Genetic mapping of the human polymeric immunoglobulin receptor gene to chromosome region 1q31----q41

Polymeric immunoglobulin receptor (PIGR) is a transmembrane glycoprotein which is expressed by epithelial cells and is involved in the transcellular transport of polymeric immunoglobulins into secretions. We cloned the human gene for PIGR and used the clone to obtain probes to determine the chromosomal localization of PIGR. Analysis of somatic cell hybrids and in situ chromosomal hybridization localized the human PIGR gene locus to 1q31----q41.     

Adenovirus 12 uncoiler regions of human chromosome 1 in relation to the 5S rRNA genes

Two uncoiler regions, induced by adenovirus 12, have been identified on human chromosome 1 at 1q42 and 1p36. In situ hybridization with [¹²⁵I-5S]-rRNA places the 5S genes more accurately at 1q42–43 immediately distal to the uncoiled site, 1q42.     

Fine mapping of the human pentraxin gene region on chromosome 1q23

 The 1q21 to 25 region of human chromosome 1 contains genes which encode proteins with immune- and inflammation-associated functions. These include the pentraxin genes, for C-reactive protein (CRP), serum amyloid P (SAP) protein (APCS), and a CRP pseudogene (CRPP1). The region of chromosome 1 containing this cluster is syntenic with distal mouse chromosome 1. We constructed an approximately 1.4 megabase yeast artificial chromosome (YAC) contig with the pentraxin genes at its core. This four-YAC contig includes other genes with immune functions including the FCER1A gene, which encodes the α-subunit of the IgE high-affinity Fc receptor and the IFI-16 gene, an interferon-γ-induced gene. In addition, it contains the histone H3F2 and H4F2 genes and the gene for erythroid α-spectrin (SPTA1). The gene order is cen.-SPTA1-H4F2-H3F2-IFI-16-CRP-CRPP1-APCS-FCER1A- tel. The contig thus consists of a cluster of genes whose products either have immunological importance, bind DNA, or both. Received: 13 December 1995 / 6 February 1996     

Regional mapping of the FOS oncogene to rat chromosome 6q21----q23

Using a panel of rat x mouse somatic cell hybrids and in situ hybridization, we determined the chromosomal location of the rat FOS gene locus. Southern blot analysis assigned this oncogene to rat chromosome 6. In situ hybridization confirmed this finding and mapped the gene more precisely to 6q21----q2.     

Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1----q11.2.

Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is a physiologically important enzyme in the metabolism of catecholamine neurotransmitters and catechol drugs. Using primers derived from the known rat cDNA sequence for COMT, we have used the polymerase chain reaction to produce an amplified DNA fragment corresponding to the complete coding region of the rat gene. With this fragment as a probe, we have hybridized DNAs from two panels consisting of human/rodent and human/hamster somatic cell hybrids carrying various translocations and deletions to refine the chromosomal location of human COMT. Southern blot analysis indicates that the human COMT gene is localized to 22q11.1----q11.2, a region to which several anonymous DNA sequences, but until now, no structural genes, have been assigned.     

Assignment of the human dihydrofolate reductase gene to the q11----q22 region of chromosome 5.

Cells from a dihydrofolate reductase-deficient Chinese hamster ovary cell line were hybridized to human fetal skin fibroblast cells. Nineteen dihydrofolate reductase-positive hybrid clones were isolated and characterized. Cytogenetic and biochemical analyses of these clones have shown that the human dihydrofolate reductase (DHFR) gene is located on chromosome 5. Three of these hybrid cell lines contained different terminal deletions of chromosome 5. An analysis of the breakpoints of these deletions has demonstrated that the DHFR gene resides in the q11----q22 region.     

Order of genes on human chromosome 5q with respect to 5q interstitial deletions

Using (a) somatic cell hybrids retaining partial chromosome 5 and (b) clinical samples from patients with acquired deletions of the long arm of chromosome 5, combined with chromosome 5-linked DNA probes, some of which exhibited RFLPs, we have determined the order of a series of genes on chromosome 5. The order established is 5pter----MLVI-2----cen----HEXB----DHFR----Pi227- --- cp12.6----(IL5,IL4)----IL3----GMCSF---- FGFA---- (CSF1R,PDGFR)----(treC,ADRBR)----(ARH-H9,CSF1 )----qter. The suggested order and orientation for the closely linked IL3/GMCSF gene pair is cen----5' IL3 3'----5' GMCSF 3'----qter, on the basis of analysis of the GMCSF rearrangement in HL60 DNA. The map position of the GRL locus, which was consistent with both somatic cell hybrid and 5q- analyses, was telomeric to GMCSF and centromeric to CSF1R/PDGFR, near FGFA. Long-range restriction-enzyme analysis of 5q- DNAs did not detect rearrangements of 5q-linked probes except in HL60 DNA, but it did reveal putative long-range RFLPs of several loci. RFLPs for GRL, Pi227, cp12.6, IL3, and CSF1R can detect deletions in bone marrow and in leukemia cells from patients with acquired 5q deletions.     

The site of 5S RNA genes in human chromosome 1.

The major site of genes for human 5S RNA is in the long arm of chromosome 1. We find no evidence of sites in other chromosomes; if such exist, they are much smaller than the site in 1q.     

