Showing papers in "Human Genetics in 1975"

Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. A novel approach to testing for induced point mutations in mammals.

Abstract: The protein-mapping method which combines isoelectric focusing in acrylamide gel and gel electrophoresis was previously used mainly for the separation of plant proteins and human serum proteins. We investigated with this technique soluble proteins of mouse tissues (whole embryos, the liver of fetal and adult mice, kidneys) and the proteins of mouse serum. The technique was tested under a number of different conditions to find those best for our purpose; they may represent some general improvements in the method. The protein patterns show high resolution and excellent reproducibility. About 275 spots were found for fetal liver, about 230 for whole embryos (day 14 p.c.) and about 100 for serum. The fact that a high number of protein spots can be evaluated by a single and comparatively simple experiment suggests that this method may be useful as an assay system for induced point mutations. The protein patterns demonstrated are compared and discgs of dominant lethal examinations after acute and subacute application of these three substances.

Incidence of chromosome aberrations among 11148 newborn children.

Abstract: Chromosome analysis has been made of 11148 children; 29 had sex chromosome abnormalities (260 per 1000) and 64 autosomal abnormalities (574 per 1000) The total incidence of major chromosome abnormalities was 834 per 1000 The incidence of chromosome variations was 168 per 1000 The most common variants were those with variation in size of short arms-satellites in D and G chromosomes and variations in Y chromosome size So far, very little is known about the significance of such chromosome variations The incidence of most chromosome abnormalities in liveborn children is well established by now from studies of a total of 54749 consecutively liveborn children in 6 studies as shown in Table 1 More chromosome studies of liveborn children are, however, needed for several purposes such as finding families with chromosome translocations, studying segregation rates and giving genetic advice to families with inheritable chromosome aberrations and an increased risk of getting children with unbalanced chromosome abnormalities, mental retardation and physical abnormalities One of the main purposes in chromosome examination of newborn children is to study the development of children with different chromosome abnormalities, especially those with sex chromosome abnormalities, and compare then with controls, treat them when needed and give advice to the parents of such children

Polymorphism of red cell glyoxalase I (E.C.: 4.4.1.5). A new genetic marker in man

Abstract: The polymorphism of glyoxalase I was investigated in 169 mother-child combinations from southwestern Germany. Glyoxalase I (GLO) has 3 common phenotypes: GLO 1, GLO 2-1, and GLO 2. The results are in good agreement with the formal hypothesis: Two alleles GLO1 and GLO2 at an autosomal locus. The GLO1 gene frequency was estimated to be 0.39. From the electrophoretic pattern the GLO-molecule appears to consist of two subunits.

Late replicating bands of human chromosomes demonstrated by fluorochrome and Giemsa staining.

Abstract: The addition of thymidine (TdR) to cells growing in a medium containing 5-bromodeoxyuridine (BUdR) at the end of the first replication cycle results in the incorporation of TdR into the late replicating DNA regions. These sites can be visualized by staining the metaphase chromosomes with the fluorescent dye “33 258 Hoechst” or a “33 258 Hoechst” Giemsa procedure. A sequence of late replication patterns has been established in metaphase chromosomes of cultured human peripheral lymphocytes. The patterns are in agreement with those obtained by the standard autoradiographic procedures, but are more accurate. As is known from autoradiography, late replicating bands are in the position of G or Q bands. The “33 258 Hoechst” Giemsa staining procedure of chromosomes which have replicated in the presence of BUdR first and in TdR for the last 2 hrs of the S phase is preferable to the currently used Giemsa banding techniques: the method yields very well banded metaphases in all preparations examined, as the chromosome structure is not disrupted by the pretreatment. The bands are very distinct, even in the “difficult” chromosomes (e.g No. 4, 5, 8, and X). In female cells the late replicating X chromosome can be identified by its size and staining pattern. In addition to the replication asynchrony, the sequence of replication within both X chromosomes in female cells is not absolutely identical. The phenomenon of a phase difference in replication between the homologues is not a peculiarity of the X chromosome, but can be found in all autosomes as well as in homologous positions on the chromatids of individual chromosomes.

Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipatrophic diabetes

Abstract: A female patient with the following symptoms has been observed: complete absence of subcutaneous fat on the arms and legs, well developed adipose tissue on the trunk and face, severe hyperlipidemia, eruptive xanthomas, insulin resistant diabetes mellitus with lack of ketoacidosis, hepatomegaly and elevated basal metabolic rate. The patient thus exhibited all characteristics of lipatrophic diabetes (Lawrence type of diabetes).

Association of pericentric inversion of chromosome 9 and reproductive failure in ten unrelated families.

Abstract: A pericentric inversion of chromosome 9 has been detected in 10 unrelated families. The break points are identical and the inversions involved the heterochromatic segment. The effects of inversion of chromosome 9 on different aspects of reproductive failure are discussed.

The human leukocyte test system. VI. The use of sister chromatid exchanges as possible indicators for mutagenic activities.

Abstract: The trifunctional alkylating chemical mutagen trenimon increases the frequency of sister chromatid exchanges in human leukocyte chromosomes in vitro, as revealed by a BUdR-Giemsa method. Treatment with lead acetate exhibited negative results in this respect. The use of sister chromatid exchanges as possible indicators for mutagenic activities is discussed.

Linkage group HL-A-MLC-BF (properdin factor B). The site of the Bf locus at the immunogenetic linkage group on chromosome 6.

Abstract: Genetic linkage between the HL-A and Bf loci could be confirmed in 43 families with 168 offspring. In 4 families, 5 recombinants out of 82 informative meiotic divisions were observed (r=6.1%). The localisation of the Bf marker system was studied in 3 families with crossovers between HL-A and MLC. From these data the following map order of human chromosome 6 can be proposed: HL-A (1st locus) —HL-A (2nd locus)—MLC-Bf---PGM3. The fact that important components of the classical and alternate pathway of complement activation are governed by genes closely linked with HL-A and MLC loci leads to the proposition to include the Bf system into the Major Histocompatibility Complex in man.

On the mutation rate of neurofibromatosis

Abstract: A genetic study of 124 cases of neurofibromatosis was performed. The contingent of probands was mainly represented by a Russian population, most of the individuals being born in the European part of the RSFSR. Both parents of the probands were examined in only 58 cases, the proportion of sporadic cases in this group being 0.79, as compared to 0.77 for the whole group under study. The existing data evaluated by a direct method are not yet sufficient for a decisive estimation of the penetrance, which, however, cannot be under 80%. Segregation analysis of descendants from particular marriages showed a good correspondance to the hypothesis of Mendelian dominance (32 affected children out of 65). These results analyzed together with those obtained by other authors permit an inference on the full penetrance of neurofibromatosis. The genetic interpretation of sporadic cases as a result of new mutations is presented. The prevalence of neurofibromatosis among the 16-year-old youths was evaluated as 12.8 · 10-5. This value is suggested to be an estimation of the incidence of the condition in the general population, the mutation rate evaluated by a direct method being equal to 4.4 · 10-5÷4.9 · 10-5. The increased birth order of probands in sporadic cases (against the theoretical expectation) as well as increased paternal age (as compared with controls) were found to be statistically significant (P=0.004 andP=0.03, respectively) while the difference in maternal ages was statistically insignificant (P=0.08). No statistical relationship between sporadic cases and occupational exposure of parents to deleterious chemical and physical factors was found.

Frequency and distribution of sister-chromatid exchanges in a case of Fanconi's anemia

Abstract: In lymphocytes of a 7-year-old boy with Fanconi's anemia the frequencies and sites of sister-chromatid exchanges (SCE) were studied with the BrdU-Giemsa method. The average frequency of SCE (8.8 per metaphase) and the inter-and intrachromosomal distribution of SCE was not significantly different from the controls.

A mechanism of x chromosome aneuploidy in lymphocytes of aging women.

Abstract: One and sometimes both X chromosomes in cultured lymphocytes of women donors showed division of the centromere when the centromeres of other chromosomes were entire. This premature centromere division (PCD) was associated with evidence of nondisjunction of the X chromosome. On average, 2% of metaphases from 32 women donors showed PCD, but the incidence was 4 times greater in women over 59 years of age than in women under 40 years. Increased X chromosome aneuploidy was associated with the higher frequency of PCD in cultured lymphocytes from older women. PCD of the X chromosome is considered to be the mechanism of non-disjunction causing the previously described aneuploidy in cultured lymphocytes of aging women.

