Showing papers in "Human Genetics in 1972"

Cytological and cytogenetical studies on brain tumors. 4. Identification of the missing G chromosome in human meningiomas as no. 22 by fluorescence technique.

Abstract: Among 70 human meningiomas cytogenetically investigated by us up till now, only 4 tumors showed a hyperdiploidy. 2 of them had a uniform stemline with 47 chromosomes (47,XX,G+ and 47, XY, C(?E)+); the other 2 meningiomas had a stemline with a modal number of 53 (55) chromosomes.

The spontaneous azaguanine-resistant mutants of diploid human fibroblasts.

Abstract: The range of incidences of azaguanine-resistant colonies in cultures of fibroblasts from 16 unrelated humans was 0.4×10-6 to 19×10-6 and the mean value was 4.1×10-6. A fluctuation test showed that most or all of the mutant colonies derived from mutations that occurred during in vitro proliferation of the fibroblasts and before exposure to azaguanine. The estimated rate of spontaneous mutation was 0.45×10-6 to 1.8×10-6 per cell generation. At least ten independent mutants, comprising two general classes, were studied. Class I mutants were a minority and resembled cells from boys having the Lesch-Nyhan syndrome: they had very little HG-PRT activity, showed maximum resistance to azaguanine and could not utilize hypoxanthine for growth. At least 90% of the mutants were in Class II: their apparent HG-PRT activities ranged between normal and Lesch-Nyhan amounts, they were partially sensitive to azaguanine and they could utilize hypoxanthine. Some Class II mutants resembled cells cultured from a family having an X-chromosomal mutant gene that does not cause the Lesch-Nyhan syndrome but does confer resistance to azaguanine, although the quantity of HG-PRT activity is apparently normal and hypoxanthine can be utilized. Electrophoretic differences between the HG-PRT activities of normal and mutant strains were not detected but other qualitative alterations were observed in some mutants.

Dicentric and monocentric Robertsonian translocations in man.

Abstract: 5 balanced Robertsonian translocations in man were identified by fluorescence studies. Orcein staining showed two distinct centromeres in 4 of these cases (tdic(13;13), tdic(13;14), tdic(15;21), tdic(21;22)) indicating breaks in the short arms of the involved chromosomes. The dicentric translocation chromosomes were rather stable but monocentrics were noticed in each case. Fluorescence- and measurement studies seemed to indicate that an invisible centromere and part of the short arms were present in these monocentric chromosomes. One case, t(14q21q), was monocentric in all metaphase plates but measurement studies were very suggestive of a visible 21 centromere and incorporation of the invisible 14 centromere (and short arm material) in the long arm of the translocated 14 chromosome, indicating that this translocation originally might have been a real dicentric. Heterochromatin staining was carried out in all cases. The tdic(15;21) showed 6 heterochromatin blocks; 2 of these blocks were probably satellites from chromosome No. 21, visible too in fluorescence. The 4 other translocations showed 4 separated blocks. No differences were observed between monocentrics and dicentrics supporting the theory of a preserved, but invisible centromere in monocentrics.

Identification of two Robertsonian translocations with a Giemsa banding technique.

Abstract: Using a trypsin banding technique a D/D and a G/G translocation were identified as D-13/14 and G-21/22.

On the number of ribosomal RNA genes in man.

Abstract: The saturation plateau of the high molecular weight species of ribosomal RNA was determined for DNA of human liver from a female and a male person with normal karyotypes. The amount of DNA annealing with (18s+28s) RNA of HeLa cells is equivalent to 443±21 or 416±19 copies of the corresponding gene loci, depending on the set of molecular weights of 18s and 28s RNA used in the calculation.

Identity of the abnormal F-group chromosome associated with polycythaemia vera.

Abstract: A technique for the identification of individual chromosomes has been applied to bone marrow cells from 4 patients with polycythaemia vera. These patients were already known to have the abnormal F-group chromosomes which occur in about 20% of cases of this disease. In each individual the particular chromosome involved was found to be a number 20, from which some material had been deleted, probably from the long arm.

