Showing papers on "Gene published in 1986"
TL;DR: The isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus is described, which is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas.
Abstract: The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells. There is evidence for another class of oncogenes, in which tumour-predisposing mutations are recessive to wild-type alleles. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb, assigned to the q14 band of human chromosome 13. Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours, almost half of which are osteosarcomas believed to be caused by the same mutation. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13q14, all or part of which is frequently deleted in retinoblastomas and osteosarcomas.
2,827 citations
TL;DR: Five sequences coding for proteins homologous to components of the respiratory‐chain NADH dehydrogenase from human mitochondria have been found and sequence and expression analyses indicate both prokaryotic and eukaryotic features of the chloroplast genes.
Abstract: The complete nucleotide sequence (155 844 bp) of tobacco (Nicotiana tabacum var. Bright Yellow 4) chloroplast DNA has been determined. It contains two copies of an identical 25 339 bp inverted repeat, which are separated by a 86 684 bp and a 18 482 bp single-copy region. The genes for 4 different rRNAs, 30 different tRNAs, 39 different proteins and 11 other predicted protein coding genes have been located. Among them, 15 genes contain introns. Blot hybridization revealed that all rRNA and tRNA genes and 27 protein genes so far analysed are transcribed in the chloroplast and that primary transcripts of the split genes hitherto examined are spliced. Five sequences coding for proteins homologous to components of the respiratory-chain NADH dehydrogenase from human mitochondria have been found. The 30 tRNAs predicted from their genes are sufficient to read all codons if the ;two out of three' and ;U:N wobble' mechanisms operate in the chloroplast. Two sequences which autonomously replicate in yeast have also been mapped. The sequence and expression analyses indicate both prokaryotic and eukaryotic features of the chloroplast genes.
2,184 citations
TL;DR: It was found that the gene 5 promoter is active in a tissue-specific fashion whereas this is not the case for the NOS promoter, providing the first documented instance of a gene derived from a procaryotic host the expression of which is apparently regulated by plant growth factors.
Abstract: A “plant gene vector cassette” to be used in combination with various Escherichia coli gene-cloning vectors was constructed. This cassette contains a replication and mobilization unit which allows it to be maintained and to be transferred back and forth between E. coli and Agrobacterium tumefaciens hosts provided these hosts contain plasmid RK2 replication and mobilization helper functions. The cassette also harbors a transferable DNA unit with plant selectable marker genes and cloning sites which can be combined with different bacterial replicons, thus facilitating the reisolation of transferred DNA from transformed plants in E. coli. The vector cassette contains two different promoters derived from the T-DNA-encoded genes 5 and nopaline synthase (NOS). By comparing the levels of expression of the marker enzymes linked to each of these promoter sequences, it was found that the gene 5 promoter is active in a tissue-specific fashion whereas this is not the case for the NOS promoter. This observation provides the first documented instance of a gene derived from a procaryotic host the expression of which is apparently regulated by plant growth factors.
2,064 citations
TL;DR: Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VzV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.
Abstract: Summary The entire DNA sequence of varicella-zoster virus (VZV) was determined using the M13-dideoxynucleotide technology. The genome is variable in size, but the sequence which was obtained comprises 124884 bp. Analysis of the sequence indicated that the genome contains 70 genes distributed about equally between the two DNA strands. The genes are organized compactly, but regions of overlap between protein-coding regions are not extensive. Many of the genes are arranged in 3′-coterminal families, and at least one is spliced. The discerned organization of VZV genes and that deduced for herpes simplex virus type 1 (HSV-1) from published transcript mapping data indicate that these two members of the Alphaherpesvirinae are very similar in gene layout. Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VZV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.
1,451 citations
TL;DR: The complete sequence of the chloroplast DNA from a liverwort, Marchantia polymorpha, is determined and the gene organization is deduced, including coding sequences for four kinds of ribosomal RNAs, 32 species of transfer RNAs and 55 identified open reading frames for proteins, which are separated by short A+T-rich spacers.