Chromosomal damage in chronic alcohol users.

Abstract: First in vitro mitoses were analysed from the peripheral leukocytes of 22 chronic alcohol users and of 18 controls. The frequency of exchange aberrations of the chromatid and chromosome type were significantly higher in the alcohol as compared with the control group. The results indicate an indirect or direct mutagenic activity of alcohol in vivo.

The rate of sister chromatid exchanges parallel to spontaneous chromosome breakage in Fanconi's anemia and to trenimon-induced aberrations in human lymphocytes and fibroblasts.

Abstract: The incidence of structural chromosome aberrations and the rate of sister chromatid exchanges (SCE) was investigated in lymphocyte cultures from a patient with typical Fanconi's anemia and his parents. The rate of SCEs was found to be normal. In experiments with the alkylating agent Trenimon the SCE rates proved to be a sensitive indicator for the induction of structural aberrations: in presence of an induced aberration rate half as high as the spontaneous rate in the Fanconi's anemia case, the rate of SCEs was found to be quintupled. Dose-effect relationships for the induction of SCE rates by Trenimon were studied over a wide dose range in lymphocyte and fibroblast cultures. The results reflect the same difference in sensitivity earlier observed in the induction of structural chromosome aberrations, fibroblasts being far more sensitive.

The G-banded prophase chromosomes of man.

Abstract: Using a simple G-banding technique developed in our laboratory, analysis of late prophases enables the visualization of approximately 1000 bands in the haploid set of human chromosomes. These bands have been classified according to the recommendations of the Paris Conference. The increased resolution offered by this technique is likely to be useful in the study of the structure and molecular organization of chromosomes and in identifying minute chromosome defects in birth defects and neoplasia.

Extra-Hepatic Storage of Copper* A Male Foetus Suspected of Menkes' Disease

Abstract: The distribution of copper among the organs of an aborted, male foetus, expected to develop Menkes' syndrome, was entirely different from the distribution in 4 normal foetuses. Copper concentrations determined by neutron activation analysis showed a considerably reduced content in the liver, but increased concentrations in the other organs analysed; total foetal copper was normal.

Partial trisomy 9q: A new syndrome

Abstract: Two unrelated patients with a strikingly similar phenotype (low birth weight and poor thriving; mental retardation; dolichocephaly; beaked nose; deeply set eyes; prominent maxilla and receding small chin; long fingers with a peculiar clench) were partially trisomic for two different segments of 9q. The segment found to be trisomic in both patients is small and corresponds to the q31q32 region. This new syndrome is compared to observations of trisomy 9 reported in the literature.

Cultivated cells from diagnostic amniocentesis in second trimester pregnancies

Abstract: Four independent fetal urine specimens yielded clonal growth. The mature colonies were similar to certain classes of amniotic fluid cell clones, and to those obtained from fetal kidney. Kidney specific LDH isozyme patterns, however, were not observed in any of these primary clones.

Tandem duplication q14 and dicentric formation by end-to-end chromosome fusions in ataxia telandiectasia (AT). Clinical and cytogenetic findings in 5 patients.

Abstract: Chromosome studies on lymphocyte cultures were performed in 5 patients with AT, 2 of whom had been followed for 4 years. Four out of these patients showed an increased incidence of chromosome-type aberrations. A clonal development was present in one patient, 96% of his metaphases containing a tandem duplication of almost the entire long arm 14. Four years earlier the proportion of these cells was 80%. Two other patients presented a small proportion of cells with an unidentified abnormally long D chromosome. In a total of 724 metaphases from 4 patients 31 dicentric chromosomes were observed, all of a peculiar type: in their formation no chromosome material was lost and they all seem to have arisen by end-to-end fusions. The incidence of chromatid-type aberrations was normal or at the upper limit of control values in all 5 cases. The sister chromatid exchange rate studied with BUDR in 3 patients was found to be normal.

