Showing papers in "Human Genetics in 1976"
TL;DR: It is suggested that on the distal portion of the nonfluorescent segment of the long arm of the Y, factors are located controlling spermatogenesis.
Abstract: A deletion of the Y chromosome at the distal portion of band q11 was found in 6 men with normal male habitus but with azoospermia. Five of them were found during a survey of 1170 subfertile males while the sixth was karyotyped because of slight bone abnormalities. These findings, together with a review of the literature, suggest that on the distal portion of the nonfluorescent segment of the long arm of the Y, factors are located controlling spermatogenesis.
926 citations
TL;DR: The silver staining procedure for NOR's was simplified and standardized through control of the chemical and physical conditions during silver impregnation and developing.
Abstract: A reliable technique for staining human chromosomal nucleolar organizers (NOR's) with silver solutions is described. The NOR's can be selectively stained dark brown by silver solutions leaving the chromosome arms unstained and available for counterstaining with orcein or Giemsa dyes. Unequivocal identification of chromosome pairs bearing NOR's can be achieved using fluorescent banding techniques followed by silver staining. The silver staining procedure for NOR's was simplified and standardized through control of the chemical and physical conditions during silver impregnation and developing.
549 citations
TL;DR: The karyotypes of 941 singleton and 42 twin abortuses and 4 cystic placentae were determined and an attempt was made to relate the karyotype of the conceptus to its subsequent development.
Abstract: The karyotypes of 941 singleton and 42 twin abortuses and 4 cystic placentae were determined. 30.5% of the singletons were chromosomally abnormal; 49.8% of these were trisomic, 23.7% X-monosomics and 17.4% polyploid. 143 trisomies were identified by banding; over a third had an extra chromosome 16, more than 10% and extra 21 or 22 and about 5% an extra 2, 18 or 15. Examples of trisomy 3, 4, 8, 9, 10, 13, 14 and 20 were also encountered. Using the data from two other published studies, the prevalence of different trisomies was estimated and an attempt was made to relate the karyotype of the conceptus to its subsequent development.
228 citations
TL;DR: The formal genetics of Fanconi's anemia were investigated on the basis of 21 families from different European countries, and of 69 families from the literature, and a high intrafamilial correlation for age at onset, and number and severity of malformations points to genetic heterogeneity.
Abstract: The formal genetics of Fanconi's anemia were investigated on the basis of 21 families from different European countries, and of 69 families from the literature. Conclusions:
181 citations
TL;DR: There were 18 individuals found to have a constitutional chromosome fragility causing an increase in break frequency, and the six constitutional chromosomal fragilities of the X chromosome had in common the association of mental deficiency, delayed speech, and large malformed ears.
Abstract: There were 18 individuals found to have a constitutional chromosome fragility causing an increase in break frequency. For each chromosome the breakpoint is always the same, whether it involves chromosomes from the same person, the same family, or different families. The fragile points are bands 10q24, 12q13, 16q21, 17p12, and Xq27. Autosomal constitutional fragility does not seem to have a phenotypic correspondence. They were found mostly in parents of children with chromosomal abnormalities or in couples with a history of repeated spontaneous abortions which permits one to raise the possibility of an interchromosomal effect. The six constitutional chromosomal fragilities of the X chromosome had in common the association of mental deficiency, delayed speech, and large malformed ears. The break points in constitutional chromosomal fragility were compared to those of spontaneous breaks in vitro, to those induced by X-rays, and to those in Fanconi's anemia. The theoretical consequences of these structural abnormalities are discussed as well as what to do about them when they are found.
133 citations
TL;DR: Patients with abnormal karyotypes who were referred to the Department of Medical Genetics with the possible diagnosis of Turner syndrome and the frequency of chromosomal abnormalities and clinical findings in the different chromosomal types are summarized.
Abstract: One hundred and ten patients with abnormal karyotypes who were referred to the Department of Medical Genetics with the possible diagnosis of Turner syndrome were reviewed. The frequency of chromosomal abnormalities and clinical findings in the different chromosomal types are summarized.