Abstract: Chloroplasts contain their own autonomously replicating DNA genome. The majority of proteins present in the chloroplasts are encoded by nuclear DNA, but the rest are encoded by chloroplast DNA and synthesized by the chloroplast transcription–translation machinery1–4. Although the nucleotide sequences of many chloroplast genes from various plant species have been determined, the entire gene organization of the chloroplast genome has not yet been elucidated for any species of plants. To improve our understanding of the chloroplast gene system, we have determined the complete sequence of the chloroplast DNA from a liverwort, Marchantia polymorpha, and deduced the gene organization. As reported here the liverwort chloroplast DNA contains 121,024 base pairs (bp), consisting of a set of large inverted repeats (IRA and IRB, each of 10,058 bp) separated by a small single-copy region (SSC, 19,813 bp) and a large single-copy region (LSC, 81,095 bp). We detected 128 possible genes throughout the liverwort chloroplast genome, including coding sequences for four kinds of ribosomal RNAs, 32 species of transfer RNAs and 55 identified open reading frames (ORFs) for proteins, which are separated by short A+T-rich spacers (Fig. 1). Twenty genes (8 encoding tRNAs, 12 encoding proteins) contain introns in their coding sequences. These introns can be classified as belonging to either group I or group II, as described for mitochondria5. Interestingly, seven of the identified ORFs show high homology to unidentified reading frames (URFs) found in human mitochondria6,7.
1,407 citations
TL;DR: It is determined that the bcl-2 (B-cell leukemia/lymphoma 2) gene is transcribed into three overlapping mRNAs, and the cDNA clones corresponding to the three bCl-2 transcripts contain at least two exons.
Abstract: We have determined that the bcl-2 (B-cell leukemia/lymphoma 2) gene is transcribed into three overlapping mRNAs, and we have cloned bcl-2 cDNA sequences. Sequence analysis of the bcl-2 cDNA clones and comparison of their sequences to their genomic counterparts indicate that the bcl-2 gene contains at least two exons. The three bcl-2 transcripts, which are 8.5, 5.5, and 3.5 kilobases (kb) long, overlap within the first exon, but only the 8.5-kb and 5.5-kb transcripts contain sequences of the second exon. The 8.5-kb and 5.5-kb transcripts seem to use different polyadenylylation sites. Sequence analysis of the cDNA clones corresponding to the 5.5-kb and 3.5-kb mRNAs indicates that the two bcl-2 transcripts carry two overlapping open reading frames, one of which is 717 nucleotides long and codes for a protein (bcl-2 alpha) of 239 amino acids and a molecular mass of 26 kDa, while the other codes for a protein of 205 amino acids (bcl-2 beta, molecular mass 22 kDa) that is identical to bcl-2 alpha except at the carboxyl terminus. The bcl-2 protein products in follicular lymphomas with or without bcl-2 rearrangements are identical to the normal bcl-2 products.
1,170 citations
TL;DR: Transcriptionally active nuclear extracts have been prepared from rat liver, brain, and spleen and the adenovirus-2 major late promoter directs efficient transcription by RNA polymerase II in all of these extracts, whereas the promoter of the mouse albumin gene is significantly used only in the liver extract.
1,149 citations
TL;DR: A comparison of the bovine and human MIS proteins reveals a highly conserved C-terminal domain that shows marked homology with human transforming growth factor-beta and the beta chain of porcine inhibin.
1,082 citations
TL;DR: The complete nucleotide and primary structure of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented and strong homology suggests that a highly conserved functional unit involved in membrane transport is present in the mdr polypeptide.
1,054 citations
TL;DR: There are several biological systems in which uidA-encoded beta-glucuronidase may be an attractive alternative or complement to previously described gene-fusion markers such as beta-galactosidase or chloramphenicol acetyltransferase.