Neuer Typ einer recessiv X-chromosomal vererbten Muskeldystrophie: Scapulo-humero-distale Muskeldystrophie mit frühzeitigen Kontrakturen und Herzrhythmusstörungen

Abstract: Es wird uber eine neue Form einer recessiv X-chromosomal vererbten progressiven Muskeldystrophie berichtet. Dieses Krankheitsbild wurde bei 17 Kranken in 3 Generationen einer in Niederbayern ansassigen Sippe beobachtet. Der Erkrankungsbeginn lag bei der Mehrzahl der Patienten in der ersten Lebensdekade. Ein Fruhsymptom waren fibrotisch bedingte Kontrakturen insbesondere des M. gastrocnemius, der ischioeruralen und paravertebralen Muskeln sowie des M.biceps brachii. Als Folge dieser Veranderungen kam es zu fruhzeitigen Bewegungseinschrankungen in den entsprechenden Gelenken. Pseudohypertrophien wurden in keinem Stadium beobachtet. Bei relativ langsamer Progredienz zeigten die auftretenden Paresen und Atrophien eine scapulo-humero-distale Verteilung mit peripher betonten Extensorschwachen. Gehunfahigkeit trat nicht vor der vierten Lebensdekade ein. Die Fertilitat war ungestort. Das Todesalter der 9 bisher verstorbenen Kranken lag zwischen 37 und 59 Jahren; alle 9 Patienten verstarben plotzlich, wahrscheinlich als Folge einer schon vorher bestehenden Herzrhythmusstorung. Bei 5 Kranken wurden im Elektrokardiogramm Rhythmusstorungen in Form eines totalen AV-Blockes mit Reizbildung im AV-Knoten oder in tertiaren Zentren nachgewiesen. Die elektromyographischen und histologisch-enzymhistochemischen Untersuchungen zeigten einen myopathischen Krankheitsprozes an. Die motorische und sensible Nervenleitgeschwindigkeit war normal. Die Aktivitat der Serum-CPK war bei allen jungen Patienten leicht bis stark erhoht, bei den alteren Patienten war die Aktivitat normal. Sichere und mogliche Konduktorinnen zeigten weder klinische Symptome noch Erhohungen der Serum-CPK. Die klinische Symptomatik und das Verhalten der Serum-CPK erlauben eine sichere differentialdiagnostische Abgrenzung von anderen Myopathien, insbesondere auch von den recessiv X-chromosomal erblichen Muskeldystrophien Typ Duchenne und Typ Becker-Kiener.

Cat-eye syndrome, a partial trisomy 22.

Abstract: A family is presented in which a phenotypically normal mother and her healthy daughter both had abnormal children with a small supernumerary chromosome. Both had clinical symptoms suggestive of cat-eye syndrome. In both women 1 G-chromosome was found to be replaced by a small submetacentric satellited chromosome. Its fluorescence pattern was compatible with that of a chromosome 22, and so was the fluorescence pattern of the supernumerary chromosome in one of the phenotypically abnormal children. Since complete monosomy G in addition to partial autosomal trisomy would not be compatible with clinical “normality” the respective karyotypes must be interpreted as a small deletion of a chromosome 22 in the healthy mother and daughter and a partial trisomy 22 in their abnormal children. Therefore it can be concluded that a deletion of a chromosome 22 is compatible with a normal phenotype and that the cat-eye syndrome results, at least in this family, from a partial trisomy 22.

Ultrastructural distinction of autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis.

Abstract: In autosomal dominant ichthyosis vularis ultrastructural studies have revealed a severe disturbance of keratohyalin synthesis by which this entity may clearly be distinguished from X-linked ichthyosis.

Lipoproteins in LCAT-deficiency.

Abstract: Purified lipoproteins from 2 brothers and 1 unrelated male patient with lecithincholesterol-acyltransferase deficiency were investigated. All 3 patients exhibited the changes in properties of high-density-lipoproteins that have been described in familial lecithin-cholesterol-acyltransferase deficiency. In all 3 patients we also observed a low-density-lipoprotein indistinguishable from the LP-X protein characteristic of obstructive jaundice. Criteria of comparison were electrophoretic mobility, flotation behaviour, immunological properties, appearance in electron microscopy and lipid composition. In 2 of the patients there was no sign of biliary obstruction (brothers G. M. and P. M.); it, therefore, is assumed that they suffer from the familial form of LCAT-deficiency, whereas the third patient (V.M.) exhibited signs of intrahepatic obstruction. From this as well as from further comparative studies of patients with biliary obstruction it is concluded that there exists a primary and a secondary form of LCAT-deficiency, both of which may result in the same changes of lipoprotein patterns. In the present study the disease was found to be characterized mainly by 1. two different abnormal lipoproteins, one of low density containing apoprotein C and albumin, and the other of high density containing apoprotein A, both of which demonstrate a disk-like appearance with a tendency to rouleaux formation, when examined by electron microscopy, and 2. by a protein with immunological properties of apoprotein A in fractions DHL3 and ϱ>1.21 g/ml, that does not stain with lipid dyes.