133 citations
TL;DR: In human leukocyte cultures set up with TC medium 199, DNA synthesis and mitotic indices were analysed by means of 3H-thymidine autoradiography and cell counting and revealed that first, second and third mitoses occur together in the cultures at this time.
Abstract: In human leukocyte cultures set up with TC medium 199, DNA synthesis and mitotic indices were analysed by means of 3H-thymidine autoradiography and cell counting. DNA synthesis starts at around 28 hrs. The frequencies of labelled cells rise slowly and reach a maximum of around 24%. The first mitoses appear at around 38 hrs but up to 49 hrs only very few mitoses can be seen. After that time the mitotic indices rise and reach values of up to 11‰. Cultivation in the presence of BUdR for 72 hrs and staining with Hoechst 33258 stain revealed that first, second and third mitoses occur together in the cultures at this time. Irradiation of whole blood and cultivation for 72 hrs leads to mitoses containing dicentric and ring chromosomes with an without fragments, to interphases with micronuclei, to premature chromosome condensations (PCC) and to polyploid mitoses indicating that at this time first and further mitoses are present.
131 citations
TL;DR: Four 46,XY siblings with congenital bilateral megalorchidia, macrogenitosomia, and severe mental deficiency were investigated and demonstrated the existence of normofunctional testicular hyperplasia.
Abstract: Four 46,XY siblings with congenital bilateral megalorchidia, macrogenitosomia, and severe mental deficiency were investigated. The testicular size was significantly larger than age-matched normal males. A normal hypothalamic-pituitary gonadotropin function was demonstrated by the finding of normal levels of luteinizing and follicle-stimulating hormones in blood samples drawn at frequent intervals and by normal responses to gonadotropin-releasing hormone and testosterone adminstration. A normal testicular function was shown by the finding of normal (a) plasma testosterone and estradiol levels, (b) gonadal response to human chorionic gonadotropin, (c) sperm analysis, and (d) morphology and cell architecture of the testes. Adrenal function was found to be within normal limits. These results demonstrated the existence of normofunctional testicular hyperplasia. The family studies suggested that this distinct congenital disorder is inherited as an X-linked recessive trait.
117 citations
TL;DR: A sensitive, reliable, and easily performed procedure is described for the prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism using cultured amniotic cells and skin fibroblasts.
Abstract: A sensitive, reliable, and easily performed procedure is described for the prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism using cultured amniotic cells and skin fibroblasts. With this assay, control fibroblast lines incorporated a mean of 6.89 nanoatoms 14C/mg protein from [1-14C]propionate into trichloroacetic acid (TCA)-precipitable cell material in 10h. Twenty-five mutant fibroblast lines from patients with propionicacidemia or one of the methylmalonicacidemias fixed 0.04 to 0.93 nanoatoms 14C/mg. Considerable variation was observed, both among and within discrete mutant classes, with respect to the residual amount of propionate pathway activity, possibly reflecting further molecular heterogeneity in these disorders.
108 citations
TL;DR: Findings not only confirm the assignment of the AK-1 locus to chromosome 9 made previously in somatic cell hybrids, but suggest a more precise assignment to region 9q33→qter.
Abstract: Quantitative red cell adenylate kinase (AK-1) assay has been used in 8 patients with partial duplication or deletion of chromosome 9 in an attempt to find the precise intrachromosomal location of the structural gene locus. All regions of chromosome 9 are represented in abnormal dosage in at least one patient. A 43% increase in AK-1 activity was found to be associated with duplication of the terminal band of the long arm of chromosome 9. Duplication of all other parts of chromosome 9 were associated with normal enzyme activity. These findings not only confirm the assignment of the AK-1 locus to chromosome 9 made previously in somatic cell hybrids, but suggest a more precise assignment to region 9q33→qter. This places the ABO: Np-1: AK-1 linkage group at the distal end of the long arm of chromosome 9.
