The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2

The gene for the human mineralocorticoid receptor (MLR) was previously localized to chromosome 4. Here, we have localized this gene to 4q31.2 by in situ hybridization. This precise mapping of MLR will assist in the linkage analysis and genetic characterization of pseudohypoaldosteronism, an autosomal recessive disorder which likely results from a defect in the MLR gene.     

Molecular organization of the human CD3 gene family on chromosome 11q23

The genes encoding three invariant components of the human T-cell antigen receptor, the CD3 , , and chains, are located on human chromosome 11 at band q23. We isolated cosmid clones containing the human CD3 and chain genes in vectors designed for rapid and efficient chromosome walking. The human CD3 gene was located in the region immediately downstream of the CD3 and genes using synthetic oligonucleotide probes and the localization of this gene confirmed by DNA sequencing. Detailed restriction mapping of the CD3 locus demonstrated that all three CD3 subunits are encoded within 60 kb of DNA with the CD3 gene located 26 kb downstream of the CD3 and genes. Analysis of genomic DNA on pulsed field gels using probes isolated from these cosmid clones defined a physical map of 750 kb spanning the CD3 locus on human chromosome 11g23. The CD3 genes thus comprise a multigene family encoding cell surface components important for transmembrane signaling on T lymphocytes. The arrangement of these genes suggest that they may share common regulatory elements for the control of gene expression during T-cell ontogeny.     

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.     

The second human calcitonin/CGRP gene is located on chromosome 11

Summary A second human calcitonin/calcitonin gene related peptide (hCT/CGRP) gene has been identified. This second hCT/CGRP gene has been shown to contain sequences highly homologous to exons 3, 5 (CGRP-encoding), and 6 of the first hCT/CGRP gene, but sequences closely related to exon 4 (CT-encoding) could not be demonstrated. Southern blot hybridization analysis of DNA from human-rodent somatic cell hybrids showed that the second hCT/CGRP gene is located in the q12-pter region of chromosome 11. The first hCT/CGRP gene has previously been assigned to the p13–p15 region of chromosome 11.     

The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23----q24) and on mouse chromosome 19

Terminal deoxynucleotidyltransferase (TdT) is a DNA polymerase expressed in immature lymphocytes of the thymus and bone marrow, as well as certain leukemic cells. Chromosomal assignment of the gene coding for human TdT was accomplished by in situ hybridization of a 3H-labeled cDNA probe to human chromosome preparations and by Southern blot analysis of somatic cell hybrid DNAs. The human TdT gene was mapped to the region q23----q24 of chromosome 10. Breaks at this site have been reported in different translocations in human leukemias. The mouse TdT gene was assigned to chromosome 19 by Southern blot analysis of mouse X Chinese hamster somatic cell hybrids. This result adds a fourth locus to the conserved syntenic group on mouse chromosome 19 and human chromosome 10.     

The gene that encodes the human CD20 (B1) differentiation antigen is located on chromosome 11 near the t(11;14)(q13;q32) translocation site

The human CD20 gene (B1) encodes a B lymphocyte-specific, cell-surface molecule that is involved in B cell activation and differentiation. We report that the CD20 gene is located on human chromosome 11 at position q12-q13. The location of CD20 was determined by in situ hybridization and was further confirmed by Southern blot analysis of DNA from rodent/human hybrids that contained only portions of human chromosome 11. This localization places the CD20 gene near the site of the t(11;14)(q13;q32) translocation that is found in a subgroup of B cell-lineage malignancies. The site of this translocation has been previously identified by DNA cloning and termed bcl-1. The CD20 gene was found to lie on the centromeric side of bcl-1 on chromosome 11 and to be separated from bcl-1 by at least 50 kb of DNA. These results raise the possibility that alterations in the expression of the CD20 gene may result after the t(11;14) chromosomal alteration.     

The gene for human carbonic anhydrase II (CA2) is located at chromosome 8q22

The gene CA2 for the human carbonic anhydrase II isozyme is encoded in band q22 of chromosome 8. These data and supporting evidence predict that the genes for carbonic anhydrase I and III are also physically closely linked in this chromosomal region.     

The gene cluster for human U2 RNA is located on chromosome 17q21

The gene cluster for human U2 RNA has been mapped to chromosome 17q21 by in situ hybridization and hybridization analysis of DNA from mouse/human somatic cell hybrids.     

The structural gene for human coagulation factor X is located on chromosome 13q34

The gene coding for coagulation factor X was studied in a family segregating chromosomal abnormalities involving chromosomes 13 and 6. An individual monosomic for 13q34 was deficient in levels of clotting factors VII and X, while her brother, who is trisomic for 13q34, had elevated levels. DNA dosage studies with a cloned human factor X gene demonstrated that the low levels of factor X expression in the individual with the chromosome 13q34 deletion were due to the absence of one copy of the factor X structural gene. This confirms the assignment of the human gene coding for factor X to 13q34.     

