Karin E. Buckton

Forty four probands with an additional “marker” chromosome

SummaryInformation is presented which has been obtained from an exhaustive examination of 44 probands with a supernumerary marker chromosome (mar) and their families. The data include the derivation of the mar, frequency in various populations, inheritance and possible effect on fertility, congenital abnormality, and mental ability. The practical problems in assessing the risk of abnormality in a foetus discovered during prenatal diagnosis to be carrying a mar, are discussed.

Radiation-induced chromosome aberrations in nuclear-dockyard workers.

The incidence of chromosome aberrations in peripheral blood lymphocytes of 197 dockyard workers has been followed over a 10-yr period. These workers were exposed to mixed neutronγ radiation during the refuelling of nuclear reactors, but most exposures were below the internationally accepted maximum permissible level of 5 rem per yr. There was a significant increase in chromosome damage with increasing exposure, aberration frequency was a linear function of dose and was influenced by age and time of blood sampling after exposure.

Lymphocyte survival in men treated with x-rays for ankylosing spondylitis.

Lymphocytes with radiation-induced chromosome aberrations, examined in patients treated with X-rays for ankylosing spondylitis, are estimated to have a mean life span of about 1,600 days.

Cytological mapping of human chromosomes: results obtained with Quinacrine fluorescence and the Acetic-Saline-Giemsa techniques

The similarities and differences between the banding patterns obtained in human chromosomes with the Quinacrine fluorescence and the Acetic-Saline-Giemsa (ASG) techniques are described. The use of these techniques to identify each chromosome pair in the human karyotype is discussed, as also is the use of the methods to identify aberrant chromosomes and to map points of exchange in translocations and inversions. A number of examples are used to illustrate the resolution permitted by these new methods. Seven polymorphic regions on normal chromosomes are described, which include four identified by fluorescence on chromosomes 3,4, 13, and 22. The secondary constrictions on chromosomes 1, 9, and 16, which had previously been observed in conventionally stained preparations from favourable material, are particularly clear in all cells treated with the Giemsa techniques. The new methods make it possible to detect small differences in size between the heterochromatic blocks at these regions in homologous chromosomes. The benefit to human genetics of studying the familial segregation of both structurally rearranged and normal, but polymorphic chromosomes, where the chromosomes or parts of chromosomes can be unambiguously identified is stressed.

Identification with G and R banding of the position of breakage points induced in human chromosomes by in vitro x-irradiation.

The aberrations seen in chromosomes of human peripheral-blood lymphocytes, X-irradiated in vitro, have been analysed in three types of preparations, treated to give G-banding; R-banding; and G-banding followed by R-banding on the same cells. The data from cells subjected to both banding techniques reveals that 30 per cent of the sites of chromosome breakage are situated at he interfaces between dark- and - light-stained bands. The results of all the analyses show that approximately 30 per cent of all breaks were located in either the telomere (19-5 per cent) or centromere (11-3 per cent) regions. Chromosomes rich in R-band material were not preferentially damaged, but chromosomes 12, 15, and particularly 17, were involved in aberrations more frequently than would be expected on the basis of their length. No breaks were found on the Y chromosome in the 114 male cells analysed, but the X did not appear to be spared from damage either in the male cells analysed, but the X did not appear to be spared from damage either in the male cell or the 136 female cells analysed. G and/or R-banding enables a much more accurate analysis of aberrations than can be obtained from the use of conventional staining techniques, and with these methods, it is shown that the numbers of induced asymmetrical and symmetrical exchanges are similar.

An Analysis of the Break Points of Structural Rearrangements in Man

The distribution of the points of breakage and reunion of a series of 58 Robertsonian translocations, 53 reciprocal translocations, and 10 inversions is described. An excess of 13/14 and 14/21 rearrangements was found among the Robertsonian translocations, this excess being independent of the method of ascertainment of the proband. The distribution of break points between chromosome arms in the reciprocal translocations, with the possible exception of the long arms of chromosome 11, was no different from that expected on the basis of their relative lengths. However, within arms there appeared to be an excess of breaks in the terminal regions, an excess of terminal/centromeric translocations where ascertainment was through a balanced carrier and a possible excess of terminal/median translocations where ascertainment was through an unbalanced carrier. Nine inversions were analysed and three of these involved identical break points on chromosome 8. Possible reasons for the apparent non-randomness of points of breakage and exchange are discussed and it is concluded that the techniques of preparation, methods of observations, and methods of ascertainment all affect the distribution of observed points of breakage and exchange and must therefore be taken into cognizance in any study of chromosome rearrangements in man.