102 citations
TL;DR: A new type of hemoglobin F, in which isoleucine in position 75 (E 19) of the γ chain is replaced by a threonine residue, has been found in 29 out of 32 homozygotes for β thalassemia.
Abstract: A new type of hemoglobin F, in which isoleucine in position 75 (E 19) of the γ chain is replaced by a threonine residue, has been found in 29 out of 32 homozygotes for β thalassemia. The amount of this hemoglobin ranges from traces to 40% of the total Hb F. The same γ75 Thr chain is also present in the Hb F of 40% of normal newborns and premature infants examined, of one 14-week-old fetus and in one out of 3 patients with aplastic anemia and raised levels of Hb F. Our results strongly suggest that the synthesis of this new chain is under the control of a γ gene nonallelic with those coding for Aγ and Gγ chains.
TL;DR: The 5-ACR is introduced in human lymphocyte cultures and does not induce chromatid asymmetry, as BrdU does, which constitutes a new argument for considering that the segmentation and the asymmetry of chromatids depend, at least partly, on two different mechanisms, where proteins are probably involved.
Abstract: The 5-ACR (5-azacytidine) introduced in human lymphocyte cultures induces a lack or a delay of condensation of some chromosome segements corresponding to the G-bands. The resulting R-banding is very similar to that obtained with a 7-h treatment by BrdU, although the segmentation may be much stronger (pulverization) with high doses. However, the 5-ACR does not induce chromatid asymmetry, as BrdU does. This constitutes a new argument for considering that the segmentation and the asymmetry of chromatids depend, at least partly, on two different mechanisms, where proteins are probably involved. Another effect of 5-ACR is to increase chromosome associations by satellites, secondary constrictions, and telomeric regions.
TL;DR: A trisomy 9 syndrome is delineated, consisting of features of the tr isomy 9p syndrome and various other malformations that include abnormalities of the cardiovascular and urogenital systems, cranial suture anomalies, dislocation of the hips and knees and early death.
Abstract: Two infants with trisomy involving chromosome 9 are described. One had complete trisomy 9 and the other karyotype 47,XX,+der(9),t(7;9)(p22;q32)mat. A trisomy 9 syndrome is delineated, consisting of features of the trisomy 9p syndrome and various other malformations. These include abnormalities of the cardiovascular and urogenital systems, cranial suture anomalies, dislocation of the hips and knees and early death. A possible relationship of some of these findings to regions of 9q involved in cases of partial trisomy 9 is suggested.
TL;DR: The total incidence of major chromosome aberrations including numerical changes of the sex chromosomes, and structural changes of autosomes, was 0.54% and about 0.75% of the newborn infants were found to have a variable bright fluorescent band located on the proximal area of the short arm rather than on the proxiesimal long arm of chromosome No. 3.
Abstract: Chromosome analysing using quinacrine fluorescence was performed on 930 consecutive newborn infants. The total incidence of major chromosome aberrations including numerical changes of the sex chromosomes, and structural changes of autosomes, was 0.54%. Incidences of XYY (0.4%) and XXY (0.2%) were relatively higher as compared to other studies. About 0.75% of the newborn infants were found to have a variable bright fluorescent band located on the proximal area of the short arm (p11) rather than on the proximal long arm (q11) of chromosome No. 3. Attempts were also made to record the variable fluorescent regions on 7 autosomes and the Y chromosome.
TL;DR: A comparison between spontaneous breaks, X-ray induced breaks, breaks in Fanconi's anemia and in congenital rearrangements, show very significant differences.
Abstract: Breakpoint distribution was studied from cultured lymphocytes on 7653 metaphases from 524 subjects whose karyotypes were normal. The mean break rate was 5% in both sexes. The frequency increased significantly after 40 years and varied during the year. The location of the breaks was very different from the expected random distribution. The break frequency for each chromosome was different according to the type of break (chromatid, simple chromosomal and chromosomal involving rearrangements). The location of the breaks was also studied according to the type of band and with respect to the centromere. A comparison between spontaneous breaks, X-ray induced breaks, breaks in Fanconi's anemia and in congenital rearrangements, show very significant differences.
