Biomedical subjects

S L Naylor

Publications and source records attributed to S L Naylor.

At least 109 records · Page 6Linked to original sources

PubMed1985

Structure and chromosomal localization of the human lymphotoxin gene.

We have isolated, sequenced, and determined the chromosomal localization of the gene encoding human lymphotoxin (LT). The single copy gene was isolated from a human genomic library using a 32P-labeled 116 bp synthetic DNA fragment whose sequence was based on the NH2-terminal amino acid sequence of LT. The gene spans 3 kb of DNA and is interrupted by three intervening sequences. The LT gene is located on human chromosome 6, as determined by Southern blot analysis of human-murine hybrid DNA. Putative transcriptional control regions and areas of homology with the promoters of interferon and other genes are identified.

Amino Acid Sequence↗

PubMed1985

A human c-src gene resides on the proximal long arm of chromosome 20 (cen----q131).

A molecular clone of v-src, the oncogene of Rous sarcoma virus, was used to detect and regionally localize a human c-src proto-oncogene on chromosome #20. The human c-src gene, detected as either a 28-kbp EcoRI DNA fragment or as a 15.4-kbp BglII DNA fragment, was localized to 20 cen----q131 by filter hybridization analysis of DNAs from human-rodent somatic cell hybrids. The results indicate that c-src is on the same chromosome arm as aberrations associated with myeloproliferative disease, although the possible involvement of c-src in these aberrations is unknown.

Animals↗

PubMed1985

Human group-specific component (Gc) is a member of the albumin family.

The group-specific component (Gc) is the major vitamin D-binding protein in plasma. The gene encoding Gc is linked, on human chromosome 4, to the albumin and alpha-fetoprotein genes. These two genes previously were shown to have evolved from a smaller ancestral gene by intragenic triplication. Recombinant plasmids containing human cDNA encoding Gc have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Characterization of Gc cDNA has provided the complete amino acid sequence of the protein and revealed strong sequence homology with albumin and alpha-fetoprotein. Of particular interest is a conserved pattern of disulfide bridges that form the triple-domain structures in albumin, alpha-fetoprotein, and Gc. Gc cDNA was used as a probe in Southern blot analysis of somatic-cell hybrids to confirm that the Gc locus is on chromosome 4.

Albumins↗

PubMed1985

Human apolipoprotein B-100: cloning, analysis of liver mRNA, and assignment of the gene to chromosome 2.

Human apolipoprotein B-100 (apo B-100) is the major apolipoprotein of low density lipoproteins and the principal ligand for interaction with the low density lipoprotein receptor. The human apo B-100 gene has been inserted into a lambda gt-11 expression vector, and the apo B-100 cDNA clones have been identified by screening with a monospecific apo B-100 antiserum, by screening with synthetic oligonucleotides based on the amino acid sequence of peptides isolated from apo B-100, and by immunoblot analysis of the expressed protein with a monoclonal antibody to apo B-100. The complete nucleotide and derived-amino acid sequence of a 1.7-kilobase cDNA clone of apo B-100 was determined. The 560-amino acid residues of apo B-100 contain no unique linear or repeating sequences of amino acids. The computer-predicted conformation of the apo B-100 protein contains segments of helical structure; however, a large portion of the protein is organized into beta-structure. The beta-structure may be important in lipid-apo B-100 interactions in low density lipoprotein and may contribute to the insolubility of delipidated apo B-100 in aqueous buffers. RNA blot hybridization analysis of liver mRNA utilizing a Nco I/HindIII apo B-100 cDNA probe revealed that the apo B-100 mRNA is 15-18 kilobases long, which is of sufficient size to code for a 250-387 kDa apolipoprotein, the proposed molecular size of delipidated plasma apo B-100. The gene for human apo B-100 has been localized to chromosome 2 by filter hybridization of human-mouse somatic cell hybrids utilizing a 400-base-pair Nco I/HindIII apo B-100 cDNA probe. This location is in contrast to the low density lipoprotein receptor that has been localized to chromosome 19. The cloning of human apo B-100 has provided new insights into the structure and physicochemical properties of apo B-100 and will facilitate studies on the factors modulating apo B-100 biosynthesis and the expression of the apo B-100 gene in patients with dyslipoproteinemias.

