Biomedical subjects
Publications and source records attributed to C Junien.
We have used a cloned cDNA probe for human apolipoprotein CII (apo CII) and Southern blotting techniques to identify the human apo CII gene in DNA from a series of rodent X human somatic cell hybrids. Our results provide evidence for the assignment of this gene to human chromosome 19.
Three patients (two females, one male) are reported with bilateral aniridia, Wilms' tumor, more or less moderate mental retardation, decreased catalase activity, and del 11p13. These and 34 case reports from the literature are discussed with respect to: sex ratio, maternal age, type of chromosomal imbalance and frequency of associated rearrangements, prevalence of aniridia and other eye disorders, predisposition to tumor development, genitourinary anomalies, growth and mental retardation, and catalase involvement. Possible gene relationship within the complex locus and with neighbouring 11p genes is discussed.
We used cloned cDNA probes for the A alpha-, B beta-, and gamma-chains of human fibrinogen and Southern blotting techniques to analyze DNA from a series of rodent X human somatic cell hybrids for the presence of specific fibrinogen-related sequences. Our results provide evidence for the assignment of the three genes for fibrinogen to chromosome 4. Moreover, by direct gene-dosage determination in two patients with chromosome 4 unbalanced rearrangements, we refined the regional chromosomal assignment to 4q2, thus suggesting that these three genes whose expression is coordinately regulated are closely linked.
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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.
We have previously mapped the gene coding for catalase to 11p13 by gene dosage analysis. Deletion of this chromosomal region causes aniridia, mental retardation, and predisposition to Wilms' tumor (WT). In the present study, 22 patients with various etiologic forms of WT and/or aniridia were investigated. The catalase (CAT) level and karyotype were examined in order to determine the linkage and the gene ordering on chromosome number 11 of the different loci involved. The CAT concentration was normal in the 19 cases without detectable chromosomal abnormalities.
All prometaphase constitutional karyotype from 13 patients with isolated whose tumor were normal, without 11p13-p14 anomaly Catalase determination showed normal results.
A 17-year-old girl with a severe mental retardation and facial dysmorphism was found to be carrier of an abnormal chromosome no. 13. Her mother and several other members of her family carry a pericentric inversion of chromosome no. 13. The abnormal 13 of the proposita was shown to result of "aneusomie de recombinaison" of the inverted chromosome no. 13. Biochemical, hematological, and clinical features contribute to the establishment of the clinical map of chromosome 13.
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.
A report by Bullock and coworkers has emphasized the need for standardization of the CK assay in carrier detection for DMD. A collaborative study, according to a well-specified design and involving two laboratories in Paris and Lyon, indicates that the reliability of this assay can be improved provided that special attention is paid to information about participating subjects, laboratory protocol, and repeated sampling. On a random sample of young women, mean and variance of ln(CK) are 1.66 and 0.015 respectively. Within and between variance components are in a 3:4 ratio, homogeneous between populations. Additional use of a common test serum should insure good reliability of this assay among laboratories.
Esterase D (ESD) gene dosage studies were performed on amniotic cells from a fetus at risk for del 13q14. The mother was a balanced carrier of an insertion in chromosome #20: 46,XXins(20;13)(p12;q1307q14.3). She had already given birth to a monosomic child with retinoblastoma (Rb) and to a phenotypically normal child trisomic for the same 13q14 segment. Both sibs displayed the expected proportionate gene dosage effects for ESD. A 153% value of ESD activity was found in the amniotic cells indicating unambiguously that the fetus was not monosomic for segment 13q14 and therefore not at increased risk for Rb. The mother delivered a phenotypically normal child who was confirmed to be trisomic for segment 13q14 by cytogenetic analysis and by gene dosage studies for ESD in cord blood cells and in lymphoblastoid cells.
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.
A field study of glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin polymorphisms was performed in 327 subjects belonging to the Kel Kummer, a highly inbred Tuareg tribe of North-East Mali, and to the contact populations. In the Kel Kummer group 11% of the investigated subjects carried the nondeficient G6PD A+ variant. No other G6PD variant was found. Hemoglobin D Ouled-Rabah was found in 21% of the subjects of this group. The presence of an alpha-thalassemic trait was also inferred from indirect evidence. The contact groups (Inedän, Iklan, Kel es Suq and Dausahaq) exhibited different polymorphisms at the G6PD and globin loci, substantiating their belonging to different ethnic stock.
A cDNA for the pro alpha 2 chain of human type I collagen has been recently cloned and amplified. We have used this specific probe to identify the human chromosome carrying the pro alpha 2(I) collagen gene. The DNA from 17 independent human/hamster and human/mouse somatic cell hybrids was digested by Eco RI and the restriction pattern analyzed in Southern blot experiments, using the 32P-labeled cDNA as a hybridization probe. The gene coding for the pro alpha 2 collagen subunit could be unambiguously assigned to human chromosome 7. All the other chromosomes, including chromosome 17, were excluded.
Human phosphoglycerate mutase (PGAM, EC 2.7.5.3) is under the control of two structural loci that code for subunits A and B. By means of gene-dosage studies, Bücher et al. (1980) have assigned the loci for GOT1 and PGAMA to chromosome 19 of Mus musculus. Because of the known homologies between human and murine chromosomes, gene dosage studies were carried out in erythrocytes from one patient trisomic for the entire band 10q26 and from another patient monosomic for 10q26.2 and q26.3. Results were compatible with the assignment of PGAMA and GOT1 to 10q26.1 (or 10q25.3).
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Two patients with an inverted duplication of bands 8p21-p23 are described. The gene for glutathione reductase (GSR; E.C.1.6.4.2) has previously been localized to band 8p21. In one of the patients subband 8p21.1 was included in the duplication; GSR activity in the red blood cells was increased. In the other patient, subband 8p21.1 was not included in the duplication and GSR activity was normal. This allows GSR to be assigned to subband 8p21.1. Including the present 2 patients, at least 13 cases of this abnormality have been published. We have obtained data on at least 8 further cases (unpublished). We conclude that inv dup (8p) is a non-randomly occurring de novo structural aberration in man. The GSR results in our cases prove that breakpoints can be different in different patients. Clinical symptoms and signs include some common features but show marked interpatient variation which should, at least in part, be caused by the differences in break-points. A detailed collaborative study to determine the clinical and epidemiological features of this entity is recommended.
Prenatal diagnosis of congential enzymopenic methaemoglobinaemia (CEM) with mental retardation was performed in two fetuses at risk for generalized NADH-cytochrome b5 reductase deficiency. In the first case the enzyme activity of cultured amniotic cells was in the heterozygous to normal range. The mother delivered a normal baby with normal enzyme activity in cord blood cells. In the second case, the amniotic cells were almost completely enzyme deficient. The pregnancy was terminated, and the diagnosis of homozygous NADH-cytochrome b5 reductase deficiency was confirmed in cord blood cells, in several different tissues and in cultured fibroblasts from the aborted fetus.