A rapid banding technique for routine use in human and comparative cytogenetics.

Abstract: A simple combined enzyme-stain technique is described which gives within 20 min clear banding patterns in mammalian chromosomes.

Chromosomal aneuploidy in human spermatozoa

Abstract: Recently developed staining techniques have made it possible to recognize the Y and number 9 chromosome in human spermatozoan heads. Thus, the frequency of numerical aberrations involving these two chromsomes has become amenable to investigation in sperm. Y Chromosome. I t is well established that the distal portion of the human Y chromosome at metaphase fluoresces more intensely than the rest of the karyotype after quinacrine staining (Caspersson et al., 1970). By this property the presence of the Y chromosome can also be demonstrated in the interphase of somatic cells (Pearson et al., 1970) at meiosis (Pearson and Bobrow, 1970) and in mature spermatozoa (Barlow and Vosa, 1970). The objective of the present study (Pawlowitzki and Pearson, 1971) was to count spermatozoa with two Y bodies in a series of fertile men in order to estimate the frequency of meiotic errors involving the Y chromosome in the normal male population. A total of 10.692 spermatozoa obtained from ejaculates of 12 normal fertile healthy males were examined. 5 of these (individuals No. 7 t2 , Table t) w e r e donors of a sperm bank 1, their semen had been stored for periods up to several months in liquid nitrogen at temperatures of ~ 190°C before investigation. The technique of the fluorescent examination (Pearson and Bobrow, 1970) and the criteria of counting sperm and fluorescent bodies (Pawlowitzki, Habflitationsschrift, 1971) were described elsewere in detail. The results are shown in the table: 54.6% of the examined spermatozoa had no fluorescent body, presumably being X bearing sperm. In 43.9% a single fluorescent body was seen, which are considered to be Y bearing sperm. 1.3% had 2 fluorescent bodies and therefore are believed to contain a supernumerary Y chromosome. Giant forms with 2 fluorescent bodies (0.2%) were counted separately, since these may be polyploid (Sumner, 1971; Pawlowitzki and Bosse, 1972). The contribution of polyploidy to sperm with doubled Y bodies appears to be about 1 in 7. Our results on the frequency of YY gametes in healthy fertile men are in good agreement with the results of other studies: Pearson and Bobrow (1970) found 1.4% spermatids with 2 fluorescent bodies each in testicular tissue of 3 normal

Differential cell division in human X chromosome mosaics.

Abstract: Fibroblasts were grown from skin explants of 3 human females who are sex chromosome mosaics. The 3 cultures had the following chromosome complements: 45,X/46,XX, 45,X/46,XXqi and 45,X/47,XXX. Using thymidine labelling and Colcemid accumulation of metaphases it was found that in all 3 mosaic cultures the 45,X cells had a faster cell cycle than the second cell population. The difference in cell cycle duration was attributed to the longer G1 phase in the cells with 2 or 3 X chromosomes. The 2 populations of cells in the mosaic only differ in the number of heterochromatic X chromosomes and it is argued that heterochromatin has a retardative effect on cell division.

Follow-up of a family group suffering from ichthyosis hystrix type Curth-Macklin.

Abstract: A family examined by Curth and Macklin in 1952 and found to suffer from generalized or localized forms of ichthyosis, was reexamined in 1970. The concept that the disorder had been conditioned by a dominant gene which manifested itself with varying degrees of severity in the various family members, seemed proved again.

Neues zur Genetik und Klassifikation der Muskeldystrophien

Abstract: A survey of the genetics of muscular dystrophies (without congenital, ocular and distal myopathies) is given, resulting in the following preliminary classification: I. X-linked muscular dystrophies 1. Infantile or severe type (Duchenne) 2. Juvenile or benign type (Becker-Kiener) 3. Benign type with early contractions (Cestan-Lejonne and Emery-Dreifuss) 4. Late type (Heyck-Laudahn)? 5. Hemizygous lethal type (Henson-Muller-De Myer)? II. Dominant autosomal muscular dystrophy 6. Facio-scapulo-humeral type (Erb-Landouzy-Dejerine) III. Recessive autosomal muscular dystrophies 1. Infantile type 2. Juvenile type 3. Adult type? 4. Shoulder-girdle type?

Partial monosomies 18. Review of cytogenetical and phenotypical variants.

