RESUMO
The pro alpha 1 (I) collagen structural gene (COL1A1), the acid alpha-glucosidase (GAA), and the thymidine kinase (TK) genes, known to be closely linked in man (HSA) and mapped to HSA17, were found syntenic in two Cercopithecoidae species, the baboon (Papio papio, PPA) and the African green monkey (Cercopithecus aethiops, CAE) and assigned to homoeologous chromosomes, PPA16 and CAE19, respectively. The assignment of COL1A1 was obtained using two human cDNA probes. Hind III restriction sites found in man were present in the two species. The particular CAE individual used in the experiment showed a polymorphism for one DNA fragment.
Assuntos
Cercopithecus/genética , Chlorocebus aethiops/genética , Mapeamento Cromossômico , Marcadores Genéticos , Papio/genética , Animais , Enzimas de Restrição do DNA , Genes , Humanos , Pró-Colágeno/genética , Especificidade da Espécie , Timidina Quinase/genética , alfa-Glucosidases/genéticaRESUMO
A cloned human cDNA for transferrin (TF) was used as hybridization probe in analysing a series of rodent x human somatic cell hybrids for the presence of human TF sequences. The assignment to chromosome 3 was further refined to region 3q21----3qter using hybrids that carried a translocated chromosome 3 and fibroblasts from a patient trisomic for this region. The gene for TF therefore maps to the same region as the gene for transferrin receptor (TFR) thereby defining an iron transport region on 3q2 to which the transferrin-related tumor associated antigen p97 may also belong. It follows that the genes for pseudocholinesterase (CHE1), ceruleoplasmin (CP) and alpha-2HS-glycoprotein (A2HS) which belong to the, as yet unassigned, linkage group of TF, now also map to chromosome 3 in man.
Assuntos
Cromossomos Humanos 1-3/ultraestrutura , Genes , Transferrina/genética , Animais , Mapeamento Cromossômico , Cricetinae , Cricetulus , DNA/genética , Fibroblastos/ultraestrutura , Humanos , Células Híbridas/ultraestrutura , Camundongos , Receptores de Superfície Celular/genética , Receptores da Transferrina , TrissomiaRESUMO
Non-random tumour-specific chromosomal abnormalities have been observed in cells of many different human tumours. In Wilms' tumour (WT) and retinoblastoma, a chromosomal deletion occurs germinally or somatically and has been considered an important step in tumour development. One class of potential cellular transforming genes comprises the cellular homologues of the transforming genes of highly oncogenic retroviruses. A remarkable concordance between the chromosomal location of human cellular oncogenes and the breakpoints involved in acquired chromosomal translocations is becoming apparent in various cancers: the oncogenes c-mos, c-myc and c-abl are located at the breakpoints that occur in acute myeloblastic leukaemia, Burkitt's lymphoma and chronic myelocytic leukaemia respectively. Thus when the oncogene c-Ha-ras1 was localized to the short arm of human chromosome 11 (refs 6-8; region 11p11 leads to p15 and not 11p13 as stated in ref. 5), it was proposed as a possible aetiological agent in the aniridia-WT association (AWTA) that results from a deletion of 11p13 (although a transforming gene recently isolated from a WT cell line (G401) was shown not to be homologous to either c-Ha-ras or c-Ki-ras9). We have now looked for deletion or rearrangement of c-Ha-ras1 in the DNA from four subjects with del(11p13)-associated predisposition to Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation. We report here that in no case is c-Ha-ras1 deleted, and we have further refined its location to 11p15.1 leads to 11p15.5. On the basis of enzyme studies and direct gene dosage determination for c-Ha-ras1 and beta-globin in neoplastic and non-neoplastic tissues from one patient, we conclude that deletion of the normal counterpart of 11p cannot account for the development of the tumour.
Assuntos
Cromossomos Humanos 6-12 e X , Iris/anormalidades , Neoplasias Renais/genética , Proteínas de Neoplasias/genética , Oncogenes , Tumor de Wilms/genética , Pré-Escolar , Deleção Cromossômica , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , Masculino , Linhagem , SíndromeRESUMO
We describe a new method of direct gene dosage determination in patients with unbalanced chromosomal aberrations using cloned DNA sequences: the intensity of the signal obtained by hybridization of the radioactive probe to the corresponding DNA fragments can be compared with the intensity of the DNA fragments that hybridize with a nonsyntenic probe used as an internal control. This has been demonstrated by densitometer tracing of the autoradiogram, using an X-specific DNA sequence, beta globin and alpha 2(I) collagen probes, in normal men and women, in one patient trisomic for 11p, and in one patient trisomic for segment 7q21 leads to 7qter. The ratio men/women for the X-specific sequence (DXS) was close to the expected value 0.5, while the ratio trisomy 11/normal control and trisomy 7/normal control were close to 1.5 for beta globin (HBB) and alpha 2(I) collagen (COLIA2), respectively. The gene coding for COLIA2 can therefore be assigned to 7q21 leads to 7qter. This method should also apply to noncoding sequences: the increasing number of cloned DNA segments that have already been assigned to a specific chromosome represent a new tool for prenatal and premorbid diagnosis of unbalanced chromosomal aberrations.
Assuntos
Alelos , Aberrações Cromossômicas , Cromossomos Humanos 6-12 e X , Pró-Colágeno/genética , Adolescente , Mapeamento Cromossômico , DNA Recombinante , Feminino , Globinas/genética , Humanos , Lactente , Masculino , Hibridização de Ácido Nucleico , Trissomia , Cromossomo XRESUMO
By in situ hybridization of normal human chromosomes with a cloned genomic probe specific for the constant region of the lambda immunoglobulin genes, band 22q11 was preferentially labelled. In two cell lines with t(8;22) derived from Burkitt's lymphoma a strong signal was noted on the 8q+ chromosome derivative, indicating that the constant region of the lambda Ig gene cluster was translocated from chromosome 22 to chromosome 8. In addition, the signal observed on the 22q- derivative chromosome was stronger than the background in one of the two cell lines tested, but not in the other. The implications are that the break point in chromosome 22 in some cases lies within the Ig gene itself or between clusters of such genes, and that different cases have different break points.
Assuntos
Linfoma de Burkitt/genética , Cromossomos Humanos 21-22 e Y , Cromossomos Humanos 6-12 e X , Genes , Regiões Constantes de Imunoglobulina/genética , Cadeias Leves de Imunoglobulina/genética , Cadeias lambda de Imunoglobulina/genética , Imunoglobulinas/genética , Translocação Genética , Linhagem Celular , Clonagem Molecular , Humanos , Hibridização de Ácido NucleicoRESUMO
A recombinant plasmid containing sequences complementary to human pro-alpha l(I) collagen mRNA was used for the chromosomal assignment of the pro-alpha l(I) collagen gene. Restriction endonuclease analysis of DNA from mouse-human and Chinese hamster-human somatic cell hybrids revealed cosegregation with human chromosome 17. Hybrids containing derivative chromosomes with a t(2;17)(q14;q21) translocation showed cosegregation of the pro-alpha l(I) gene with the segment 17q21 leads to qter. In situ hybridization on human metaphasic chromosomes confirmed this conclusion.