-linearity was observed for common loci. This comparison confirmed a dramatic reduction in recombination for chromosome 6R in the TC-F₁ population. The CreR locus was included in the linkage map via progeny testing of informative TC-F₁ individuals. CreR mapped 3.7 cM distal from the RFLP locus, XksuF37. Comparative mapping should allow the identification of additional RFLP markers more closely linked to the CreR locus. Received: 14 April 1998 / Accepted: 29 April 1998     

Partial deficiency of long arm of chromosome No. 11.

A child is presented with slight psychomotor retardation and few minor anomalies, in whom the cytogenetic analysis revealed a de novo translocation between the long arms of chromosomes 8 and 11, with deficiency of a small distal segment of 11q.     

A detailed multipoint gene map of chromosome 1q

Utilizing genotyping data for 23 markers, we have constructed a 21-locus multipoint genetic map of the long arm of chromosome 1. Five new RFLPs are reported. The map integrates anonymous loci from previous primary linkage maps and incorporates markers for 10 coding sequences. These markers form a continuous linkage group of 85 cM in males and 141 cM in females. The map was constructed employing the LINKAGE and CRIMAP computational methodologies via a stepwise algorithm.     

Radiation hybrid map of 13 loci on the long arm of chromosome 5.

Radiation hybrid mapping was used in conjunction with a natural deletion mapping panel to predict the order of and distance between 13 loci in the distal portion of the long arm of human chromosome 5. A panel of irradiation hybrids containing fragments of 5q was generated from an HPRT+ Chinese hamster-human cell hybrid containing a derivative chromosome 5 [der(5)t(4;5)(5qter----5p15.1::4p15.1----4pter)] as its only human DNA. One hundred nine radiation hybrids containing human DNA were screened with polymerase chain reaction primer sets representing nine genes encoding growth factors, growth factor receptors, or hormone receptors (IL3, IL4, IL5, CSF1R, FGFA, ADRB2, GRL, GABRA1, and DRD1) as well as four other loci (FER, SPARC, RPS14, and CD14) to generate a radiation hybrid map of the area 5q21-q35. A physical map predicting the order of and distance between the 13 loci was constructed based on segregation of the 13 loci in hybrid clones. The radiation hybrid panel will be useful as a mapping tool for determining the location and order of other genes and polymorphic loci in this region as well as for generating new DNA probes from specific regions.     

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.     

Cosmid linking clones localized to the long arm of human chromosome 11.

Molecular probes that contain DNA flanking CpG-rich restriction sites are extremely valuable in the construction of physical maps of chromosomes and in the identification of genes associated with hypomethylated HTF (HpaII tiny fragment) islands. We describe a new approach to the isolation and characterization of linking clones in arrayed chromosome-specific cosmid libraries through the large-scale semiautomated restriction mapping of cosmid clones. We utilized a cosmid library representing human chromosome 11q12-11qter and carried out automated restriction enzyme analysis, followed by regional localization to chromosome 11q using high-resolution in situ suppression hybridization. Using this approach, 165 cosmid linking clones containing one or more NotI, BssHII, SfiI, or SacII sites were identified among 960 chromosome-specific cosmids. Furthermore, this analysis allowed clones containing a single site to be distinguished from those containing clusters of two or more rare sites. This analysis demonstrated that more than 75% of cosmids containing a rare restriction site also contained a second rare restriction site, suggesting a high degree of CpG-rich restriction site clustering. Thirty chromosome 11q-specific cosmids containing rare CpG-rich restriction sites were regionally localized by high-resolution fluorescence in situ suppression hybridization, demonstrating that all of the CpG-rich sites detected by this method were located in bands 11q13 and 11q23. In addition, the distribution of (CA)n repetitive sequences was determined by hybridization of the arrayed cosmid library with oligonucleotide probes, confirming a random distribution of microsatellites among CpG-rich cosmid clones. This set of reagent cosmid clones will be useful for physical linking of large restriction fragments detected by pulsed-field gel electrophoresis and will provide a new and highly efficient approach to the construction of a physical map of human chromosome 11q.     