Abstract: This paper contains a survey of clinical and chromosome data of about 170 patients with partial monosomies 18 (18p-; 18q-; 18r). Cases with karyotype (18q-) show a very distinct malformation syndrome. The symptoms of (18r) cases are in-between those of (18p-) and (18q-).

Studies on the Lp(a)-lipoprotein of human serum. IV. The disaggregation of the Lp(a)-lipoprotein.

Abstract: Lp(a)-lipoprotein of human serum, when isolated by ultracentrifugation and gelfiltration on Sepharose 4 B, may disaggregate into several components either spontaneously or by mild treatment with detergents:

Autosomal dominante Vererbung von Gaumenspalte und Synechien zwischen Gaumen und Mundboden oder Zunge

Abstract: Eine bisher nicht beschriebene Form der Kombination einer Gaumenspllte mit zahlreichen, meist symmetrischen, strangformigen Verwachsungen zwischen den Randern der Spalte und seitlichen Partien der Zunge sowie dem Mundboden in der Gegend der Glandula sublingualis wurde bei 5 (bei Einschlus eines Mannes mit inkompletter Auspragung, 6) Mitgliedern einer Familie beobachtet. Zusatzliche Kennzeichen waren eine masige Hypoplasie des Unterkiefers und der Zunge sowie eine relativ kurze Oberlippe. Es bestanden keine weiteren begleitmisbildungen. Die Verteilung der Probanden im Stammbaum spricht fur autosomaldominanten Erbgang. Die Anomalie ist eindeutig gegenuber dem Ankyloglosson superius-Syndrom und der konnatalen Syngnathie abzugrenzen. Als englische Kurzbezeichnung wird der Terminus “Cleft Palate Lateral Synechia-Syndrome” vorgeschlagen.

Gene activation during early development of mammals.

Abstract: The preimplantative stage of development has as yet not been studied extensively; most data were derived from the mouse and the rabbit. In this article, the results on macromolecular synthesis during this period of development are summarized. In the beginning, the embryonic genome is apparently genetically inactive; early development is governed by maternal storage products transmitted through the egg cytoplasm. Activation of embryonic genes occurs step-wise, with the protein synthesizing apparatus being produced first. Synthesis of individual proteins (enzymes) coded for by embryonic genes apparently in general does not start before the middle blastocyst stage, shortly before implantation. It is discussed whether cytoplasmic storage products take part in gene activation during this period.

Nucleoli and Chromosomes: Their Relationships during the Meiotic Prophase of the Human Fetal Oocyte

Abstract: The number of nucleoli and the relations between them and chromosomes in the human fetal oocyte have been investigated in this study. The differences existing between first oocytes and spermatocytes have been emphasized. These differences concern essentially the number of nucleoli, the stage during which they appear and the quantity of heterochromatin associated with the nucleoli. The latter appear very early in the oocyte: they are already present at the beginning of the preleptotene stage. This stage is characterized by the processes of spiralization and despiralization, heretofore not described. The first prophase is characterized by the presence of abundant nucleolar material, especially in the diplotene stage. This abundance is certainly in relation with the active protein synthesis which characterizes the growth of the oocyte. As in the spermatocyte of the pachytene stage, the majority of nucleolar chromosomes, in the oocyte, are acrocentric. But in the latter, the quantity of heterochromatin associated with the nucleolus greatly exceeds the quantity present in the nucleolar organizers of acrocentric chromosomes, particularly during the leptotene stage. This supports the opinion that there are multiple sites for the synthesis of the various nucleolar componnents. Also discussed are the roles of heterochromatin and nucleolar organizers in nucleogenesis.

C 11/D 13-translocation in four generations

Abstract: In a pedigree with familial C 11/D 13-translocation the chromosomes of 18 persons in 4 generations were analyzed. 8 of them had a normal karyotype, in 8 cases a balanced translocation was found. Totally 7 children with different multiple malformations were observed, 5 of whom had already died at the time of investigation. The other 2 showed an unbalanced translocation C 11/D 13 with partial trisomy for the long arm of chromosome C 11. These children showed the same syndrome (mental retardation, low birth weight, cutis laxa, hypertelorism, broad flat nose, micrognathia with retracted lower lip, heart malformation, ridge dysplasia of dermatoglyphics).