TL;DR: A rapid electrophoretic procedure is described for detecting the human red cell glyoxalase I variants on cellulose acetate gel on which the sites of enzymed activity are visualized as purple bands against white background.
Abstract: A rapid electrophoretic procedure is described for detecting the human red cell glyoxalase I variants (GLO 1, GLO 2-1, and GLO 2) on cellulose acetate gel (cellogel) on which the sites of enzymed activity are visualized as purple bands against white background. The frequency of GLO1 gene in a Dutch population living in and around Leiden was found to be 0.4544.
TL;DR: The authors have plotted on a world map all available data on the frequency of the allele Gc2, and compared the distribution with that of sunlight, and with some exceptions high frequencies of Gc1 correspond to low levels of sunlight and vice versa.
Abstract: Following the discovery by Daiger et al. (1975) that the Gc proteins of human plasma act as the carriers of vitamin D, the authors have plotted on a world map all available data on the frequency of the allele Gc2, and compared the distribution with that of sunlight. With some exceptions high frequencies of Gc2 correspond to low levels of sunlight and vice versa. Similar comparisons within Ireland show no such relation. The results are discussed in relation to natural selection and the incidence of rickets, due to vitamin D deficiency.
TL;DR: Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small Area of the metaphase spread, III) mitotic figures with damage on all chromosomes.
Abstract: Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small area of the metaphase spread, III) mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus.
TL;DR: SOD-A activity was measured by the polarographic method of catalytic currents in 30 subjects 10–24 years of age with a karyotype 47, +21, and 30 age matched normal subjects to confirm that this ratio does not differ significantly from the ratios expected in the case of a simple gene dosage effect.
Abstract: SOD-A activity was measured by the polarographic method of catalytic currents in 30 subjects 10–24 years of age with a karyotype 47, +21, and 30 age matched normal subjects. The ratio of the average amount of SOD-A in 21-trisomic cells to the average amount in normal cells is 1.4495. Statistical analysis confirms that this ratio does not differ significantly from the ratio 1.5 expected in the case of a simple gene dosage effect.
TL;DR: The DNA synthesis pattern and the distribution of mitotic indices indicate a higher yield of asynchrony in Eagle's MEM as compared with Ham's F-10 cultures.
Abstract: In human leukocyte cultures set up with Eagle's MEM and stimulated with Difco's PHA M, DNA synthesis and mitotic indices were analyzed by means of 3(H)-thymidine autoradiography and cell counting from 23 up to 52 h after culture initiation. Considerable amounts of DNA synthesis and mitoses were found in this time span. This resembles the results found with Ham's F-10 medium. However, the DNA synthesis pattern and the distribution of mitotic indices a higher yield of asynchrony in Eagle's MEM as compared with Ham's F-10 cultures. Proportions of first, second, and third mitoses at 72 h culture time were determined with different methods.
TL;DR: The ability to recognize small spots of coloured light in parafoveal regions of the retina was investigated in women heterozygous for protanopia, deuteranopia and normal subjects, finding the ability to differentiate colours varied from point to point within the retina.
Abstract: Bei 2 Konduktorinnen fur Protanopie, bei 2 Konduktorinnen fur Deuteranopie und bei 1 Konduktorin fur Deuteranomalie wurde im Vergleich zu 3 normal Farbentuchtigen die Erkennungsfahigkeit fur kleine farbige Punkte in parazentralen Netzhautregionen untersucht. Hierbei zeigten sich bei den heterozygoten Ubertragerinnen fur angeborene Farbensinnstorungen dicht nebeneinanderliegende Stellen guter und schlechter Erkennbarkeit, wahrend bei den homozygot normalen Farbentuchtigen die Erkennbarkeit farbiger Reizpunkte bis zu 8° Abstand vom Fixierpunkt gleichmasig gut war. Die Befunde lassen sich am besten mit einer Mosaikstruktur der Netzhaut bei den Heterozygoten erklaren, wobei anscheinend Areale farbentuchtiger und farbenuntuchtiger Zellpopulationen miteinander abwechseln.