The gene for human chromogranin A (CgA) is located on chromosome 14

Chromogranin A (CgA) is a protein that is present in most neuroendocrine tissues and is co-secreted with their resident hormones. We have assigned the CgA gene to human chromosome 14 by hybridization of a CgA cDNA probe cloned from a cDNA library of human medullary thyroid carcinoma cells to spots of individual human chromosomes flow-sorted onto nitrocellulose filters. Southern analysis of human genomic DNA with the same probe revealed only 1-3 restriction bands. These studies indicate that the CgA gene is probably single copy and not a member of a dispersed, multigene family. The CgA gene is not co-localized with the genes of any of the CgA-associated hormones.     

The placental ribonuclease inhibitor (RNH) gene is located on chromosome subband 11p15.5

The ribonuclease inhibitor from human placenta is a tight-binding inhibitor of alkaline and neutral ribonucleases, including the blood vessel-inducing protein, angiogenin. The location of the inhibitor gene within the human genome has now been determined. Utilizing human-rodent hybrid cell lines, it was found on chromosome 11. The localization was refined to chromosome band 11p15 by in situ hybridization of the ribonuclease inhibitor cDNA to normal metaphase chromosomes. A further refinement was obtained by in situ hybridization of the probe to metaphase chromosomes from RPMI 8402 cells, a line containing a well-characterized translocation t(11;14)(p15;q11) with a chromosome 11 breakpoint between the insulin-like growth factor 2 (IGF2) and Harvey rat sarcoma viral oncogene homolog genes. This analysis has localized the ribonuclease inhibitor gene to chromosome subband 11p15.5, distal to the IGF2 gene.     

The human neurofilament gene (NEFL) is located on the short arm of chromosome 8

We have localized the gene coding for the human neurofilament light chain (NEFL) to chromosome band 8p2.1 by Southern blotting of DNA from hybrid cell panels and in situ hybridization to metaphase chromosomes.     

The human lactase-phlorizin hydrolase gene is located on chromosome 2

The lactase-phlorizin hydrolase gene was assigned to chromosome 2 by analysis of Southern blots of DNA from a panel of human-rodent cell hybrids containing characteristic sets of human chromosomes. The hybridization probe used was a recently isolated cDNA clone of the human lactase-phlorizin hydrolase gene.     

The human apolipoprotein A-II gene is located on chromosome 1

Apolipoprotein (apo) A-II is a major constituent of high density lipoproteins (HDL). The gene for apoA-II has been localized to the p21----qter region of chromosome 1 in man by Southern blot hybridization analysis of DNA from human-mouse cell hybrids using a cloned human apoA-II cDNA probe. The regional assignment was established using two hybrids carrying a reciprocal translocation involving chromosomes 1 and 2. Comparison with previously established gene loci on chromosomes 1 suggests that apoA-II may reside in a conserved linkage group with renin and peptidase C. On the other hand, apoA-II is not linked to the apoA-I gene, which has been localized previously to chromosome 11.     

The gene for leukoencephalopathy with vanishing white matter is located on chromosome 3q27.

Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder with normal early development and, usually, childhood-onset neurological deterioration. At present, diagnosis of VWM is based on clinical examination and the results of repeat magnetic resonance imaging and magnetic resonance spectroscopy, which show that, with time, increasing amounts of the cerebral white matter vanish and are replaced by cerebrospinal fluid. We have performed a genome linkage screening of a panel of 19 families of different ethnic origins. Significant linkage to chromosome 3q27 was observed in a 7-cM interval between markers D3S3730 and D3S3592, with a maximum multipoint LOD score of 5.1 calculated from the entire data set. The results of genealogical studies have suggested that seven parents in four Dutch families with VWM may have inherited an allele for the disease from a common ancestor who lived at least eight generations ago. Analysis of these families provided further evidence for the localization of the gene for VWM to 3q27. The patients shared a haplotype spanning 5 cM between markers D3S1618 and D3S3592. In one family of a different ethnic background, the patient had, in the same region, homozygosity for 13 consecutive markers spanning at least 12 cM, suggesting consanguinity between the parents. A healthy sibling of this patient had the same homozygous haplotype, which suggests that the healthy sibling is presymptomatic for the disease.     

The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders.     

Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4

Chromosomal localization of the gene for human coagulation factor XI (F11) was determined by in situ hybridization using a genomic DNA probe which contained exons VIII, IX, and X of the gene. The results indicate that the gene is located at 4q35.