Abstract: We have developed a gene-fusion system based on the Escherichia coli beta-glucuronidase gene (uidA). The uidA gene has been cloned from E. coli K-12 and its entire nucleotide sequence has been determined. beta-Glucuronidase has been purified to homogeneity and characterized. The enzyme has a subunit molecular weight of 68,200, is very stable, and is easily and sensitively assayed using commercially available substrates. We have constructed gene fusions of the E. coli lacZ promoter and coding region with the coding region of the uidA gene that show beta-glucuronidase activity under lac control. Plasmid vectors have been constructed to facilitate the transfer of the beta-glucuronidase coding region to heterologous control regions, using many different restriction endonuclease cleavage sites. There are several biological systems in which uidA-encoded beta-glucuronidase may be an attractive alternative or complement to previously described gene-fusion markers such as beta-galactosidase or chloramphenicol acetyltransferase.
1,051 citations
TL;DR: The nucleotide sequence of two highly conserved DNA fragments from the DXS164 locus and their homologous sequences from the mouse X chromosome are presented and are candidates for portions of the gene responsible for both DMD and BMD.
Abstract: Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) are human X-linked muscle-wasting disorders that have been localized to the band Xp21 by genetic linkage analysis1–9 and cytologically detectable abnormalities10–12. A cloned DNA segment, DXS164 (or pERT87), has been shown to detect deletions in the DNA of unrelated DMD and BMD males13–15. Here we present the nucleotide sequence of two highly conserved DNA fragments from the DXS164 locus and their homologous sequences from the mouse X chromosome. One of the human conserved segments hybridized to a large transcript in RNA isolated from human fetal skeletal muscle and was used to isolate cDNA clones which cover approximately 10% of this transcript. The cDNA clones map to Xp21 and hybridize with a minimum of eight small regions that span 130 kilobases (kb) of the DXS164 locus. These expressed sequences are candidates for portions of the gene responsible for both DMD and BMD.
TL;DR: It is reported here the identification of a human B-cell nuclear factor (IgNF-A) that binds to DNA sequences in the upstream regions of both the mouse heavy and κ light-chain gene promoters and also to the mouseHeavychain gene enhancer.
Abstract: Trans-acting factors that mediate B-cell specific transcription of immunoglobulin genes have been postulated based on an analysis of the expression of exogenously introduced immunoglobulin gene recombinants in lymphoid and non-lymphoid cells. Two B-cell-specific, cis-acting transcriptional regulatory elements have been identified. One element is located in the intron between the variable (V) and constant (C) regions of both heavy and κ light-chain genes and acts as a transcriptional enhancer1–6. The second element is found upstream of both heavy and κ light-chain gene promoters. This element directs lymphoid-specific transcription even in the presence of viral enhancers7–10. We have sought nuclear factors that might bind specifically to these two regulatory elements by application of a modified gel electrophoresis DNA binding assay11–13. We report here the identification of a human B-cell nuclear factor (IgNF-A) that binds to DNA sequences in the upstream regions of both the mouse heavy and κ light-chain gene promoters and also to the mouse heavy-chain gene enhancer. This sequence-specific binding is probably mediated by a highly conserved sequence motif, ATTTGCAT, present in all three transcriptional elements. Interestingly, a factor showing similar binding specificity to IgNF-A is also present in human HeLa cells.
Patent•
17 Jan 1986TL;DR: In this paper, a novel transformation vector containing novel chimeric genes allows the introduction of exogenous DNA fragments coding for polypeptide toxins produced by Bacillus thuringiensis or having substantial sequence homology to a gene coding for a polypeptic toxin as described herein and expression of the chimeric gene in plant cells.
Abstract: Novel transformation vectors containing novel chimeric genes allow the introduction of exogenous DNA fragments coding for polypeptide toxins produced by Bacillus thuringiensis or having substantial sequence homology to a gene coding for a polypeptide toxin as described herein and expression of the chimeric gene in plant cells and their pro- gency after integration into the plant cell genome. Transformed plant cells and their progeny exhibit stably inherited polypeptide toxin expression useful for protecting said plant cells and their progeny against certain insect pests and in controlling said insect pests.
