Klaus Patau

Absorption microphotometry of irregular-shaped objects

SummaryA new microphotometric method (mainly for the evaluation of microchemical color reactions) which uses measurements at two wave lengths (developed byOrnstein and, independently, by the author) is presented in a form which greatly reduces the computational labor (for an illustration, see Table 3).

A new autosomal trisomy syndrome: multiple congenital anomalies caused by an extra chromosome

Summary Two patients are described who died in early infancy. Each displayed similar complexes of congenital anomalies of which the following ones were found in both: low-set and malformed ears, small mandible, flexion deformities of the fingers, anomalous feet, interventricular septal defect, spasticity with probable mental defect, and diverticulum of the intestine. The chromosome number was 47, the extra chromosome appearing to be the same one in each instance; it belongs to the E group in the classification of Patau and associates. 1 The mothers of both patients were of advanced age at the time of conception.

Abnormal X chromosomes in man: Origin, behavior and effects

SummaryAbnormal human X chromosomes, their origin, phenotypic effects, and especially their inactivation are reviewed. In cases of balanced reciprocal X-autosomal translocations (Table 2), almost always the normal X is inactivated. Most of such patients suffer from gonadal dysgenesis, which might be caused either by functional hemizygosity for a recessive gene or by a position effect resulting from a rearrangement involving a certain region of Xq. In cases with 46 chromosomes and an unbalanced X-X translocation, the translocation chromosome is inactivated; in most such patients, an X0 cell line is also present (Table 3). Some of the possible modes of origin of such translocations are presented in Fig. 1; these also explain the occurrence of the X0 cell lines. In patients with 46 chromosomes and an unbalanced X-autosomal translocation, the whole translocation chromosome seems to be inactivated, if the autosomal segment is attached to Xp. If on the other hand the segment is, attached to Xq, inactivation seems to be limited to the X part (Fig. 3).There are reasons for assuming the existence of an inactivation center without which an X chromosome cannot be inactivated. This center would be located on the proximal part of Xq. (Abnormal chromosomes with two such centers tend to form bipartite Barr bodies.) If 2 X chromosomes possess an inactivation center each, they would originally be inactivated at random, it then being left to selection to determine the final frequencies of the cell lines with different inactivation patterns.The phenotypic effects of monosomy, disomy and trisomy for different parts of Xp and Xq are discussed (Fig. 3).

The D1 trisomy syndrome

This paper further defines the phenotype which results from trisomy for a particular autosome of the D group (13–15) in the cells of the developing embryo. From our 7 patients plus 7 additional cases reported by others, the principal pattern of anomalies in these grossly malformed babies is presented. Though there is variability in the expression of the D 1 trisomy from patient to patient, the total pattern of anomalies is specific enough to allow for clinical recognition in the nursery for newborn infants. As with the other autosomal trisomy syndromes (Downs syndrome and the 18 trisomy syndrome), this condition occurs more commonly at older maternal age.

The No. 18 trisomy syndrome.

Summary Trisomy of chromosome No. 18 results in a characteristic pattern of multiple congenital anomalies of which apparent mental retardation with moderate hypertonicity, lowset malformed ears, small mandible, flexion of the fingers with the index finger overlying the third, and severe failure to thrive constitute the most prominent clinical abnormalities. It usually leads to death in early infancy. The syndrome has been of sporadic occurrence. Its frequency increases with advancing maternal age.

Center for Barr body condensation on the proximal part of the human Xq: a hypothesis

The following hypothesis is put forward: X chromatin in man condenses around a center which is situated on Xq at a short distance from the centromere. The hypothesis is based on, and explains, two classes of observations. (1) Abnormal X chromosomes that have the assumed center in duplicate form bipartite Barr bodies in part of the cells. The frequency of bipartite bodies and the distance between the two parts seem to be determined by the distance between the postulated centers. (2) A large number of variously abnormal X chromosomes have been described. Almost all of them possess the postulated center and it seems possible that the very few apparent exceptions represent misidentifications of chromosome Xq — as isochromosome i(Xp). According to the hypothesis, chromosomes lacking the center would form no Barr body and therefore presumably would not be inactivated, thus leaving the cell severely unbalanced. Furthermore, absence of the center might interfere with the viability of the chromosome itself.