Amino Acid Sequence↗

PubMed1984

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.

Animals↗

PubMed1984

The localization of the gene for apolipoprotein C-II to chromosome 19.

Human apolipoprotein (apo) C-II, a 79 amino acid protein, functions as a cofactor for lipoprotein lipase, the enzyme which catalyzes the hydrolysis of plasma triglycerides. The chromosomal location of apoC-II has been determined by filter hybridization analysis of human-mouse hybrid cells. Southern blots of DNA from 21 human-mouse hybrid cells were hybridized with a 190 base pair nick translated probe prepared from a Hinf I digest of an apoC-II cDNA clone. Without exception, ApoC-II segregated with chromosome 19 thus establishing synteny with the apoE and LDL receptor genes known to be localized to this chromosome. The localization of the apoC-II gene to chromosome 19 will permit more detailed analysis of the genomic organization and linkages of the apolipoprotein genes.

Animals↗

PubMed1984

Human apolipoprotein A-I and C-III genes reside in the p11----q13 region of chromosome 11.

Apolipoprotein (apo) A-I is a major protein of high density lipoproteins (HDL). The gene for apoA-I has been localized to the p11 leads to q13 region of chromosome 11 by filter hybridization analysis of mouse-human hybrid cell cDNAs containing chromosome 11 translocations utilizing a cloned human apoA-I cDNA probe. The known linkage of apoA-I and apoC-III also permitted the simultaneous assignment of the apoC-III gene to the same region on chromosome 11. Comparison with previously established gene linkages on the mouse and human genome suggests that apoA-I + apoC-III may be linked to the esterase A4 and uroporphyrinogen synthase genes which are present on the long arm of human chromosome 11. The localization of the apoA-I + apoC-III genes in the p11----q13 region of chromosome 11 represents a definitive chromosomal assignment of a human apolipoprotein gene, and will now enable more detailed analysis of the geneomic organization and linkages of the apolipoprotein genes.

Animals↗

PubMed1984

Regional assignment of human protooncogene c-myb to 6q21----qter.

Using human-mouse somatic cell hybrids containing different parts of chromosome 6 and a DNA probe of the oncogene (v-myb) of avian myeloblastosis virus (AMV), we regionally mapped by Southern blot techniques the human cellular myb (c-myb) protooncogene to 6q21----qter.

Animals↗

PubMed1984

Mouse immune interferon (IFN-gamma) gene is on chromosome 10.

A cDNA clone for mouse immune interferon has been used to map the mouse interferon gamma gene (Ifg) to a specific chromosome. This clone, which contains a 638-bp insert detects an 18-kb HindIII fragment of mouse DNA. The presence of the mouse Ifg gene in cel hybrids and its chromosomal location were determined by assaying cell hybrid DNA for the presence of the 18-kb HindIII fragment by Southern filter hybridization. Under the hybridization conditions used, Chinese hamster DNA did not hybridize to the cDNA probe. The segregation of mouse chromosomes in cell hybrids indicated that Ifg is located on chromosome 10. Previously, we have mapped immune interferon to the p12.05----qter region of chromosome 12 in humans (1). This region of chromosome 12 also contains the genes for peptidase B and citrate synthase. The homologous genes in mouse are also located on chromosome 10, suggesting that these genes comprise a conserved linkage group.

Animals↗

PubMed1984

Localization of human U1 small nuclear RNA genes to band p36.3 of chromosome 1 by in situ hybridization.

