L.L. Haley

Interleukin 2 (IL2) is assigned to human chromosome 4

The human gene for interleukin 2 (IL2)was assigned to chromosome 4 using human-mouse somatic cell hybrids and Southern filter hybridization of cell hybrid DNA. To identify IL2,a recombinant DNA probe (pIL2-50A) was used which contained a human interleukin 2 cDNA insert which hybridized to a 3.5-kb fragment in human DNA when cleaved with the restriction enzyme EcoRL.

Human ?-glucuronidase: Assignment of the structural gene to chromosome 7 using somatic cell hybrids

Abstractβ-Glucuronidase (GUS) has become an important enzyme model for the genetic study of molecular disease, enzyme realization, and therapy, and for the biogenesis and function of the lysosome and lysosomal enzymes. The genetics of human β-glucuronidase was investigated utilizing 188 primary man-mouse and man-Chinese hamster somatic cell hybrids segregating human chromosomes. Cell hybrids were derived from 16 different fusion experiments involving cells from ten different and unrelated individuals and six different rodent cell lines. The genetic relationship of GUS to 28 enzyme markers representing 19 linkage groups was determined, and chromosome studies on selected cell hybrids were performed. The evidence indicates that the β-glucuronidase gene is assigned to chromosome 7 in man. Comparative linkage data in man and mouse indicate that the structural gene GUS is located in a region on chromosome 7 that has remained conserved during evolution. Involvement of other chromosomes whose genes may be important in the final expression of GUS was not observed. A tetrameric structure of human β-glucuronidase was demonstrated by the formation of three heteropolymers migrating between the human and mouse molecular forms in chromosome 7 positive cell hybrids. Linkage of GUS to other lysosomal enzyme genes was investigated. β-Hexosaminidase HEXB) was assigned to chromosome 5; acid phosphatase2(ACP2) and esterase A4(ES-A4) were assigned to chromosome 11; HEXA was not linked to GUS; and α-galactosidase (α-GAL) was localized on the X chromosome. These assignments are consistent with previous reports. Evidence was not obtained for a cluster of lysosomal enzyme structural genes. In demonstrating that GUS was not assigned to chromosome 9 utilizing an X/9 translocation segregating in cell hybrids, the gene coding for human adenylate kinase1 was confirmed to be located on chromosome 9.

Assignment of the human collagen α1(XIII) chain gene (COL13A1) to the q22 region of chromosome 10

Abstract Type XIII collagen is a recently described collagen that resembles in structure the short-chain collagens of types IX, X, and XII. Unlike any other collagen, the type XIII is found in several different forms generated through alternative splicing. A 2.0-kb genomic fragment from the human α1(XIII) collagen gene was isolated and shown by DNA sequencing to contain exon 12 as counted from the 3′ end. This fragment was used as a probe to localize the gene. The gene (COL13A1) was assigned to chromosome 10 by hybridization of the probe to DNA isolated from a panel of human-mouse somatic cell hybrids containing different human chromosomes. Furthermore, the gene was mapped to the q22 region by in situ hybridization to metaphase chromosomes.

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.

Isolation of a human laminin B2 (LAMB2) cDNA clone and assignment of the gene to chromosome region 1q25→q31

Laminin B2 is one of the three polypeptide chains of laminin, a large, complex glycoprotein synthesized by a variety of cells and specifically deposited in basement membranes. A cloned cDNA that encodes the human laminin B2 chain was isolated and characterized. The human laminin B2 gene (LAMB2) was assigned to region 1q25----q31 by (1) hybridization of the probe to DNA from a panel of human x mouse somatic cell hybrids containing different human chromosomes and (2) in situ hybridization to isolated metaphase chromosomes.

Assignment of peptidase S (PEPS) to chromosome 4 in man using somatic cell hybrids

SummaryA starch gel electrophoretic procedure is described that resolves peptidase S (PEPS) as well as the peptidases A, B, and C in man-rodent, rodent-rodent, and primate-rodent interspecific somatic cell hybrids. The interspecific PEPS cell hybrid phenotype can be resolved into a pattern which suggests that PEPS is composed of five or six identical subunits.Results are presented supporting assignment of the PEPS locus to chromosome 4 in man using man-mouse and man-Chinese hamster somatic cell hybrids. Human genes coding for peptidases A, B, C, and D were assigned to chromosome 18, 12, 1, and 19, respectively, confirming previous assignments. These somatic cell genetic data demonstrate the independent genetic control of the several human peptidases.

Assignment of the human phosphoserine phosphatase gene (PSP) to the pter→q22 region of chromosome 7

Phosphoserine phosphatase (PSP) catalyzes the hydrolysis of phosphoserine to serine. PSP expression has been examined in human-mouse somatic cell hybrids retaining different combination of human chromosomes. Human PSP is expressed only when the pter leads to q22 segment of the human 7 and its enzyme marker beta-glucuronidase (GUSB) are retained in cell hybrids. The structural gene, PSP, is therefore assigned to this region of the human 7.

Gene sequences coding for S-adenosylmethionine decarboxylase are present on human chromosome 6 and the X and are not amplified in colon neoplasia

Sequences for human S-adenosylmethionine decarboxylase, an enzyme involved in polyamine biosynthesis, which is elevated in tumors, have been localized on chromosome 6 and the X.

Human-mouse cell hybrids, a suggestion of structural mutation for dipeptidase-2 deficiency in mouse cells.

The dipeptidase-2 enzyme is inactive in certain cultured cell lines from the mouse. In somatic cell hybrids between such deficient cells and diploid human fibroblasts, the mouse deficiency was complemented when the homologous human peptidase-A was retained. The results suggested that the murine peptidase deficiency was the result of a structural mutation, rather than a regulatory one.