Assignment of human gene encoding testis-specific lactate dehydrogenase C to chromosome 11, region p14.3-p15.5

The human gene coding for lactate dehydrogenase C (LDHC), a testis-specific isozyme, has been assigned to a refined region of chromosome 11, p14.3–p15.5, in which the lactate dehydrogenase A gene LDHA also resides, by using somatic cell hybrids and in situ chromosome hybridization. This assignment clearly indicates the close physical proximity of the LDHC and LDHA genes and supports the evolutionary closeness of these two isozymes.     

Regional localization of the intestinal mucin gene MUC3 to chromosome 7q22

The gene MUC3 which codes for a mucin expressed in intestine (Gum et al. 1990) has previously been mapped, using somatic cell hybrids, to chromosome 7. We describe here the regional localization of MUC3 to chromosome 7q22 by in situ hybridization. Preliminary linkage analysis using CEPH (Centre d'Étude du Polymorphisme Humain) families supports this assignment and places MUC3 in the same linkage group as COL1A2 and CFTR.     

Comparative mapping of 9 human chromosome 22q loci in the laboratory mouse

We present a comparative map of genes on human chromosome 22qand homologous loci In the mouse genome. Gene order in humanswas established using a panel of somatic cell hybrids. Geneticmaps spanning homologous segments on three mouse chromosomeswere generated using an Interspecific backcross. The conservedlinkage between human chromosome 22 and mouse chromosome 16Includes two closely linked loci, Comt and Igl-1. The secondconserved linkage involves human chromosome 22 and mouse chromosome11 and contains two genetically and physically linked loci,Lif and Nfh. Finally, conserved synteny involving mouse chromosome15 and human chromosome 22 spans 30 cM and contains five loci(Acr, Bzrp, Dia-1, II2rb and Pdgfb). Loci within this conservedsynteny have been sublocalized to different portions of humanchromosome 22. The order of genes on mouse chromosome 15 andhuman chromosome 22 provides further evidence for chromosomalrearrangements within the conserved synteny that have occurredsince the divergence of lineages leading to mice and humans.     

Regional mapping of the gene for familial Mediterranean fever on human chromosome 16p13

Familial Mediterranean fever (FMF) is an autosomal recessively inherited inflammatory disorder characterized by recurrent short spisodes of fever, peritonitis, arthritis, and pleuritis. Recently, linkage was demonstrated between FMF and the VNTR probes 3′HVR and 5′HVR of the α-globin complex at 16p13.3 ( = 0.06?0.10, Lod_max = 9.76?14.47) and the insertion/deletion polymorphism detected by the probe CMM65 of D16S84 ( = 0.04, Lod_max = 9.17). WE have now mapped the FMF gene between the two flanking markers D16S283/D16S291 ( = 0.038) and D16S80 ( = 0.159). The proximity of the microsatellite markers in D16S283 and D16S291 to the FMF gene allows preclinical diagnosis in most pedigrees with affected individuals. © 1993 Wiley-Liss, Inc.     

Regional mapping of human DNA excision repair gene ERCC4 to chromosome 16pl3.13-pl3.2

Mitomycin C (MMC)-resistant interspecific somatic cell hybridsmade between human cells and the MMC-sensitive, Chinese hamsterovary (CHO) excision repair-deficient UV41 cells generally containedhuman chromosome 16, while other human chromosomes were randomlypresent. MMC-sensitive and -resistant subclones were isolatedfrom resistant clones and resistance generally segregated concordantlywith human chromosome 16 markers. UV radiation survival analysisof subclones indicated that MMC and UV resistance were correlated.Therefore the complementing gene, Excision Repair Cross Complementing4 (ERCC4) was assigned to human chromosome 16. Complementationof UV41 by human cells derived from patients with xerodermapigmentosum groups A, C, D and F excluded ERCC4 from involvementin those disease syndromes. Resistant hybrids containing onlyportions of chromosome 16 were identified by the lack of concordanceof multiple chromosome 16 markers. When such hybrids were usedas a source of probe for fluorescent in situ hybridization ontonormal human metaphases, the only region of chromosome 16 identifiedas being consistently present was 16pl3.1–pl3.3. Geneticmarker analysis of informative hybrids with mapped probes refinedthe position of ERCC4 to 16pl3.13–pl3.2 and allowed thefollowing order of markers within the region to be established:pter–(PRM1 D16S215)–D16S213–D16S53 –(D16S214,ERCC4)–D16S3–D16S96–cen ⁴To whom correspondence should be addressed     