TL;DR: The primary structure of PrP encoded by the gene of a healthy animal does not differ from that encoded by a cDNA from a scrapie-infected animal, suggesting that the different properties ofPrP from normal and scrapie -infected brains are due to post-translational events.
TL;DR: Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G- CSF gene in CHU -2 cells.
Abstract: Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of hormone-like glycoproteins that regulate haematopoietic cell proliferation and differentiation1,2, and G-CSF almost exclusively stimulates the colony formation of granulocytes from committed precursor cells in semi-solid agar culture2. Recently, Nomura et al.3 have established a human squamous carcinoma cell line (designated CHU-2) from a human oral cavity tumour which produces large quantities of CSF constitutively, and the CSF produced by CHU-2 cells has been purified to homogeneity from the conditioned medium. We have now determined the partial amino-acid sequence of the purified G-CSF protein, and by using oligonucleotides as probes, have isolated several clones containing G-CSF complementary DNA from the cDNA library prepared with messenger RNA from CHU-2 cells. The complete nucleotide sequences of two of these cDNAs were determined and the expression of the cDNA in monkey COS cells gave rise to a protein showing authentic G-CSF activity. Furthermore, Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G-CSF gene in CHU-2 cells.
TL;DR: The results indicated that variation throughout the viral genome is extensive and that the envelope gene in particular is most highly variable, and changes were most prevalent within the extracellular region where clustered nucleotide substitutions and deletions/insertions were evident.
TL;DR: The use of retroviral vectors to introduce exogenous DNA sequences into a stem- cell line is reported and it is shown that these modified cells contribute extensively to the somatic and germ-cell lineages in chimaeric mice.
Abstract: Embryonic stem cells isolated directly from mouse embryos1 can be cultured for long periods in vitro and subsequently repopulate the germ line in chimaeric mice2,3. During the culture period these embryonic cells are accessible for experimental genetic manipulation4–6. Here we report the use of retroviral vectors to introduce exogenous DNA sequences into a stem-cell line and show that these modified cells contribute extensively to the somatic and germ-cell lineages in chimaeric mice. Compared with current methods for manipulation of the mouse genome, this approach has the advantage that powerful somatic-cell genetic techniques can be used to modify and to select cells with germ-line potential, allowing the derivation of transgenic strains with pre-determined genetic changes. We have by this means inserted many proviral vector sequences that provide new chromosomal molecular markers for linkage studies in the mouse and that also may cause insertional mutations.
TL;DR: The isolation of DNA clones complementary to the cellular messenger RNA transcripts of mdr genes are reported and it is shown that high-level expression of a full-length complementary DNA clone in an otherwise drug-sensitive cell confers a complete multidrug-resistant phenotype.
Abstract: The emergence and outgrowth of a population of tumour cells resistant to multiple drugs is a major problem in the chemotherapeutic treatment of cancer. We have used highly drug-resistant cell lines developed in vitro to study the molecular basis of multidrug resistance. In these cell lines high levels of resistance are frequently associated with amplification and overexpression of a small group of genes termed mdr (refs 1–3) or gp170 (ref. 4). Direct evaluation of the role of these genes in multidrug resistance has awaited the isolation of a member of this gene family in a biologically active form. Here we report the isolation of DNA clones complementary to the cellular messenger RNA transcripts of mdr genes and show that high-level expression of a full-length complementary DNA clone in an otherwise drug-sensitive cell confers a complete multidrug-resistant phenotype. Our results demonstrate that overexpression of a single member of the mdr group is sufficient to confer drug resistance. Furthermore, because the cDNA was isolated from a drug-sensitive cell, mutations in the primary sequence of mdr are not required to produce a multi-drug-resistance phenotype.
TL;DR: The amino-acid sequence of the precursor of the human tumour cell line-derived platelet-derived growth factor (PDGF) A-chain has been deduced from complementary DNA clones and the gene localized to chromosome 7, showing extensive homology to the PDGF B-chain precursor.