TL;DR: Fluorescence markers were studied in 40 patients with Down's syndrome and their parents and in 11 cases maternal and in 5 cases paternal non-disjunction could be shown.
Abstract: Fluorescence markers were studied in 40 patients with Down's syndrome and their parents. In 11 cases maternal and in 5 cases paternal non-disjunction could be shown. The disjunctional event occurred in the first meiotic division in 5 maternal and in 2 paternal cases. A second division failure was found in 4 maternal and 2 paternal cases. In 3 cases the failure could either be of first or second meiotic division origin.
TL;DR: The first child of a mother with a balanced translocation revealed a trisomy for the distal third of 13q and presented also male pseudohermaphroditism and trigonocephaly.
Abstract: The first child of a mother with a balanced translocation (9;13) revealed a trisomy for the distal third of 13q. Clinical signs were microcephaly, hemangiomata, long incurved eyelashes, strabismus, enlarged bridge of the nose, abnormally long philtrum, high-arched palate, low set ears, hexadactyly of the four extremities, umbilical and inguinal hernias, neonatal respiratory distress, psychomotor and growth retardation. The proband presented also male pseudohermaphroditism and trigonocephaly. This last trait is the object of a discussion in which cases of partial trisomy 13q cited in the literature are considered for study of the incidence of this dyscephaly in this particular syndrome.
TL;DR: In situ hybridization using tritium-labeled 28S and 18S RNA shows that in the interphase nucleus the acrocentric short arms, carriers of ribosomal cistrons, are associated with the nucleolus, confirming that theucleolus constitutes one of the orientation points determining the relative localization of chromosomes in theinterphase nucleus.
Abstract: Use of specific stains permits analysis of the frequency of nucleolus-associated heterochromatin in chromosomes 1 and 9 from human fibroblasts. In 81% of interphase nuclei the heterochromatic segment of both No. 1 chromosomes is associated with the nucleolus, while in 19% only one heterochromatic segment shows such an association with the other occupying a random position in the nucleoplasm. The nucleolar association of chromosome 9 heterochromatin is less constant: in 42.3% of the nuclei both segments are associated with the nucleolus, in 39% of the nuclei only one heterochromatic segment presents such an association, and in 18.7% neither of the two heterochromatic segments is in nucleolar association. In 6% of the cells, one or two chromosome 9 heterochromatic segments are in contact with the nuclear membrane.
TL;DR: This paper showed that pyruvate kinase from all the other tissues on the other hand were inhibited by anti-M2 and not at all by anti L serum, and the latter group represent the M type pyruve kinase isozymes.
Abstract: Anti human M2 type and anti human L type pyruvate kinase sera allowed us to distinguish two groups of pyruvate kinase in man. Erythrocyte and liver (L type) enzymes on the one hand were inhibited by anti L and not at all by anti M2 serum; pyruvate kinase from all the other tissues on the other hand were inhibited by anti M2 and not at all by anti L serum. This latter group represent the M type pyruvate kinase isozymes.
TL;DR: From the patient's clinical examination and from review of 13 similar cases reported in the literature, the following phenotype emerged: constant features were psychomotor retardation, muscle hypotonia at birth, undescended testes in all males and abnormal auricles, typically with a prominent antitragus.