U1 small nuclear RNA (U1 snRNA) is encoded by a large family of genes (30-125 copies/haploid genome) which are transcribed by RNA polymerase II. U1 snRNA is thought to function in gene splicing. Since the U1 genes were found to be greater than 20 kb apart by analyzing genomic phage clones, the chromosomal location of U1 genes in the human genome was determined using Southern filter analysis of DNA isolated from human-rodent somatic cell hybrids and by in situ hybridization. Human DNA digested with PvuII and probed with a U1-specific probe, pD2, show several major hybridizing fragments. Of these, two human PvuII fragments of 1.4 kb and 2.4 kb had unique mobilities compared to mouse fragments. In a study of 19 cell hybrids, the human-specific U1 fragments segregated with the chromosome 1 markers peptidase C and adenylate kinase 2. All other chromosomes showed greater than or equal to 19% discordancy . An additional 13 karyotyped cell hybrids, analyzed by Southern filter analysis, confirmed the assignment of this class of U1 genes to chromosome 1. Additional digests with MspI and PstI indicated that most U1 genes are located on chromosome 1. To determine if the U1 RNAs are located predominantly at one site or dispersed over chromosome 1, a tritium-labeled U1 probe was hybridized in situ to metaphase chromosomes. The majority of the grains were at band 1p36 .3, suggesting that most of the U1 genes are located in this region.

Animals↗

PubMed1984

Chromosomal assignments of human genes for serine proteases trypsin, chymotrypsin B, and elastase.

The genes for the serine proteases trypsin, chymotrypsin B, and elastase were chromosomally assigned in man using cDNA probes that have been isolated from a rat pancreatic cDNA library. DNA from human X rodent somatic cell hybrids was cleaved with BamHI or EcoRI and analyzed by Southern filter hybridization methods for the segregation of the genes for trypsin-1 (TRY1), chymotrypsin B (CTRB), and elastase-1 (ELA1). TRY1 was assigned to human chromosome 7q22----qter, CTRB to chromosome 16, and ELA1 to chromosome 12. Although the three genes are members of the same gene family, they are dispersed over different chromosomes.

Biological Evolution↗

PubMed1984

Chromosomal assignments of genes for trypsin, chymotrypsin B, and elastase in mouse.

The mouse genes for the serine proteases trypsin (Try-1), chymotrypsin B (Ctrb), and elastase (Ela-1) were chromosomally assigned using Southern blot hybridization of mouse X Chinese hamster cell hybrid DNA. cDNA probes for the three genes were hybridized to cell hybrid DNA cleaved with BamHI or HindIII and the segregation of Try-1, Ctrb, and Ela-1 was correlated with the segregation of mouse chromosomes. Try-1 is located on chromosome 6, Ctrb is on chromosome 8, and Ela-1 is on chromosome 15. The three genes fall into three syntenic groups that are conserved in the mouse and human genomes.

Animals↗

PubMed1984

Human renin gene is on chromosome 1.

DNA sequences encoding kidney renin were localized to region p21----qter of human chromosome 1 by Southern blot analysis of mouse-human somatic cell hybrids with a cloned human renin DNA probe. The renin gene may be a member of a chromosome 1 linkage group which is conserved in mouse and man. Available evidence suggests this gene is present in one copy per haploid genome. Thus those renin-like molecules detected immunologically in tissues other than the kidney (such as brain, placenta, uterus, pituitary, vasculature, and adrenal) may be derived from this single gene. Since renin messenger RNA in human kidney is about 1550 nucleotides long, reported molecular weights in excess of 45,000 for circulating renin represent posttranslational or postsecretory modifications of the polypeptide.

Chromosome Mapping↗

PubMed1984

Cellular homologs of the avian erythroblastosis virus erb-A and erb-B genes are syntenic in mouse but asyntenic in man.

Avian erythroblastosis virus, a retrovirus that causes erythroblastosis and sarcomas in infected birds, possesses two host cell-derived genes [viral (v) erb-A and erb-B]. Although v-erb-B seems to be responsible for oncogenic transformation, v-erb-A might have an enhancing effect on transformation. In chickens, the natural host for avian erythroblastosis virus, cellular (c) erb-A and erb-B genes appear to be unlinked, but their chromosomal locations in other species are unknown. To ascertain the chromosomal location of c-erb genes in man and mouse, we analyzed interspecies somatic cell and microcell hybrids by Southern filter hybridization techniques using specific v-erb-A and v-erb-B probes. We found c-erb-A sequences on human chromosome 17 (17p11----qter) and located c-erb-B on human chromosome 7 (7pter----q22). In contrast, both c-erb-A and c-erb-B reside on mouse chromosome 11.