Abstract: The amino-acid sequence of the precursor of the human tumour cell line-derived platelet-derived growth factor (PDGF) A-chain has been deduced from complementary DNA clones and the gene localized to chromosome 7. The protein shows extensive homology to the PDGF B-chain precursor. Expression of the PDGF A-chain gene is independent of that of the PDGF B-chain in a number of human tumour cell lines, and secretion of a PDGF-like growth factor of relative molecular mass 31,000 correlates with expression of A- but not B-chain messenger RNA.
TL;DR: It is concluded that four extra, reading frame-restoring nucleotides are added during or after transcription of the frameshift gene by an RNA-editing process.
TL;DR: Experiments suggest a unified view of these apparently disparate types of gene regulation, which bind to sites on the DNA either nearby or at a considerable distance.
Abstract: Transcription of genes can be controlled by regulatory proteins that bind to sites on the DNA either nearby or at a considerable distance. Recent experiments suggest a unified view of these apparently disparate types of gene regulation.
TL;DR: The gene that is abnormal in the X-linked form of the phagocytic disorder chronic granulomatous disease has been cloned without reference to a specific protein by relying on its chromosomal map position.
Abstract: The gene that is abnormal in the X-linked form of the phagocytic disorder chronic granulomatous disease has been cloned without reference to a specific protein by relying on its chromosomal map position. The transcript of the gene is expressed in the phagocytic lineage of haematopoietic cells and is absent or structurally abnormal in four patients with the disorder. The nucleotide sequence of complementary DNA clones predicts a polypeptide of at least 468 amino acids with no homology to proteins described previously.
TL;DR: These vectors were utilized to eliminate an efficient transcriptional terminator of T7 RNA polymerase in the cDNA of bovine preproparathyroid hormone by oligonucleotide directed mutagenesis and changed the codon for phenylalanine-19 in the signal peptide to alanine.
Abstract: Chimeric phage-plasmid expression vectors were constructed from pUC18/19 plasmids by cloning a single-stranded DNA (ssDNA) origin of replication from bacteriophage f1 and inserting a bacteriophage T7 promoter within the beta-galactosidase gene. A T7 promoter permits in vivo or in vitro expression of single proteins by the translation of T7 RNA polymerase transcripts. Insertional inactivation of the T7 promoter-containing beta-galactosidase gene permits a simple blue-to-white color cloning assay. Compared with several helper phages that were examined, superinfection with M13K07 resulted in the highest yields of the pTZ plasmids as ssDNA viral particles. These ssDNA promoter plasmids are uniquely suited for protein engineering because they simplify cloning, oligonucleotide directed mutagenesis, verification by enzymatic sequence analysis, and expression of mutant proteins from a single vector. These vectors were utilized to eliminate an efficient transcriptional terminator of T7 RNA polymerase in the cDNA of bovine preproparathyroid hormone by oligonucleotide directed mutagenesis. The mutation changed the codon for phenylalanine-19 in the signal peptide to alanine. In a cell-free system the mutant cDNA transcripts were translated into preproparathyroid hormone, which was converted to proparathyroid hormone in the presence of microsomal membranes.
TL;DR: A DNA-binding gel electrophoresis assay was used to detect a protein(s) in HeLa cell nuclear extracts that specifically binds to the 5' activating element.
TL;DR: It is reported that electroporation-mediated DNA transfer of a chimaeric gene encoding neomycin phosphotransferase results in stably transformed maize cells that are resistant to kanamycin.
Abstract: The graminaceous monocots, including the economically important cereals, seem to be refractory to infection by Agrobacterium tumefaciens, a natural gene transfer system that has been successfully exploited for transferring foreign genes into higher plants. Therefore, direct transfer techniques that are potentially applicable to all plant species have been developed using a few dicot and monocot species as model systems. One of these techniques, electroporation, uses electrical pulses of high field strength to permeabilize cell membranes reversibly so as to facilitate the transfer of DNA into cells. Electroporation-mediated gene transfer has resulted in stably transformed animal cells and transient gene expression in monocot and dicot plant cells. Here we report that electroporation-mediated DNA transfer of a chimaeric gene encoding neomycin phosphotransferase results in stably transformed maize cells that are resistant to kanamycin.
