Harvey Dosik

Human chromosomal heteromorphisms: nature and clinical significance.

Publisher Summary The heteromorphic chromosomes of the human genome can be classified by size, position, staining intensity, or any combination of these types using various banding techniques, such as QFQ (Q-bands by fluorescence using quinacrine), CBG (C-bands by barium hydroxide using Giemsa), and RFA (R-bands by fluorescence using acridine organe). The classification of different types of heteromorphisms is based on estimation rather than actual measurements. Moreover, variation is continuous rather than discrete. However, several attempts are made to classify them on the basis of arbitrary scales and different codes (levels) are assigned. Chromosomal heteromorphisms found in human chromosomes provide a useful tool for several studies because they are inherited in a Mendelian fashion, are stable, and are presumed to have a low mutation rate. By using heteromorphic markers of chromosome 21, the origin of the extra chromosome in Down syndrome can be determined. Applications of heteromorphisms as markers is in elucidating the chromosomal mechanisms involved in the production of mosaics, in studying chimeras, and in following the fate of transfused or transplanted cells.

An improved method for photographing fluorescent human chromosomes

In the photography of sequentially QFQ and RFA banded chromosomes, the fading problem can be solved by reducing exposure time. This can be accomplished by choosing the right light source, filter combinations, type of film and developer. Three different systems were employed to record the exposure time during photography. A ‘Vertical Illuminator III RS’ with a 50 w/AC mercury burner equipped with 400–490, BG 12–BG 38 excitation filters and 510 barrier filter was found to be the most efficient and satisfactory. QFQ banded chromosomes can be photographed within 3–5 s and RFA banded chromosomes within 10–15 s with this system.

Incidence of major chromosomal abnormalities in a referred population for suspected chromosomal aberrations: a report of 357 cases.

The present report describes the cytogenetic findings in 357 cases referred for suspected chromosomal abnormalities because of abnormal clinical features. Chromosomal anomalies were found in 97 (27.2 %) of the cases studied. A significantly high rate of chromosomal abnormalities was found in a population with clinical abnormalities in comparison to an unselected population (0.48–0.55 %).

Frequency of RFA colour polymorphisms of human acrocentric chromosomes in Caucasians: interrelationship with QFQ polymorphisms

One hundred normal Caucasians were studied by sequential QFQ and RFA in order to estimate the type and frequency of variation. Colour variants were classified into 1 of 6 colours by RFA and intensity variations into 1 of 5 levels by QFQ. The interrelationship between QFQ and RFA variants was also examined. It was found that there was no consistent relationship between negative or brilliant QFQ variants and the various colours observed with RFA. RFA colour polymorphisms for chromosomes 13, 14, 15, 21 and 22 were 33.0, 38.0, 28.0, 50.0 and 24.5% while QFQ frequencies were 56.5, 10.0, 10.0, 15.5 and 10.0% respectively. RFA is especially useful in studying the inheritance of chromosome 21.

The technical variables associated with the frequencies of QFQ, RFA and CBG heteromorphisms of human chromosomes.

In the 1971 Paris Conference (1972) it was established that certain regions of human chromosomes show remarkable heteromorphisms. These are the short arm of acrocentric chromosomes, the secondary constriction regions of chromosomes 1, 9, 16, and the distal 2/3rd of the long arm of the Y and the centromere of chromosomes 3, 4, and 5. There are several technical variables which affect the frequency of these heteromorphisms. These include quality of culture, age of slide, photography (filter, etc.), method of printing and method of scoring (criteria). Several other variables in the production of QFQ, RFA, and CBG heteromorphisms are discussed. In order to compare results from different laboratories these variables must be taken into consideration.

Inherited Aplastic Anaemia with Increased Endoreduplications: a New Syndrome or Fanconi's Anaemia Variant?

Summary. TWO sisters with aplastic anaemia without other congenital anomalies are described. Peripheral blood cytogenetic studies revealed an increase in endoreduplications in the absence of other unstable chromosome anomalies. Increased expression of T‐antigen following SV40 virus infection in vitro was demonstrated in both sisters, as well as other normal family members. We feel that these patients represent a variant of Fanconis anaemia. The importance of performing chromosome studies in idiopathic aplastic anaemia is emphasized.

Structural organization of chromosomes of the Indian muntjac (Muntiacus muntjak)

The identification, morphology, and banding pattern of the chromosomes of the Indian muntjac (Muntiacus muntjak) are described. A diagrammatic representation of the banding pattern as revealed by various techniques is presented following the nomenclature suggested by Paris Conference (1971) for human chromosomes. The Y2 chromosome and the neck of the X chromosome are late replicating based on observations made with the use of a bromodeoxuridine plus Giemsa technique. Most of the G-bands are early replicating, contrary to earlier findings based on autoradiography.

Heteromorphisms of the Philadelphia (Ph1) Chromosome in Patients with Chronic Myelogenous Leukaemia (CML). I. CLASSIFICATION AND CLINICAL SIGNIFICANCE

Summary In patients with chronic myelogenous leukaemia (CML), we have found the break points on the long arm of chromosome 22 (22q) are variable (heteromorphic or polymorphic). Consequently, the Philadelphia (Ph1) chromosome is heteromorphic in size for the long arm. Based upon the break points and the relative size of chromosome 22, four types of Ph1 chromosomes are proposed. They are: Types I (very large), II (large), III (average) and IV (small) with the break points at bands 22q13.3, 22q13.1, 22q12 and 22q11.3, respectively. The break points are arbitrary and should not be considered absolute since they are based on length differences. In two cases the Ph1 chromosome involved a translocation between chromosome 9 and 22, and the other two cases chromosome 1 or 12. Because Types I and II are hard to recognize by conventional techniques, the RFA technique (R. band by fluorescence with acridine orange) must be performed on all cases. An earlier contention that only chromosome 22 band 12 is concerned with abnormal myeloid cell proliferation in human leukaemia is rejected. Furthermore, break points are not restricted at the junction of 22q1 and q2 and 22q2 and q3 and can happen anywhere on the long arm of chromosome 22.

A possible cause of non-disjunction of additional chromosome 21 in Down syndrome

SummaryA possible cause of non-disjunction of chromosome 21 in Down Syndromes has been cytogenetically evaluated by examining the parents by Ag-staining technique. In all the cases studied so far, the contributing parents have active ribosomal cistrons on both chromosomes 21 i.e. both chromosomes are stained positively by silver staining. These results show that the active NORs might play an essential role in meiotic non-disjunction. Furthermore, the preliminary results demonstrate that the acrocentric associations of homologous and non-homologous nature involving chromosome 21 are the most frequent in the contributing parent which may further indicate the role of multiple cellular factors affecting the associations in promoting the non-disjunction in addition to active NORs. The possible mechanisms regarding the non-disjunction of chromosome 21 have been described.

Alpha Thalassaemia in American Blacks: a Study of a Family with Five Cases of Haemoglobin H Disease

Summary. Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2–6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in α globin production with an average α/β ratio of 0.31 (range 0.22–0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either α‐that‐1 (average MCV of 65.2 fl; range 59–70) or α‐thal‐2 (average MCV 79.6 fl; range 74–88). A subject with α‐thal‐1 trait had an α/β ratio of 0.56; the average for five cases of α‐thal‐2 was 0.73. One other family member was thought to be homozygous for α‐thal‐2 trait and exhibited an MCV of 65 fl with an α/β ratio of 0.5. These data reconfirm that in Blacks with α thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in α and β globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater α globin production in that population of thalassaemics.