A G‐band study of chromosomes in liveborn infants

The results of a chromosome survey of 3993 liveborn infants, the majority of which have been studied using G-banding, are reported. The frequency of all types of chromosome abnormalities detected was similar to that found in previous newborn surveys, which were carried out on different socio-economic structure, but the incidence of aneuploid chromosome abnormalities was comparable in the two localities.

Four patients with trisomy 8 identified by the fluorescence and Giemsa banding techniques.

The C group chromosomes in man cannot be distinguished solely on morphological grounds, thus, the nature of an extra C chromosome remains unknown unless it is an X chromosome, which can be identified by its late DNA-replication pattern. Extra autosomes belonging to the C group have been observed with or without mosaicism in a wide variety of blood disorders (cf, de la Chapelle et al, 1970; Hellstrom et al, 1971), in spontaneous abortions (Boue and Boue, 1969), in malformed and/or mentally retarded subjects (Pfeiffer, Schellong, and Kosenow, 1962; El-Alfi, Powell, and Biesele, 1963; Stalder, Buhler, and Weber, 1963; Stolte, Evers, and Blankenborg, 1964; Wolf and Reinwein, 1965; Jalbert et al, 1966; Kerr and Rashad, 1966; Schutt, 1966; Juberg, Gilbert, and Salisbury, 1970), in one female with primary amenorrhoea (Jacobs et al, 1961), and in one apparently healthy female who gave birth to malformed children (Smith, 1964). This great variation in the clinical picture speaks in favour of different C autosomes having been involved, an hypothesis which has-so far-been impossible to test. The fluorescence and Giemsa banding techniques offer a new possibility to study this problem, and in the present work we describe 4 patients with an extra C chromosome all identified

An inhertited X-autosome translocation in man

The inability to distinguish the human X chromosome from the autosomes in the C group in conventionally stained mitotic preparations has resulted in several translocations involving a C group chromosome being described as possible X-autosome translocations (Mann et al. 1965; Neuhauser & Bach, 1966; Thorburn, Martin & Pathak, 1970). The suggestion that the X chromosome is involved in the rearrangement has usually been made because the carrier has some abnormality of the primary or secondary sex characters. In addition, two X-autosome translocations have been reported in man where the identity of the X chromosome was established using autoradiography (Mukherjee & Burdette, 1966; German, 1967). In these latter two cases the X chromosome involved in the rearrangement was always found to be the one which completed DNA replication late in the S-period. However, autoradiographic techniques can only identify a structural abnormality involving the X chromosome where more than one X chroinosome is present and, furthermore, only when the structurally abnormal X is late replicating in all, or a significant proportion of, the cells examined. Recently Caspersson and his colleagues have demonstrated that it is possible to identify all the human chromosomes by utilizing the ability of quinacrine mustard to bind with specific regions of the chromosomes, so that when viewed under U.V. illumination each chromosome pair has a characteristic fluorometric profile (Caspersson, Zech & Johansson, 1970). It was shown that a similar discrimination can be made on the basis of differences in fluorescing banding patterns when chromosomes are stained with quinacrine dihydrochloride (O’Riordan et al. 1971). Using this technique we have demonstrated that a reciprocal translocation between a C group and a D group chromosome is a t ( X p ; 14g+ ). Our findings in the family in which this X-autosome rearrangement is segregating form the basis of the present report.

Assignment of the human locus determining phosphoglycolate phosphatase (PGP) to chromosome 16

The segregation of human phosphoglycolate phosphatase has been studied in 52 independent human-rodent hybrids and 69 subclones. The results suggest that human PGP is on chromosome 16. Family data suggest that PGP is not close to 16qh or alpha Hp. The most likely regional assignment for PGP would appear to be 16p13 or 16p12, but a site on 16q cannot be entirely excluded. New data on 16qh and alpha Hp suggest that the male recombination fraction between these loci is about 0.2.