Assignment of the human calpastatin gene (CAST) to chromosome 5 at region q14----q22

The human calpastatin gene (CAST) was assigned to chromosome 5 by spot-blot hybridization analysis with flow-sorted chromosomes, and it was further sublocalized to bands 5q14----q22 using in situ hybridization to metaphase chromosomes.     

Genetic mapping of nine DNA markers in the q11----q22 region of the human X chromosome

We have ordered nine polymorphic DNA markers within detailed map of the proximal part of the human X chromosome long arm, extending from band q11 to q22, by use of both physical mapping with a panel of rodent-human somatic hybrids and multipoint linkage analysis. Analysis of 44 families (including 17 families from the Centre d'Etude du Polymorphisme Humain) provided highly significant linkage data for both order and estimation of map distances between loci. We have obtained the following order: DXS1-DXS159-DXYS1-DXYS12-DXS3-(DXS94 , DXS178)-DXYS17. The most probable location of DXYS2 is between DXS159 and DXS3, close to DXYS1 and DXYS12. The high density of markers (nine loci within 30 recombination units) and the improvement in the estimation of recombination frequencies should be very useful for multipoint mapping of disease loci in this region and for diagnostic applications.     

Fine mapping of the schizophrenia susceptibility locus on chromosome 1q22

Schizophrenia is a serious neuropsychiatric illness estimated to affect approximately 1% of the general population. As part of a genome scan for schizophrenia susceptibility loci, we have previously reported a maximum heterogeneity four-point lod score of 6.50 on chromosome 1q21-22 in a group of 22 medium-sized Canadian families, selected for study because multiple relatives were clinically diagnosed with schizophrenia or schizoaffective disorder. We have now conducted fine mapping of this locus in the same set of individuals using 15 genetic markers spanning an approximately 15-cM interval. Parametric linkage analysis with GENEHUNTER v2.1 and VITESSE v2.0 produced a maximum multipoint heterogeneity lod score of 6.50, with a Zmax-1 support interval of <3 cM, corresponding to approximately 1 Mb. Physical mapping and sequence analysis from this region confirmed the presence of an approximately 81-kb tandem duplication, containing low-affinity IgG receptor genes and heat shock protein genes. The sequences of the two copies of this duplication are approximately 97% identical, which has led to the collapse of the two copies into one in the June 2002 NCBI Build 30 of the Human Genome. This duplication may be involved in genomic instability, leading to gene deletion, and so presents an intriguing candidate locus for schizophrenia susceptibility.     

Localization of histidase to human chromosome region 12q22----q24.1 and mouse chromosome region 10C2----D1

The human gene for histidase (histidine ammonia-lyase; HAL), the enzyme deficient in histidinemia, was assigned to human chromosome 12 by Southern blot analysis of human X mouse somatic cell hybrid DNA. The gene was sublocalized to region 12q22----q24.1 by in situ hybridization, using a human histidase cDNA. The homologous locus in the mouse (Hal) was mapped to region 10C2----D1 by in situ hybridization, using a cell line from a mouse homozygous for a 1.10 Robertsonian translocation. These assignments extend the conserved syntenic region between human chromosome 12 and mouse chromosome 10 that includes the genes for phenylalanine hydroxylase, gamma interferon, peptidase, and citrate synthase. The localization of histidase to mouse chromosome 10 suggests that the histidase regulatory locus (Hsd) and the histidinemia mutation (his), which are both known to be on chromosome 10, may be alleles of the histidase structural gene locus.     

Synteny mapping in the bovine: genes from human chromosome 5.

In an effort to generate a more complete bovine syntenic map of Type I comparative anchor loci, seven homologs to genes found on HSA5 were mapped using a panel of bovine x rodent hybrid somatic cells. Five HSA5 genes, CSF2, RPS14, PDGFRB, FGFA, and CSF1R, were assigned to bovine syntenic group U22 (chromosome 7), while two others, C9 and HGMCR, mapped to U10 and U5, respectively. Previous studies had assigned the HSA5 marker SPARC to bovine syntenic group U22. The mapping of genes spanning the length of HSA5 in cattle and also in mouse permits syntenic comparisons between prototypic genomes of three mammalian orders, providing insight into the evolutionary history of this region of the ancestral mammalian genome.     

Regional localisation of the Friedreich ataxia locus to human chromosome 9q13----q21.1

We have previously assigned the Friedreich ataxia locus (FRDA) to chromosome 9; the current maximal lod score between FRDA and MCT112 (D9S15) is greater than 50 at a recombination fraction of theta = 0. The physical assignment of the locus defined by MCT112, and hence FRDA, has not been determined, although linkage analysis of MCT112 with other chromosome 9 markers inferred a location close to the centromere. We have used in situ hybridisation with MCT112, a corresponding cosmid MJ1, and DR47 (D9S5), coupled with mapping studies on hybrid cell panels, to define more precisely the location of the disease locus. The in situ location of all three probes is 9q13----q21.1, distal to the variable heterochromatin region. Physical assignment of FRDA will allow us to identify hybrid cell lines containing the mutated gene.     

Regional localization of the LCA oncogene to human chromosome region 2q14----q21

A novel human oncogene, LCA, was assigned to region 2q14----q21 by in situ molecular hybridization. The present regional mapping substantiates the previous assignment that was performed by Southern blot analyses of DNAs from flow-sorted human chromosomes and human-mouse somatic cell hybrids.