Abstract: This communication contributes an additional case of partial trisomy for the long arm of chromosome 4[46,XX,t(X;4)(Q27;Q25)]. Three generations of the patient's family were karyotyped and her mother and brother were found to be balanced translocation carriers. From the patient's clinical examination and from review of 13 similar cases reported in the literature, the following phenotype emerged: constant features were psychomotor retardation, muscle hypotonia at birth, undescended testes in all males and abnormal auricles, typically with a prominent antitragus. Anomalies of kidneys and other structures of the urinary system were present consistently as probably the most characteristic feature of the syndrome. Over 200 structural anomalies of other systems were reported, many of the common to other autosomal chromosomal syndromes.
TL;DR: Localization of chromosome breaks in human chromosomes was analyzed in 264 peripheral lymphocyte cultures and found that three hundred and sixty-nine chromosome breaks could be exactly localized to a chromosome band or region of the Paris Conference nomenclature.
Abstract: Localization of chromosome breaks in human chromosomes was analyzed in 264 peripheral lymphocyte cultures. Three hundred and sixty-nine chromosome breaks could be exactly localized to a chromosome band or region of the Paris Conference nomenclature. The distribution of breaks in the chromosome regions was found to be nonrandom. Chromosome 3 alone had 23% of the breaks and region 3p2 had 13% of the total breaks. Some other chromosome regions, such as 5p1, 9q1, 14q2, and 16q2 also displayed clustering of breaks. Sex chromosomes had less breaks than expected. Spontaneous chromosome breaks were almost exclusively located in the lightly stained G bands.
TL;DR: Data were presented to indicate that the hereditary form of retinoblastoma onset tends to be later in unilateral than in bilateral affection, though in the non-hereditary form onset will be further delayed.
Abstract: Analyses of family data published in Japan concerning 29 kindreds with 2 or more cases of retinoblastoma revealed that, in the children who received the gene from a carrier parent, both penetrance and expressivity increase with increasing degree of expressivity in the parent. The estimate for the average degree of penetrance varies from 0.7 to 0.9, depending upon the method employed. The value will be increased with increasing number of survivors of hereditary retinoblastoma. Data were presented to indicate that the hereditary form of retinoblastoma onset tends to be later in unilateral than in bilateral affection, though in the non-hereditary form onset will be further delayed. No effect of birth order was detected. It was suggested that suppressor genes at other loci play a significant role in manifestation of the major dominant gene for retinoblastoma. Implications of these findings were discussed.
TL;DR: Eighteen of 38 examined families with children with Down's syndrome showed polymorphisms of chromosome 21 elucidating the origin of the extra chromosome 21, and errors occurred both in the first and the second meiotic division.
Abstract: Eighteen of 38 examined families with children with Down's syndrome showed polymorphisms of chromosome 21 elucidating the origin of the extra chromosome 21. Maternal origin was found in 10 cases and paternal origin in 8 cases. In both sexes errors occurred both in the first and in the second meiotic division.
TL;DR: The final result of cytogenetic investigation of 607 premature infants was that chromosome anomalies were found among 2.5 times as much as in the general newborn population, and the proof of the fact, that other types of anomalies, found in newborn populations lead to earlier lethality.
Abstract: 363 samples of different tissues were taken for cultivation from 118 antepartum deaths, 85 intrapartum deaths and 112 newborn dying during the first days after delivery. Successful growth of culture was noticed in 48.2% (15.4%) of antepartum deaths; 71.8% of intrapartum deaths and 68.1% of newborn dying during the first days of life. Among the 22 antepartum deaths 3 (13.6%) infants were found to have anomalies of karyotype; among 61 intrapartum deaths 3 (4.9%) infants were found to have karyotype anomalies; and among 92 early neonatal deaths 6 ones (6.5%) had karyotype anomalies. The total frequency of chromosome anomalies among the infants dying during the perinatal period was 6.9%. The final result of cytogenetic investigation of 607 premature infants was that chromosome anomalies were found among 2.5%, that is 3.5 times as much, as in the general newborn population. Among the types of chromosome anomalies the main defects were anomalies in the system of sex chromosomes and trisomy-21, and that is the proof of the fact, that other types of anomalies, found in newborn populations lead to earlier lethality.