Chromosome studies in persons treated with anticonvulsant drugs

Abstract: Bei 32 mit Anticonvulsiva behandelten Epileptikerinnen und ihren in der Schwangerschaft diesen Medikamenten ausgesetzten Kindern im Alter von 0–3 Jahren lag die Rate struktureller Chromosomenaberrationen signifikant (p<0,001) uber den Werten der unbehandelten, gesunden Vergleichspersonen. Da in den meisten Fallen verschiedene Anticonvulsiva gleichzeitig eingenommen worden waren, konnte nicht entschieden werden, ob Unterschiede in der chromosomenaberrationsauslosenden Wirkung zwischen den einzelnen Anticonvulsiva-Praparate-Gruppen bestehen. Zwischen den Werten der Mutter und der jeweiligen Kinder bestand eine signifikante Korrelation. Hinweise auf eine teratogene Wirkung der untersuchten Anticonvulsiva-Praparate ergaben sich nicht. Die Haufigkeit von Aborten, Totgeburten und misgebildeten Kindern war in der vorliegenden Untersuchung nicht erhoht.

Quinacrine mustard fluorescence of a second Y chromosome in a Y-autosomal translocation

Abstract: Screening buccal smears from 97 prisoners by the quinacrine mustard technique revealed one XYY-individual and one Y-autosomal translocation of a second Y chromosome with a 46,XY, D-,t (?15q;Yq)+ karyotype. The translocation chromosome could be identified by its intense fluorescence of the short arm in all 75 metaphases examined.

The effect of maternal age on the incidence of Down's syndrome.

Abstract: An effect of increasing maternal age has been demonstrated on the frequencies of some types of human chromosomal abnormalities. I t seems to be a causal factor in all autosomal tr isomy syndromes (Penrose, 1933 ; Smith et al., 1963 ; Heeht et al., 1963 ; Lenz et al., 1966 ; Hamerton, 1971 b) and also in X X Y Klinefelter's syndrome (Fr~land, 1969). In other human chromosome abnormalities, however, increasing maternal age effects have not been demonstrated, e.g. Tumor ' s syndrome and various translocation syndromes. Down's syndrome is one of the chromosomal diseases where the patients belong to two main groups. The first group consists of patients where maternal age is a fundamental causal factor, while in the second group maternal age seems to have an insignificant effect (Penrose and Smith, 1966). Most of the mongols born to young mothers would belong to the second group and be caused by processes unrelated to maternal age. As ])oven's syndrome is the most common autosomal abnormality, large materials are available to demonstrate different aspects and problems connected with an age-dependent incidence.

Diabetes mellitus in patients with aneuploid chromosome aberrations and in their parents

Abstract: The frequency of chemical diabetes is increased in patients with aneuploid sex chromosome aberrations such as Klinefelter's syndrome and Turner's syndrome, and a high frequency of chemical diabetes has been found in parents of patients with Down's syndrome. Abnormal pattern in plasma insulin and growth hormone during a glucose load has been found in patients with Klinefelter's syndrome and Turner's syndrome.

Partielle Trisomie des kurzen Arms von Chromosom 4 mit Translokation 4p-,18q+ beim Vater

Abstract: Es wird uber einen Knaben mit einem charakteristischen Dysmorphiesyndrom bei partieller Trisomie des kurzen Armes von Chromosom 4 berichtet, der im Alter von 7 Monaten verstarb. Der Patient wies die folgenden Merkmale auf: eigenartiges Gesicht mit Hypertelorismus, enge Lidspalten und an der Basis eingezogene, knollig deformierte Nase, dysmorphe Ohrmuscheln, einseitiges Fehlen der 12. Rippe, Huftgelenksluxation, Deformitat des knochernen Beckens, Hakenfuse mit hypoplastischen Tali und vorspringenden Fersen, Flexionsdeformitat der Finger, Kryptorchismus, Leistenhernie und im Dermatoglyphenbild Haufung von Wirbelmustern auf den Fingerbeeren. Im Karyotyp lag eine Translokation auf den langen Arm eines Chromosoms 18 vor, bei entsprechender reziproker Translokation beim Vater: t(4p-,18q+). Als Nebenbefund fand sich bei Vater und Sohn eine extreme Anisomorphie der Chromosomen 16, bedingt durch die Verlangerung des heterochromatischen, parazentrischen Abschnittes auf dem langen Arm des einen Homologen.

Comments on the determination of isoenzyme polymorphism (ADA, AK, 6-PGD, PGM) by cellulose acetate electrophoresis.

Abstract: The paper highlights certain peculiarities of isoenzyme polymorphism as determined by cellulose acetate electrophoresis, as compared to other supporting media at different pH levels and concentrations of the buffer.