The DNA-content (Feulgen) of nuclei during mitosis in a root tip of onion

SummaryThe microphotometric two-wavelength method is demonstrated to permit, even with only an improvised optical set-up, DNA-measurements which would not be possible, at any rate not with a comparable accuracy, with the conventional method.The data, in agreement with earlier results, show that the largest interphase nuclei in the root meristem have already completed their DNA-synthesis.The mean DNA-contents per set of chromatids at late interphase, prophase, and telophase, appeared to be virtually identical. A natural variation in DNA-content, if any, between individual nuclei at these stage would have a coefficient of variation of significantly less, and most likely much less, than 7.3%. The data from metaphase to middle anaphase are, for technical reasons, not yet conclusive. An indicated, moderate, excess of Feulgen-dye in these as compared with earlier and later stages may not be real.The results are fully compatible with a working hypothesis of strict constancy of the DNA-content per chromatid and of its precise doubling during DNA-synthesis (for necessary qualifications see the discussion). It is pointed out that apparently contradictory results by certain other authors do not, for methodological reasons, yet establish disproof of this hypothesis.

Partial-trisomy syndromes

SummaryOne of the autosomes of the C group (6–12), C′, can sometimes be identified by a secondary constriction.A mother and her daughter, both afflicted with the oral-facialdigital (OPD) syndrome, are shown to be partially trisomic for an inner segment of C′, this segment having been inserted into chromosome 1. The other chromosome 1, the two chromosomes C′, and the rest of the complement of 46 chromosomes appear normal.In four other OFD patients no chromosomal abnormality was detected. Nonetheless, it is concluded that the OFD syndrome is generally caused by partial trisomy for a specific region of C′. The presence of the inserted extra segment would usually escape microscopical detection.

The relation of DNA synthesis and mitosis in tobacco pith tissue cultured in vitro

SummaryDNA synthesis and mitosis were initiated in cultured tobacco pith tissue by means of IAA and kinetin. DNA classes were determined by microspectrophotometric measurements (Feulgen); autoradiographs (tritiated thymidine) served to ascertain whether or not nuclei had undergone DNA synthesis during culture.All mitoses in “new” cells (resulting from divisions in culture) were diploid and had been preceded by DNA synthesis in culture.Whereas many of the “old” cells (which had not previously divided in culture) found in diploid or polyploid mitosis had undergone DNA synthesis during culture, others had not. Such non-radioactive mitoses still occurred after 16 days.In view of this, a 4 C nucleus in differentiated tissue should be considered as potentially both diploid and tetraploid, for it appears impossible to predict whether it would, upon restoration of conditions conducive to DNA synthesis and mitosis, enter a diploid mitosis or, after undergoing DNA synthesis, a tetraploid one.A high nuclear DNA content seems to have a much more inhibiting effect on the onset of DNA doubling than on that of mitosis.Somatic polyploidization is understood as the result of two DNA doublings between which mitosis was omitted, or aborted, or in effect undone by a failure of cytokinesis leading to fusion during a later mitosis.

Autoradiographic and microspectrophotometric studies of DNA synthesis in excised tobacco pith tissue

SummaryPith tissue was cultured on modified White’s nutrient medium supplemented, except for controls, with 2 mg/l of IAA and/or 0,5 mg/l of kinetin. For autoradiographs sections were used from tissue grown on medium containing tritiated thymidine.Nuclear DNA contents (Feulgen) were measured by the microspectrophotometric two-wavelengths method. No fading of Feulgen dye in nuclei was found in 11 weeks, in contrast to considerable fading observed in earlier work when a different batch of basic fuchsin had been employed.Counts of radioactive nuclei in autoradiographs agreed well with microspectrophotometric results on the occurrance of DNA synthesis.In control cultures, with or without tritiated thymidine, DNA doubling took place in about 20% of the nuclei during the first two days but in few, if any, thereafter.It was confirmed that kinetin, as well as IAA, increases the frequency of nuclei undergoing DNA synthesis. However, IAA, in contrast with kinetin, still induced considerable DNA doubling after two days. Continued cell reproduction was maintained only in the presence of both substances.