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.     

Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia.

Deletions of the short arm of chromosome 9 with a minimum region of overlap at band 9p22 are frequently observed in acute lymphoblastic leukemia and in gliomas. They also occur at a lower frequency in lymphomas, melanomas, lung cancers, and other solid tumors. These deletions often include the entire interferon (IFN) gene cluster, which comprises about 26 interferon-alpha (IFNA), -omega (IFNW), and-beta-1 (IFNB1) interferon genes, as well as the gene for the enzyme methylthioadenosine phosphorylase (MTAP). By comparing microscopic deletions with the genes lost at the molecular level, we have determined the order of these genes on 9p to be telomere-IFNB1-IFNA/IFNW cluster-MTAP-centromere. In a few cell lines and in primary leukemia cells, we have observed deletions that have breakpoints within the IFN gene cluster and result in partial loss of the IFN genes. These partial deletions allowed us to determine the order of some genes or groups of genes within the IFNA/IFNW gene cluster. Our current results map the shortest region of overlap of these deletions in the various tumors to the region between the centromeric end of the IFNA/IFNW gene cluster and the MTAP gene locus.     

Linkage analysis and allelic imbalance in human breast cancer kindreds using microsatellite markers from the short arm of chromosome 3

Eight Icelandic breast cancer kindreds were subjected to linkage analyses with respect to 28 microsatellite loci dispersed along the short arm of chromosome 3. Breast tumors derived from these kindreds were concurrently scored for allelic imbalance with ten of the markers. Linkage to most markers could be excluded on the basis of negative LOD scores and haplotype analyses, although some moderately positive LOD scores resulted. A high frequency of imbalance in the familial tumors was seen with two of the markers in comparison with results obtained from sporadic material. The highest frequency (68%) of imbalance was detected with the marker D3S1217, which is located on 3p14.2-p14.1. Imbalance at the D3S1211 locus, which is more telomeric (3p24.2-p22), was not significantly elevated in the familial tumors. We suggest that the genetic defect responsible for breast cancer susceptibility in these families either promotes instability in the 3p14.2-p14.1 region or enhances the selective advantage of such changes.     

Genetic evidence of mutator-induced deletions in the short arm of chromosome 9 of maize

Evidence is presented that at least 12 of the Mu-induced yg2 mutants found in an extensive mutation analysis of this locus are the result of deletions in the region of the yg2 locus on the short arm of chromosome 9. Twelve of these putative deletions were characterized genetically, and in every instance, they were confirmed to be deletions involving chromosomal segments that include the yg2 and wd loci as well as additional portions of the short arm of chromosome 9.     

A study of females with deletions of the short arm of the X chromosome

We have undertaken a clinical and molecular study of 25 females with deletions of the short arm of the X chromosome. We have determined the deletion breakpoints, the parental origin and the activation status of the deleted X chromosomes. Genotype–phenotype correlations suggest that the presence of a single copy of the DFFRX gene, previously postulated as a gene involved in the ovarian failure seen in Turner syndrome, may be compatible with normal ovarian function, and that there may be a gene for Turner-like features located in distal Xp22.3. Received: 26 November 1997 / Accepted: 18 December 1997     

Frequent deletions of the human X chromosome distal short arm result from recombination between low copy repetitive elements

Substantial DNA deletions appear to be the molecular basis of several human genetic disorders but rarely account for the majority of observed mutations at any given locus. Exceptions in which deletions do account for the majority of observed abnormalities include the alpha-thalassemias, Duchenne muscular dystrophy, and steroid sulfatase deficiency. Variable deletion breakpoints have been recognized at the alpha-globin and dystrophin loci, but no information is available regarding STS deletions. We have found that these STS alterations usually involve breakpoints within highly similar sequence elements situated approximately 1.9 megabases apart on the X chromosome. It is surprising that these very large deletions produce such mild clinical abnormalities. These results may provide insight into the molecular mechanism of a number of human genetic defects.     

Partial deletion of the short arm of chromosome 8]

Partial monosomy 8p is reported in a patient with mild mental deficiency and a facial dysmorphia (a triangular mandible and a peculiarly shaped nose with straight parallel margins).     