Two complex translocations in chronic granulocytic leukemia involving chromosomes 22, 9, and a third chromosome

Abstract: Among 13 Ph-positive cases of chronic granulocytic leukemia (CGL), banding studies revealed two with complex rearrangements involving translocation of the long arm of number 22 to another autosome and a segment of that chromosome translocated to the long arm of number 9. In a patient with both CGL and sickle cell anemia, the 3-way rearrangement involved chromosomes 5, 9, and 22; and he also had a second Phildaelphia chromosome and two constitutional variants: pericentric inversion of the other number 9 chromosome and satellite polymorphism in the G group. The karyotype of the leukemic cells was interpreted as: 47,XY,inv(9) (p11q13),t(5;9;22)(q13;q34;q11)+del(22)(q11).

Cytogenetic studies in 12 patients with Itai-Itai disease

Abstract: Among 12 Itai-Itai disease patients examined, 8 patients showed a remarkably high frequency of chromatid aberrations, whereas the other 4 patients showed a much lower frequency of such aberrations, although a significant number of stable type aberrations was observed also in the latter patients. The frequencies of aneuploid cells of all 12 patients were significantly higher than those of the controls. The abnormalities were found in 50-hour and 72-hour cultures, from which it can be concluded that the aberrations occurred in the blood stem cell of the patients. In addition to these structural and numerical aberrations, satellite associations of the D and G group chromosomes were often observed.

Porokeratosis [correction of Parakeratosis] Mibelli and skin carcinoma: a critical review.

Abstract: The literature on parakeratosis Mibelli (PM) is revised critically with respect to the development of skin carcinoma. The incidence of epidermal malignancies in PM lesions is 7% (17 of 250 cases). An influence of X-ray treatment is not excluded in 4 cases with tumors in PM.

Human karyotype polymorphism

Abstract: In the article the results of a parallel routine and fluorescent investigation of chromosomes in 103 normal individuals (51 women and 52 men) are presented There were no gross chromosomal abnormalities in the individuals studied, but in 30 (291%) of them various autosomal variants (1q+, 9q+, 16q+, 17ph+, Dp+, Gp+, et al) were detected by the routine method Five men (95%) had Y chromosome variants The authors were successful in identifyng practically all these chromosomal variant by their fluorescent banding patterns The occurrence of brilliant fluorescent bands in chromosome parts showing variable fluorescence (paracentromeric area of chromosome 3, short arms and satellites of acrocentric chromosomes and the distal part of Y chromosome) was also investigated Some questions connected with karyotype polymorphism in man are discussed

Structural aberrations of chromosome 18. II. The 18q- syndrome. Report of three cases.

Abstract: 3 cases of the 18q — syndrome, 2 boys and 1 girl, are presented, and a comparison with data from the literature is given. The following features are typical of the syndrome: short stature, mental retardation, muscular hypotonia, a peculiar dysmorphia of the face and ears, cryptorchidism and small scrotum in males, proximally implanted thumbs, tapering fingers, excess of whorls on the fingertips, and dorsally implanted second toes. Midface hypoplasia with hypertelorism and cleft palate, as well as strabismus, were present in 2 of our patients, whereas all 3 showed nystagmus and prominence of anthelix and antitragus. In addition, 2 patients exhibited narrow ear canals and impaired hearing. One patient had coloboma of the iris and choroid, pale optic discs, and cleft lip; another had umbilical and inguinal hernias. Two cases represented de novo deletions of the long arm of chromosomes 18, whereas the karyotype of the father of the third case revealed a balanced translocation t(15;18)(q24;q21).

Biochemical and cytogenetic studies on the nucleolus organizing regions (NOR) of man. II. A family with the 15/21 translocation.

Abstract: The amount of ribosomal DNA (rDNA) was determined quantitatively by RNA-DNA hybridization in the genomes of a mother and her daughter, both with the karyotype 45,XX,t(15q21q). The saturation values found were 0.030% (mother), 0.023% (daughter), and 0.022% for the husband and father of the daughter. A detailed cytogenetic analysis of the short arms of the acrocentric chromosomes of these probands allowed the biochemical results to be interpreted in terms of the size of the individual set of nucleolus organizing regions (NORs) present in each proband. The correlation existing between the biochemical and the cytogenetic findings shows that the amount of rDNA in the human genome is not primarily a function of the number of acrocentric chromosomes, but depends on the individual combination of variant NORs occurring in the human genome.

The Bf locus in the HLA region of chromosome 6: linkage and association studies.