Alpharetrovirus↗

PubMed1984

Chromosome assignments of four mouse cellular homologs of sarcoma and leukemia virus oncogenes.

Molecular probes for the oncogenes of Rous sarcoma virus (v-src), avian myeloblastosis virus (v-myb), Kirsten murine sarcoma virus (v-Ki-ras), and Harvey murine sarcoma virus (v-Ha-ras) were hybridized to the DNA from mouse-Chinese hamster somatic cell hybrids. The v-src, v-myb, v-Ki-ras, and v-Ha-ras genes each detected one or a few homologous mouse DNA fragments whose segregation was analyzed in cell hybrids. Mouse cellular homologs c-src, c-Ki-ras, c-Ha-ras, and c-myb segregated concordantly with chromosomes 2, 6, 7, and 10, respectively. Comparison with the known locations of human c-src (chromosome 20) and human c-Ha-ras1 (chromosome 11 short arm) suggests that the human and mouse homologs of these two viral oncogenes reside in conserved linkage groups. The c-Ki-ras gene on mouse chromosome 6 might reside also in a conserved linkage group, along with glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase. However, direct confirmation of this suggestion must await a demonstration that c-Ki-ras on mouse chromosome 6 is homologous to c-Ki-ras2 on the short arm of human chromosome 12.

Animals↗

PubMed1984

DNA polymorphic loci mapped to human chromosomes 3, 5, 9, 11, 17, 18, and 22.

Using the techniques of Southern filter hybridization and somatic cell genetics, seven genomic DNA fragments recognizing DNA polymorphic loci were mapped to specific chromosomes and regions of chromosomes. The seven probes, isolated from human genomic libraries, lacked repetitive sequences and were hybridized to DNA isolated from a set of human-rodent somatic cell hybrids segregating human chromosomes. These probes detected DNA sequences on human chromosomes 3, 5, 9, 11, 17, 18, and 22. These DNA polymorphic sites, which occur in 10% or greater of the population, will serve as markers for linkage studies with known polymorphic loci as well as to establish linkage with disease loci.

Animals↗

PubMed1984

Human transferrin: cDNA characterization and chromosomal localization.

Transferrin (Tf) is the major iron binding protein in vertebrate serum. It shares homologous amino acid sequences with four other proteins: lactotransferrin, ovotransferrin, melanoma antigen p97, and HuBlym-1. Antigen p97 and the Tf receptor genes have been mapped on human chromosome 3. The goal of the study described here was to initiate the characterization of the Tf gene by identifying and characterizing its cDNA and mapping its chromosomal location. Recombinant plasmids containing human cDNA encoding Tf have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Within the 2.3 kilobase pairs of Tf cDNA analyzed, there is a probable leader sequence encoded by 57 nucleotides followed by 2037 nucleotides that encode the homologous amino and carboxyl domains. During evolution, three areas of the homologous amino and carboxyl domains have been strongly conserved, possibly reflecting functional constraints associated with iron binding. Chromosomal mapping by in situ hybridization and somatic cell hybrid analysis indicate that the Tf gene is located at q21-25 on human chromosome 3, consistent with linkage of the Tf, Tf receptor, and melanoma p97 loci.

Amino Acid Sequence↗

PubMed1984

Regional localization of two human cellular Kirsten ras genes on chromosomes 6 and 12.

Human cellular Kirsten ras1 and ras2 genes were localized to chromosomes 6p23 ----q12 and 12p12 .05----pter, respectively, using human-rodent cell hybrids. Thus, the short arms of human chromosomes 11 (encoding lactate dehydrogenase-A and the proto-oncogene c-Ha- ras1 ) and 12 (encoding lactate dehydrogenase B and c-Ki- ras2 ) share at least two pairs of genes that probably evolved from common ancestral genes.

Animals↗