Interstitial deletion of the short arm of chromosome 3

Summary A de novo interstitial deletion of the short arm of chromosome 3 was prenatally diagnosed in a male fetus, karyotype 46,XY,del(3)(pterp14.2::p11qter). The fetus had craniofacial dysmorphisms, a single transverse palmar crease, ulnar deviation in the wrists, cardiovascular anomalies, a slight ureteric dilatation and a mobile caecum. Our observations are compared with five other cases with interstitial deletion of the short arm of chromosome 3 to delineate further the proximal 3p deletion syndrome. The gene for beta-galactosidase-1 (GLB-1) has previously been assigned to chromosome 3(p21q21). The absence of a gene dosis effect for GLB-1 in this study indicates exclusion of GLB-1 from 3(p11p14.2).     

Regional localization of DNA probes on the short arm of chromosome 11 using aniridia-Wilms' tumor-associated deletions

Summary We are interested in the precise localization of various DNA probes on the short arm of chromosome 11 for our research on the aniridia-Wilms' tumor association (AWTA), assigned to region 11p13 (Knudson and Strong 1972; Riccardi et al. 1978). For this purpose we have screened lymphocyte DNA and material derived from somatic cell hybrids from individuals with constitutional 11p deletions with a range of available probes: D11S12; calcitonin/CGRP (CALC1/CALC2); insulin (INS); Harvey ras 1 (HRAS 1); beta-globin gene cluster (HBBC); human insulin-like growth factor 2 (IGF-2); parathyroid hormone (PTH); human pepsinogen A (PGA). Using this material, it has been possible to map all probes used, except insulin, outside the region 11p111-p15.1, resulting in an SRO (same regional overlap) of 11p15.1-p15.5 for most probes. We found an SRO for PGA of 11p111-q12 and an SRO for CALC2 of 11p15.1-p15.5 or 11p111-q12. We have localised the insulin gene to band 11p15.1.     

The most frequently lost allelic site in human renal cell carcinoma (D3F15S2) on the short arm of chromosome 3 has homologous sequences on rat chromosome 8

It has previously been shown that human chromosome 3 has banding homology to rat chromosome 8. We have previously isolated a cDNA from the D3F15S2 region and designated the gene as RIK. In the present study, we localized the homolog of this gene to rat chromosome 8.     

Silver staining studies on the short arm variant of human chromosome 17

Summary The absence of silver grain precipitation on human chromosome 17, consistently observed in four patients displaying the 17p variant, supports the hypothesis that the 17p variant is a structural heteromorphism rather than translocated satellite material.     

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.     

Familial paracentric inversion of the short arm of chromosome 3.

A paracentric inversion of the short arm of chromosome number 3 is reported in three generations of a family. The index patient presented with slight psychomotor retardation. The literature on this subject is briefly reviewed.     

The human calcitonin gene is located on the short arm of chromosome 11

By molecular hybridization of human calcitonin cDNA probes to DNA from human-rodent hybrid cells containing identified human chromosomes, we have mapped the human calcitonin gene to the short arm of chromosome 11. This location has been confirmed by in situ hybridization, which further localized the calcitonin gene to region 11p13-15. The significance of this region regarding gene linkage and possible markers for inherited cancers is discussed.     

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.     

The N-ras oncogene assigned to the short arm of human chromosome 1

The human N-ras oncogene, isolated from the HL-60 promyelocytic leukemia cell line, is distantly related to viral oncogenes of Kirsten and Harvey sarcoma viruses. We have determined its chromosomal location by Southern blot analysis of DNAs from 37 human x rodent hybrid cell lines derived from 8 different human donors, some of whom carried balanced rearrangements of chromosome 1. The results indicate that the N-ras oncogene (RASN) is localized on the proximal part of the short arm of human chromosome 1, in region p3200 leads to cen.     

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.     

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.     

Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting

Summary We have determined the subchromosomal location of the human insulin gene by analyzing DNA isolated from sorted human metaphase chromosomes. Metaphase chromosome suspensions were sorted into fractions according to relative Hoechst fluorescence intensity by the fluorescence activated chromosome sorter. The chromosomal DNA in each fraction was characterized by restriction endonuclease analysis. Initial sorts indicated that the insulin gene-containing fragment resided in a fraction containing chromosomes 9, 10, 11 and 12. Studies of cell lines that contained chromosome translocations permitted the assignment of the insulin gene to a derivative chromosome that contains portions of the short arm of chromosome 11. Simultaneous sorting of the normal homolog from this small derivative chromosome separated the two different sized insulin gene-containing restriction fragments in this individual. These data indicate that the two restriction fragments represent insulin gene polymorphism and not duplicate gene loci.