Mary G. Byers

Polymorphic Human Glucose Transporter Gene (GLUT) is on Chromosome 1p31.3→p35

The glucose transporter is a membrane glycoprotein that is involved in the uptake of glucose by most, if not all, animal cells. A cloned cDNA that encodes the human protein was used to map the gene to a specific chromosomal region and to identify a DNA polymorphism. The human gene (designated GLUT) was assigned to chromosome 1p31.3H→p35 by hybridization of the probe to DNA from a panel of human-mouse somatic cell hybrids containing different human chromosomes and by in situ hybridization to isolated metaphase chromosomes. The most likely location of GLUT is in 1p33. A common two-allele restriction-fragment-length polymorphism was identified with Xba I. Diabetes.

Chromosomal organization and localization of the human urokinase inhibitor gene: Perfect structural conservation with ovalbumin ☆

Plasminogen activator inhibitor 2 (PAI-2) plays an essential role in the regulation of localized extracellular proteolysis by its inactivation of urokinase. Using probes derived from a cDNA we isolated from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes, we have mapped, isolated, and determined the molecular organization of the gene for PAI-2 (PLANH2). In situ hybridization of the cDNA to normal metaphase chromosomes has confirmed our prior assignment of the gene for PAI-2 to chromosome 18 and further localized it to the long arm at 18q21.2-18q22. We have isolated nine independent genomic clones, two of which were found to contain the entire PAI-2 transcriptional unit of approximately 16.4 kilobase pairs (kbp). Analysis of the gene organization by restriction enzyme mapping, Southern blotting, and DNA sequencing revealed that the cDNA sequence is divided among eight exons interrupted by seven introns, the junctions of which all conform to the GT-AG consensus rule. In common with the arrangement found throughout, the serpin superfamily, of which PAI-2 is a member, the first intron is located just 5 to the initiator methionine residue, and the 3 untranslated region (UTR) is not interrupted by a splice junction. Determination of the transcription initiation site by primer extension analysis of monocytic mRNA indicated that our PAI-2 cDNA was, at most, only three nucleotides short of full length, yielding a primary PAI-2 transcript with a 66-bp first exon. A promoter TATAAAbox is located 30 bp upstream of the cap site.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Polymorphic Human Insulin-Responsive Glucose-Transporter Gene on Chromosome 17p13

Glucose uptake by heart, skeletal muscle, and adipose tissue is acutely regulated by insulin, which stimulates facilitative glucose transport, at least in part, by promoting the translocation of transporters from an intracellular pool to the plasma membrane. cDNAs encoding the major human insulin-responsive glucose transporter have been isolated and indicate that the insulin-responsive glucose transporter expressed by heart, skeletal muscle, and adipose tissue is a 509–amino acid protein having 65.3, 54.3, and 57.5% identity with the erythrocyte/HepG2, liver, and fetal muscle glucose transporters, respectively. The gene encoding the insulin-responsive glucose transporter (designated GLUT4) was mapped to the p11 → p13 region of the short arm of human chromosome 17 by analyzing its segregation in a panel of reduced human-mouse somatic cell hybrids. In situ hybridization to prometaphase chromosomes indicated that GLUT4 was in band p13. A common two-allele restriction-fragment–length polymorphism (RFLP) was identified with Kpn I, and linkage of this RFLP to other polymorphic DNA markers in this region of chromosome 17 provides a set of probes that will be useful for examining the role of this gene in the pathogenesis of diabetes mellitus.

Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene

Little is known about the primary amino acid structure of human cartilage link protein (CRTL1). We screened a human genomic library with a cDNA encoding the 3 untranslated region and the adjoining B1 domain of chicken link protein. One clone was isolated and characterized. A 3.5-kb EcoRI-KpnI fragment from this genomic clone that contains the human B1 exon was used to map the gene to chromosome 5q13----q14.1. The same fragment was used to screen a cDNA library prepared from mRNA of Caco-2, a human colon tumor cell line. Two overlapping clones were isolated and shown to encode all of CRTL1. The deduced amino acid sequence is 354 residues long. The amino acid sequence shows a striking degree of identity to the porcine (96%), rat (96%), and chicken (85%) link protein sequences. Furthermore, there is greater than 86% homology between the 3 untranslated region of the genes encoding human and porcine link proteins. These results indicate that there has been strong evolutionary pressure against changes in the coding and 3 untranslated regions of the gene encoding cartilage link protein.

Four new DNA markers are assigned to the WAGR region of 11p13: Isolation and regional assignment of 112 chromosome 11 anonymous DNA segments

One hundred eighty-three human single copy clones were isolated from the Livermore Laboratory chromosome 11 library (ID code LL11NSO1) and 112 of them were mapped to chromosome 11. Using a panel of somatic cell hybrids segregating chromosome 11 translocations and short arm deletions, 54 of the clones were assigned to one of nine segments on the short arm of chromosome 11; the remainder were assigned to the long arm. Nine of these clones map to 11p13, and four of the nine [57(D11S89), 530(D11S90), 706(D11S93), and 1104(D11S95)] are confined to the same segment within p13 that contains catalase (CAT), the beta subunit of follicle stimulating hormone (FSHB), and the Wilms tumor-aniridia (WAGR) gene complex.

The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2

The TCF8 gene encodes a zinc finger protein (Nil-2-a). Nil-2-a inhibits T-lymphocyte-specific interleukin 2 (IL2) gene expression by binding to a negative regulatory domain 100 nucleotides 5 of the IL2 transcription start site. Southern hybridization and somatic cell hybrids are used to demonstrate that the murine and human genomes contain related genes for Nil-2-a. TCF8 resides on human chromosome 10. Fluorescent in situ hybridization is employed to localize TCF8 to 10p11.2.