A genetic linkage map of chromosome 17

We have developed a genetic linkage map of 19 markers (including nine genes) on human chromosome 17, providing 13 reference points along virtually the entire length of this chromosome. The map covers an estimated 149 cM in length (sex-averaged), with a total length of 214 cM in females and 95 cM in males. This sex difference appears to be significant along virtually the entire length of the map. This map will be useful both for providing reference points for fine structure genetic and physical mapping and for genetic linkage studies of diseases, including von Recklinghausen neurofibromatosis and Charcot-Marie-Tooth disease.     

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.     

Tomato chromosome 6: a high resolution map of the long arm and construction of a composite integrated marker-order map

Integration of molecular and classical genetic maps is an essential requirement for marker-assisted breeding, quantitative trait locus mapping and map-based cloning. With respects to tomato, such maps are only available for the top part of chromosome 1, for chromosome 3 and for the short arm and the centromere proximal part of the long arm of chromosome 6. Employing an L. esculentum line carrying an L. hirsutum introgression we constructed an integrated linkage map for the telomere proximal part of the long arm of tomato chromosome 6, thereby completing the integrated map published previously. With an average map distance of only 0.6 cM the map provides detailed information on the relative position of molecular markers and several traits of economical importance, such as the fruit color marker B. Furthermore, two additional crosses using lines containing L. pennellii introgressions were performed to address the question as to how the recombination frequency in a marked interval on the long arm of chromosome 6 is affected by introgressed segments from different origins. It is concluded that recombination is not merely affected by the local level of homology but also by surrounding sequences. Combination of all the linkage data generated in various crosses described in this and other studies enabled the construction of the first integrated map of an entire tomato chromosome. This map carries 42 loci and shows the position of 15 classical genes relative to 59 molecular markers.     

Fragile site long arm chromosome 16

Summary A fragile site at the long arms (q21) of chromosome 16 was found in two persons, each of whom became the parent of a child with a de novo structural chromosome abnormality—a balanced autosomal translocation and an autosomal deletion. The question of an increased risk of structural chromosome abnormalities in the offspring of persons with fragile site long arm 16 is discussed.     

A comparative map of chicken chromosome 24 and human chromosome 11

To improve the physical and comparative map of chicken chromosome 24 (GGA24; former linkage group E49C20W21) bacterial artificial chromosome (BAC) contigs were constructed around loci previously mapped on this chromosome by linkage analysis. The BAC clones were used for both sample sequencing and BAC end sequencing. Sequence tagged site (STS) markers derived from the BAC end sequences were used for chromosome walking. In total 191 BAC clones were isolated, covering almost 30% of GGA24, and 76 STS were developed (65 STS derived from BAC end sequences and 11 STS derived within genes). The partial sequences of the chicken BAC clones were compared with sequences present in the EMBL/GenBank databases, and revealed matches to 19 genes, expressed sequence tags (ESTs) and genomic clones located on human chromosome 11q22-q24 and mouse chromosome 9. Furthermore, 11 chicken orthologues of human genes located on HSA11q22-q24 were directly mapped within BAC contigs of GGA24. These results provide a better alignment of GGA24 with the corresponding regions in human and mouse and identify several intrachromosomal rearrangements between chicken and mammals.     

Reciprocal translocation between Y chromosome long arm euchromatin and the short arm of chromosome 1

A case with an apparently balanced reciprocal translocation between the long arm of the Y chromosome and the short arm of chromosome 1 t(Y;1)(q11.2;p34.3) is described. The translocation was found in a phenotypically normal male ascertained by infertility and presenting for intra-cytoplasmatic sperm injection treatment. Histological examination of testicular biopsies revealed spermatogenic failure. Chromosome painting with probes for chromosome 1 and for the euchromatic part of the Y chromsome confirmed the translocation of euchromatic Y chromosomal material onto the short arm of chromosome 1 and of a substantial part of the short arm of chromosome 1 onto the Y chromosome. Among the Y/autosome translocations, the rearrangements involving long arm euchromatin of the Y chromosome are relatively rare and mostly associated with infertility. Microdeletion screening at the azoospermia locus revealed no deletions, suggesting another mechanism causing infertility in this translocation carrier.