TL;DR: A chicken oviduct cDNA clone containing the complete open reading frame of the oestrogen receptor (ER) has been isolated and sequenced, indicating that c‐erbA, the cellular counterpart of v‐erbB, belongs to a multigene family of transcriptional regulatory proteins which bind steroid‐related ligands.
Abstract: A chicken oviduct cDNA clone containing the complete open reading frame of the oestrogen receptor (ER) has been isolated and sequenced. The mol. wt of the predicted 589-amino acid protein is approximately 66 kd which is very close to that of the human ER. Comparison of the human and chicken amino acid sequences shows that 80% of their amino acids are identical. There are three highly conserved regions; the second and third of which probably represent the DNA- and hormone-binding domains of the receptor. The putative DNA-binding domain is characterised by its high cysteine and basic amino acid content, and the hormone-binding domain by its overall hydrophobicity. These two domains of homology are also present in the human glucocorticoid receptor (GR) and the product of the avian erythroblastosis virus (AEV) gene, v-erbA, indicating that c-erbA, the cellular counterpart of v-erbA, belongs to a multigene family of transcriptional regulatory proteins which bind steroid-related ligands. The first highly conserved ER region is not present in the truncated v-erbA gene, but shares some homology with the N-terminal end of the GR. The function of the v-erbA gene product is discussed in relation to its homology with the ER and GR sequences.
Patent•
06 Aug 1986TL;DR: In this paper, a cloning or expression vector comprising a gene which encodes 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) polypeptide was proposed.
Abstract: This invention involves a cloning or expression vector comprising a gene which encodes 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) polypeptide which, when expressed in a plant cell contains a chloroplast transit peptide which allows the polypeptide, or an enzymatically active portion thereof, to be transported from the cytoplasm of the plant cell into a chloroplast in the plant cell, and confers a substantial degree of glyphosate resistance upon the plant cell and plants regenerated therefrom. The EPSPS coding sequence may be ligated to a strong promoter, such as the 35S promoter from cauliflower mosaic virus, to create a chimeric gene. Such genes can be inserted into plant transformation vectors, and subsequently introduced into plant cells. Plant cells transformed using such genes and plants regenerated therefrom have been shown to exhibit a substantial degree of glyphosate resistance.
TL;DR: A bimodal mechanism of action for tat-III in the trans-activation of HIV-specific gene expression is suggested, and a marked increase in the steady state level of IL-2 mRNAs transcribed from the HIV LTR, and these m RNAs also demonstrated a specific enhancement of their translational efficiency.
TL;DR: The cloned receptor protein activates its corresponding enhancers, restoring to the receptor-deficient cells the full capacity for regulated enhancement.
TL;DR: Evidence is presented that multidrug-resistant sublines of human KB carcinoma cells, selected for resistance to either colchicine, vinblastine, or Adriamycin (doxorubicin), display amplification of two different DNA sequences homologous to the hamster mdr gene, suggesting that the mdr1 gene is involved inMultidrug resistance in human cells.
Abstract: The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that multidrug-resistant Chinese hamster cell lines contain an amplified, transcriptionally active DNA sequence designated mdr. This report presents evidence that multidrug-resistant sublines of human KB carcinoma cells, selected for resistance to either colchicine, vinblastine, or Adriamycin (doxorubicin), display amplification of two different DNA sequences homologous to the hamster mdr gene. Segments of the human mdr DNA sequences, designated mdr1 and mdr2, have been cloned. mdr1 sequences were amplified in all of the highly drug-resistant sublines and were expressed as a poly(A)+ RNA species of 4.5 kilobases that was detected in the resistant cells but not in the parental cell line. No expression of mdr2 sequences was detected. mdr2 sequences were coamplified with mdr1 in some of the multidrug-resistant sublines and, in two independently derived cell lines, underwent very similar rearrangements. The data suggest that the mdr1 gene is involved in multidrug resistance in human cells.