Abstract: Bf allele frequencies in a material of 172 unrelated Norwegians are given. Bf/HLA linkage relations in 49 informative matings with 178 children, and Bf/HLA association data of a material of 212 Bf-HLA haplotypes are presented. Of 171 informative meioses, there were no Bf-HLA-B recombinations, while 3 out of 158 Bf-HLA-A informative meioses showed recombination. There is significant association between the BfF and the HLA-BW 35 allele.

Uneinheitlicher Phänotyp bei Partialtrisomie 4q

Abstract: Es wird uber die klinischen und cytogenetischen Befunde bei 3 nichtverwandten Patienten mit Partialtrisomie 4q berichtet. In 2 Fallen ist die Chromosomen-aberration durch eine balancierte elterliche Translokation entstanden (t(3p+;4q-) und t(4q-;18q+)) wahrend im 3. Fall eine spontane invertierte Insertion von 4q22→q34 in 4q34 angenommen wird.

A technique for in situ karyotyping of primary amniotic fluid cell cultures.

Abstract: A time proven technique is described for growing amniotic fluid cell cultures on cover glasses in Leighton tubes and for processing the mitotic cells in situ. Karyotyping the clones in situ eliminates most of the problems caused by somatic chromosome mutations in vitro and by maternal cell growth.

Frequency of inborn errors of metabolism, especially PKU, in some representative newborn screening centers around the world: A collaborative study

Abstract: It becomes quite clear, by comparing reliable data about frequencies of some inborn errors of metabolism in newborn populations scattered around the world, that the frequency of PKU is significantly different in different nations and races. For several of these differences the relationships and dissimilarities in the origin of present-day nations can be presumed as explanations. The examples of intra-Irish differences and those between Ashkenazi Jews and other European nations, demonstrate the possible effect of religious and social barriers. In Galactosemia by transferase deficiency, comparable observations can be made, although technical problems produce artefacts. At present there is no indication that Histidinemia has a different frequency in different parts of the world, but more data are needed. This is true also for Arginino-succinic-aciduria and Hartnup's disease where interesting differences in frequency have been observed but in too few screening centers.

[Four new cases of X-autosome translocation in man (author's transl)].

Abstract: Quatre nouveaux cas de translocation du chromosome X sont rapportes. L'un est une t(1;X) equilibree observee chez une fille anormale. Dans la plupart des cellules, l'X normal est inactive. Le second concerne une femme spaniomenorrheique ayant fait deux fausses couches. Elle porte une t(X-autosome) desequilibree. Dans toutes ses cellules, l'X anormal est inactive, ainsi que le segment autosomique en exces. Les troisieme et quatrieme cas sont familiaux. Il s'agit d'une t(XX) chez la mere, spaniomenorrheique, transmise a son fils dont le comportement psychologique semble anormal. La formule chromosomique de la mere est 46,X,+der t(XX) et celle du fils: 47,XY,+der t(XX). L'element anormal est inactive dans toutes les cellules.

The human leulocyte test system. VII. Further investigations concerning micronucleus-derived premature chromosome condensation.

Abstract: Premature chromosome condensation (PCC) from X-ray induced micronuclei shows a dose-effect relationship in human leukocytes in vitro. Preparations at different culture times without colcemide treatment reveal complex variations of the frequencies of micronuclei and PCC correlated with the fixation time. The positions of PCC patches in the metaphase plate and the frequencies of different PCC types (S and G2) ar independent on the X-ray dose. The latter indicates that the slowing down of the micronuclei in the cell cycle, which is the reason for the formation of PCC, may be an outcome rather of a regulatory phenomenon than of an unspecific physiological damage of the chromatin included in the micronuclei. This is especially evident from labeling experiments with tritiated thymidine, showing that the extent of asynchrony between main nuclei and micronuclei is independent on the X-ray dose. Labeling experiments with tritiated uridine reveal a X-ray dose dependent suppression of RNA synthesis in cells with main nuclei and micronuclei. THE S-phase nature of "pulverized" PCC patches could be verified by incorporation of tritiated thymidine in aound 50%. Staining of centromeric heterochromatin in micronuclei reveal a frequency of micronuclei with centromeric heterochromatin resembling the frequency of G2-phase PCC found in mitoses.