Localization of a novel zinc finger gene to human chromosome 7q22 region by fluorescencein situ hybridization

As part of an endeavour to identify and characterize zinc finger genes of the cardiovascular system, a novel zinc finger gene, HHZ105, was isolated from a human fetal heart cDNA library. This gene was mapped by fluorescencein situ hybridization to human chromosome 7q22, a region associated with a number of genetic disorders and developmental deficiencies.     

Long-range mapping of the 11q23 region involved in chromosome aberrations in human tumors by pulsed-field gel electrophoresis with a yeast artificial chromosome

We have previously demonstrated that the RCK gene involved in t(11;14)(q23;q32) and the more centromeric MLL/ALL1 gene involved in t(4;11)(q21;q23) and t(11;19)(q23;p13) are localized on different adjacent Notl fragments by using pulsed-field gel electrophoresis (PFGE) analysis with the yeast artificial chromosome (YAC) clone yB22B2. The PFGE analysis using the YACs of YTY17 containing the prophobilinogen deaminase (PBGD), CBL2 and THY1 genes and yB22B2 allowed the following ordering of genes and breakpoints from CD3 to THY1 on 11q23: cent-CD3-ALL/MLL1-RCK-PBGD-CBL2-THY1, and the establishment of a long-range restriction map covering these genes. In addition, we showed that the FLI1 region involved in the t(11;22)(q24;q12) in Ewing's sarcoma was more telomeric region than the THY1 gene by analyzing somatic cell hybrids carrying the 11q- and/or 14q+ chromosome of the t(11;14)(q23;q32) translocation, and by PFGE analysis of the YAC clone YTY17. © 1993 Wiley-Liss, Inc.     

Regional localization of the sperm-specific lactate dehydrogenase, LDHC, gene on human chromosome 11

A cDNA clone complementary to the mRNA encoding the sperm-specific lactate dehydrogenase, LDHC, has been used to map the LDHC locus to the short arm of human chromosome 11. In situ hybridization data and analysis of mouse/human somatic cell hybrids carrying deletions of human chromosome 11 suggest that the gene is localized at p15.3-p15.5 close to the LDHA gene.     

Regional fine mapping of the multiple-aberration region involved in uterine leiomyoma,lipoma, and pleomorphic adenoma of the salivary gland to 12q15

Cytogenetic aberrations involving 12q13-15 are frequently observed in a variety of benign solid tumors. Using a chromosome walking approach combined with fluorescence in situ hybridization analysis, we were able to show that the chromosome 12 breakpoints involved in uterine leiomyoma, pleomorphic adenoma of the salivary gland, and lipoma cluster to the same chromosomal region, which we therefore designated MAR (multiple-aberration region). By comparing the G-banding pattern of prometaphase chromosomes of amniotic fluid cells and lymphocytes to the position of hybridization signals obtained with a cosmid pool encompassing this breakpoint hot spot region, MAR was assigned to 12q15. We conclude that, despite the cytogenetic breakpoint assignment to the three bands 12q13-15 in individual uterine leiomyomas, lipomas, and pleomorphic adenomas of the salivary glands in the past, most likely 12q15 is the only 12q breakpoint site in these three distinct solid tumor types.     

Regional localization of the lactase-phlorizin hydrolase gene, LCT, to chromosome 2q21

The gene LCT which codes for the intestinal disaccharidase lactase-phlorizin hydrolase has previously been mapped, using somatic cell hybrids and linkage analysis, using the CEPH families, to chromosome 2. We describe here the regional localization of LCT to chromosome 2q21 by polymerase chain reaction (PCR) analysis of somatic cell hybrids and in situ hybridization. LCT is closely linked to D2844, with a lod score of 30.6 at θ= 0.10.     

Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13- p16

Abnormal hepatic copper accumulation is recognized as an inherited disorder in man, mouse, rat and dog. The major cause of hepatic copper accumulation in man is a dysfunctional ATP7B gene, causing Wilson disease (WD). Mutations in the ATP7B genes have also been demonstrated in mouse and rat. The ATP7B gene has been excluded in the much rarer human copper overload disease non-Indian childhood cirrhosis, indicating genetic heterogeneity. By investigating the common autosomal recessive copper toxicosis (CT) in Bedlington terriers, we have identified a new locus involved in progressive liver disease. We examined whether the WD gene ATP7B was also causative for CT by investigating the chromosomal co-localization of ATP7B and C04107, using fluorescence in situ hybridization (FISH). C04107 is an anonymous microsatellite marker closely linked to CT. However, BAC clones containing ATP7B and C04107 mapped to the canine chromosome regions CFA22q11 and CFA10q26, respectively, demonstrating that WD cannot be homologous to CT. The copper transport genes CTR1 and CTR2 were also excluded as candidate genes for CT since they both mapped to canine chromosome region CFA11q22. 2-22.5. A transcribed sequence identified from the C04107-containing BAC was found to be homologous to a gene expressed from human chromosome 2p13-p16, a region devoid of any positional candidate genes.      

Human gene coding for granulocyte-colony stimulating factor is assigned to the q21-q22 region of chromosome 17

Granulocyte-colony stimulating factor (G-CSF) is a member of colony stimulating factors which regulate the proliferation and differentiation of hematopoietic progenitor cells. A full-length cDNA clone coding human G-CSF was used as a hybridization probe to detect homologous sequence in human-mouse somatic cell hybrids, flow-sorted human chromosomes, and in situ human metaphase chromosomes. The results indicate that the gene encoding human G-CSF is on the q21–q22 region of chromosome 17, which is involved in translocation of t(15;17) (q23;21) in human acutepromyelocytic leukemia.     

Genetic linkage of the human gene for phenylethanolamine N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, to DNA markers on chromosome 17q21-q22.

We have determined the genetic location of the human gene encoding phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine pathway catalyzing the synthesis of epinephrine (adrenaline) from norepinephrine. This gene is linked to DNA markers on the long arm of chromosome 17, q21-q22, most closely to the DNA markers MFD15 (D17S250) (Zmax = 15.0, theta = 0.065) and fLB17.1 (Zmax = 14.6, theta = 0.045). Multipoint linkage analysis placed the PNMT locus in the interval fLB17.1-CMM86 (D17S74), at 4 centiMorgans (cM) distal to fLB17.1, and at 17 cM proximal to CMM86. Mapping of the PNMT gene will provide the basis for genetic linkage studies in families with disease which might pathogenetically involve this enzyme. The human chromosomal region 17q21-22 identified here to harbour the PNMT gene may be syntenic to the chromosomal region in the stroke-prone spontaneously hypertensive rat (SHR-SP) recently linked to blood-pressure regulation. As an increase of PNMT activity has been associated with the development of hypertension in SHR-SP, it will be of interest to perform comparative mapping of the PNMT gene.     

The assignment of the human gene coding for complement C5 to chromosome 9q22-9q33.

The presence or absence of the human gene for the fifth component of complement (C5) was analysed in 19 human-rodent hybrid cell lines by hybridization to a radiolabelled probe derived from a human C5 cDNA clone. The segregation of C5 in these hybrids suggested that the gene is localized on chromosome 9, in the region 9q21-9qter. In situ hybridization refined the assignment of C5 to chromosome 9q22-33.     

