William D. Kaplan

Chromosomal aberrations in man

Summary The following are the most significant points to emerge in summarizing the present status of the field of human cytogenetics. 1. The human chromosome number is 46; a standard system of nomenclature has been established for identification of somatic metaphase chromosomes. Methods, however, are not yet refined enough to detect small changes within individual chromosomes. 2. The sexual dimorphism existing in somatic cells due to the presence of sex chromatin in nuclei of females permits a rapid survey method for detecting discrepancies between phenotypic and genotypic sex. Chromatin positivity or negativity, however, should be correlated with chromosome analyses since only limited deductions concerning the sex chromosome complement can be made from the presence or absence of sex chromatin. 3. The sex chromatin body in female diploid cells is a manifestation of a single X-chromosome. A cell with 2 sets of autosomes and 2 X-chromosomes is found to have one heteropyknotic X during interphase. The XO or XY cell has no heteropyknotic X. In cells with 2 sets of autosomes and more than 2 X-chromosomes, more than one X may be heteropyknotic, permitting a single X to remain isopyknotic to the autosomes. 4. The greater number of chromosomal anomalies have been found to involve the sex chromosomes. This may reflect the heterochromatic nature of the X and Y, permitting unbalanced conditions to be viable for the organism. Only one monosomic condition, the XO, has thus far been described. No trisomic conditions for the larger autosomes have been detected. 5. The Y-chromosome is a male-determining body. The only cases in which a testis is present in the absence of a Y concern hermaphrodites. In other situations, the Y in combination with one or more Xs influences development in a male direction. The female-determining potentialities of the X are not so clearly delineated as the wide range of phenotypes associated with the XO condition seems to indicate. The association of mental retardation with anomalies of the X-chromosome is unusually prevalent. 6. Clinical conditions characterized by primary gonadal failure or intersexuality have been clarified by chromosomal analyses. There is need for detailed studies of cells from many tissues to delineate the role of mosaicism, especially as it may pertain to hermaphroditism. 7. Nondisjunction, influenced by maternal age, is an important etiological basis for the existence of trisomic states. 8. For the pediatrician, the studies on Mongolism are of primary importance. The genetic aspects of the condition have been clarified and a basis for the familial occurrence emphasizes the necessity of chromosomal analyses in providing information in regard to future pregnancies in young mothers with affected children. 9. The presence of an attenuated chromosome 21 or 22, the Ph1 chromosome, is associated with chronic myeloid leukemia.

Cloning and expression of the cDNA encoding rabbit liver carbonyl reductase.

Two cDNA sequences encoding rabbit carbonyl reductase (CBR) were cloned from a lambda gt10 rabbit liver cDNA library. The rabbit cDNAs coded for a protein with 84% identity to human CBR. Transient expression of the two rabbit cDNA sequences in COS7 cells increased both quinone reductase and aldo-keto reductase activities. These data demonstrate that CBR cDNAs from rabbit and human tissues code for similar proteins.

Rat liver NAD(P)H : quinone oxidoreductase : cDNA expression and site-directed mutagenesis

Rat liver NAD(P)H:quinone oxidoreductase cDNA was cloned and expressed in a eukaryotic cell expression plasmid containing a cytomegalovirus (CMV) promoter. Transient expression of enzyme activity and RNA transcription were measured in COS7 cells. The expressed quinone reductase has kinetic properties similar to the rat liver enzyme and is inhibited by dicourmarol, a known inhibitor of NAD(P)H:quinone oxidoreductase. Site-directed mutagenesis experiments carried out using this expression system revealed possible regions involved in NAD(P)H binding.

Production and Relative Frequency of Maternally Influenced Lethals in Drosophila melanogaster

A method for isolating maternally influenced sex-linked recessive lethals in Drosophila melanogaster has been outlined. By this procedure we obtained mutations that were lethals in that they killed the homozygous or hemizygous lethal progeny of homozygous lethal-bearing female parents. The lethals were maternally influenced in that these classes of progeny survived from heterozygous lethal-bearing female parents. Apparently the latter female parents provided an egg cytoplasm sufficient for progeny survival, and the former ones did not. These lethals were classified as Type I because the daughters of homozygous lethal-bearing females could be rescued by sperm bearing the wild-type allele. With ethyl methane sulfonate as the mutagen, this class of lethals occurred with a frequency of 0.21% and comprised 0.73% of all sex-linked recessive lethals.

Carbon dioxide induced changes in the electroretinogram of Drosophila unaccompanied by altered phototactic behaviour

Abstract Some phototactic mutants of Drosophila melanogaster have been shown to have abnormal ERGs. In the presence of increased CO 2 , normal flies have ERGs resembling those of the mutants while retaining their characteristic phototactic response. It is concluded that an abnormal ERG is not in itself an indication of abnormal phototactic behaviour.

Autoradiographic studies ofDrosophila gonads following the feeding of14C labelled formaldehyde

SummaryMale and female larvae ofDrosophila melanogaster at 24, 48, 72 and 96 hours of age were placed upon a standard type of food to which14C labelled formaldehyde had been added. They were left to feed for specified periods of time and then removed and autoradiographs were prepared. The technique used demonstrated that formaldehyde enters the male and female gonad with penetration equally in all regions. The differential sensitivity demonstrated by genetic techniques seems, thus, to be a consequence of differential response to the presence of formaldehyde rather than to differential penetration.It has been pointed out that a positive autoradiograph indicates the presence of14 C atoms but does not tell anything about the compounds in which they are present.

Genetic effects of tritiated thymidine and evidence for its incorporation into a cytoplasmic component of the adult testis of Drosophila Melanogaster

Abstract Sex-linked recessive lethals were induced by the injection of [ 3 H]thymidine into male imagos of Drosophila melanogaster . Elevated mutation rates were observed earlier than the tenth day post-injection when the first labeled sperm cells are expected to be available for fertilizations. Radioautographs prepared from testes of males taken from successive broods disclosed a cytoplasmic label which was removable by DNAase. It is suggested that radiations from the labeled cytoplasmic DNA were responsible for the mutations produced in the early broods. The nature of the cytoplasmic body which had incorporated the [ 3 H]thymidine is not known.