Mapping of an autosomal dominant gene for Dupuytren's contracture to chromosome 16q in a Swedish family

Mapping of an autosomal dominant gene for Dupuytren's contracture to chromosome 16q in a Swedish family.Dupuytren's contracture (DC) (OMIM 126900) is the most common connective tissue disease of mankind and has both heritable and sporadic forms. The inherited form is most frequently observed among the xanthochroi peoples of Northern Europe where its most common manifestations are thickening of the palmar fascia and contracture of the fingers. We ascertained a five-generation Swedish family in which DC is inherited in an autosomal dominant manner with high, but incomplete, penetrance by the end of the fifth decade. Blood was collected from all affected and informative unaffected family members for the performance of a genome-wide scan at a resolution of approximately 8 cM for all autosomes. Linkage was established to a single 6 cM region between markers D16S419 and D16S3032 on chromosome 16. A maximal two-point logarithm of odds (LOD) score of 3.18 was achieved at microsatellite marker D16S415 with four other markers in the region producing LODs of >1.5.     

Assignment of the human gene encoding eukaryotic initiation factor 4E (EIF4E) to the region q21-25 on chromosome 4

We recently cloned genomic sequences containing the promoter region for the messenger RNA cap binding protein (eIF4E). As the rate-limiting step in translation, eukaryotic initiation factor 4E is important in cellular growth control. Using oligonucleotide primers specific for the promoter region in polymerase chain reactions (PCR), we amplified the human gene in a chromosome 4-specific human/rodent somatic cell panel. This panel mapped single copy genomic sequences for eIF4E in the region 4q21 to 4q25.     

Assignment of the gene for cytoplasmic glutamic-oxaloacetic transaminase to the region q24-qter of human chromosome 10

Somatic cell hybrids between thymidine kinase-deficient mouse cells and human fibroblasts carrying a translocation of the distal third of the long arm of chromosome 10 to chromosome 17 were studied for the expression of cytoplasmic glutamic-oxaloacetic transaminase. A positive correlation between the expression of human cytoplasmic glutamic-oxaloacetic transaminase and the presence of the distal third of the long arm of chromosome 10 was established.     

The human complement C8G gene, a member of the lipocalin gene family: polymorphisms and mapping to chromosome 9q34.3

Complement component C8 is a plasma glycoprotein consisting of three nonidentical polypeptide chains (α, β, γ) which are encoded by three separate genes (C8A, C8B, C8G). The γ chain whose functional role remains undefined is not related to any other complement protein but is a member of the lipocalins, a family of proteins that bind small hydrophobic ligands. The present report describes the first known polymorphisms for the human C8G gene, namely one polymorphic site in exon 1 (207T/G) and two polymorphic sites in intron 1 (213 + 37G → A; 213 + 65del3). Specific typing can be performed using simple polymerase chain reaction-based assays. C8G genotyping in eight CEPH reference families demonstrated that C8G is closely linked to a series of marker loci located in the most telomeric region of chromosome 9q. Multipoint analysis placed C8G with 1000:1 support distal to D9S207. C8G is thus located at 9q34.3. Remarkably, this chromosomal region contains at least four other lipocalin genes.     

Defining the region(s) of deletion at 6q16-q22 in human prostate cancer

Deletion of the long arm of chromosome 6 (6q) frequently occurs in many neoplasms, including carcinomas of the prostate and breast and melanoma, suggesting the location of a tumor-suppressor gene or genes at 6q. At present, however, the region of deletion has not been well defined, and the target gene of deletion remains to be identified. In this study, we analyzed 44 primary prostate cancers with 16 polymorphic markers for loss of heterozygosity (LOH) by using PCR-based techniques. We also examined 23 cell lines/xenografts of prostate cancer with 38 markers for LOH by the method of homozygosity mapping of deletion. LOH at 6q16 - q22 was detected in 21 of 44 (48%) primary tumors and in 12 of 23 (52%) cell lines/xenografts. Two regions of LOH were defined. One was 7.5 cM at 6q16 - q21 between markers D6S1716 and D6S1580, and the other was 4.3 cM at 6q22 between D6S261 and D6S1702. Whereas no correlation was found between LOH at 6q16-q22 and patient age at diagnosis or Gleason score, tumors at higher stage appear to have more frequent LOH. These findings suggest that deletion of 6q16 - q22 is a frequent event in prostate cancer, and that the deletion originates from two distinct regions. These results should be useful in identifying the target gene(s) of deletion at 6q.