Nature of telomere dimers and chromosome looping in human spermatozoa.

Specific and well-organized chromosome architecture in human sperm cells is supported by the prominent interactions between centromeres and between telomeres. The telomere-telomere interactions result in telomere dimers that are positioned at the nuclear periphery. It is unknown whether composition of sperm telomere dimers is random or specific. We now report that telomere dimers result from specific interactions between the two ends of each chromosome. FISH using pairs of subtelomeric DNA probes that correspond to the small and long arms of seven human chromosomes demonstrates that subtelomeres of one chromosome are brought together. Statistical analysis confirmed that telomere associations could not result from the random proximity of DNA sequences. Therefore, chromosomes in human sperm nuclei adopt a looped conformation. This higher-order chromosome structure is most likely required for chromosome withdrawal/decondensation during the early fertilization events leading to zygote formation.

Deletion of the long arm of chromosome 5 (5q-) as a secondary event in the course of refractory anemia.

A 54-year-old chemical plant worker developed mild pancytopenia, with normal bone marrow morphology. Normal bone marrow cytogenetics were documented. The patient developed worsening anemia 5 years into his course. The bone marrow morphology remained normal, but four of 30 bone marrow metaphases examined showed deletion of the long arm of chromosome #5. Eight years into his course, the patient developed severe thrombocytopenia, and his bone marrow became hypercellular, with dysplastic changes. Deletion of the long arm of chromosome #5 was seen in all of 21 bone marrow metaphases examined. There had been no new exposure to potential mutagens during the course of the patient's illness. The occasional documentation of the late appearance of cytogenetic abnormalities during the course of clonal hematopoietic disorders implies that, in some cases at least, chromosomal abnormalities may not be primary pathogenetic events. The full expression of clonal disorders may require several pathogenetic events, which may occur in variable order.

A case of rhabdomyosarcoma of the bladder with a (2;5) chromosomal translocation in peripheral lymphocytes.

Chromosome analysis was performed on peripheral blood lymphocytes of a patient with rhabdomyosarcoma of the urinary bladder. It showed a reciprocal t(2;5) translocation with the breakpoints at 2q37.3 and 5q31.3. This is the first report of such an anomaly in the peripheral lymphocytes of a patient with rhabdomyosarcoma of the urinary bladder.

Light and scanning electron microscopy of the same human metaphase chromosomes.

A technique has been developed to examine the same G-banded human metaphase chromosomes, first in the light microscope and then in the scanning electron microscope (SEM). A structural involvement in chromosome banding was confirmed by a positional correlation between the G-positive bands observed in the light microscope and the circumferential grooves between the quaternary coils of the metaphase chromosomes, observed in the SEM. In further support of this the regions between the grooves showed a positional relationship with the G-negative or reverse (R) bands. The examination of slightly extended metaphase chromosomes in the light microscope demonstrated that the G-banding pattern corresponded to that described by the Paris nomenclature for metaphase chromosomes. The arrangement of the circumferential grooves of the same chromosomes, observed in the SEM, was shown to relate to that described by the Paris nomenclature for prometaphase chromosomes. Therefore, using the SEM it is possible to demonstrate the details of prometaphase banding in metaphase chromosomes.

Persistent Epstein-Barr virus infection associated with monosomy 7 or chromosome 3 abnormality in childhood myeloproliferative disorders.

This report deals with myeloproliferative disorders associated with chronic, persistent Epstein-Barr virus (EBV) infection and with monosomy 7 and aberrations concerning chromosomes 3 and 5. Altogether five children were affected, their age ranging from 1 to 4 years at time of clinical diagnosis. Principal symptoms were: hepatomegaly, splenomegaly, recurring upper respiratory tract infection and anaemia. The serum IgG level remained persistently increased. Anti EBV antibody concentrations were measured over a period of 9 months to 6 years, demonstrating persistently increased concentrations of IgG antibodies to viral capsid antigen (VCA) and against early antigen (EA). In three patients IgA antibodies were also studied and were found to be elevated. Within 2-5 years two children developed chronic myelomonocytic leukaemia from the chronic myeloproliferative syndrome. A third patient who initially was diagnosed as chronic myelomonocytic leukaemia developed acute leukaemia within a period of 12 months. A fourth patient with myeloproliferative syndrome went into spontaneous remission after an observation period of 2 years. A fifth patient, the only one with translocation t(3;5)(q27;q33), displayed symptoms and a clinical course that can best be characterized as juvenile chronic myelocytic leukaemia. The clinical, haematological, serological and cytogenetic findings may be related.

A rare heterochromatic variant of chromosome 4.

A variant chromosome 4 with a large G positive heterochromatic block is described and discussed in relation to chromosome 4 heteromorphisms observed with other banding techniques. The extra heterochromatin is C positive and fluoresces brilliantly with Q banding, but differs from Yqh with some methods of staining.

Balanced rearrangement of chromosomes 2, 5, and 13 in a family with duplication 5q and fetal loss.

We have studied a family in which a mother and daughter (the proposita) had the karyotype 46,XX,ins(2;5),t(5;13). The mother had four spontaneous abortions, a mentally retarded son with duplication (5q), and a daughter who died at 3 months. The proposita had a phenotypically abnormal abortus. Rearrangements involving several chromosomes are very rare. Observations on this family are consistent with the predicted high likelihood of reproductive loss.

Assignment of the structural gene encoding human aspartylglucosaminidase to the long arm of chromosome 4 (4q21----4qter).

The structural gene for the human lysosomal enzyme aspartylglucosaminidase (AGA) has been assigned to chromosome 4 using somatic cell hybridization techniques. The human monomeric enzyme was detected in Chinese hamster-human cell hybrids by a thermal denaturation assay that selectively inactivated the Chinese hamster isozyme, while the thermostable human enzyme retained activity. Twenty informative hybrid clones, derived from seven independent fusions, were analyzed for the presence of human AGA activity and their human chromosomal constitutions. Without exception, the presence of human AGA in these hybrids was correlated with the presence of human chromosome 4. All other human chromosomes were excluded by discordant segregation of the human enzyme and other chromosomes. Two hybrid clones, with interspecific Chinese hamster-human chromosome translocations involving the long arm of human chromosome 4, permitted the assignment of human AGA to the region 4q21----4qter.

Familial Wolf's syndrome with a hidden 4p deletion by translocation of an 8p segment. Unbalanced inheritance from a maternal translocation (4;8)(p15.3;p22). Case report, review and risk estimates.

This is the case report of a patient with Wolf's syndrome having a monosomy 4pter----p15.3 and an additional trisomy 8pter----p22, derived from a maternal balanced translocation t(4;8)(p15.3;p22) after 2:2 disjunction and adjacent-1 segregation. The patient's phenotype is presumably slightly modified by the trisomic 8p segment. Literature analyses indicate that phenotypic "hybrids" with traits of monosomy 4p and of other autosomal segment trisomies exist. The dermatoglyphics of the patient were not highly characteristic for Wolf's syndrome. Also the dermatoglyphics of the balanced translocation carriers were unspecific and did not reflect the carrier status. Pedigree analyses of 46 reported families with reciprocal translocations involving the short arm of chromosome 4 show a high risk (20.5% +/- 4.6%) for unbalanced offspring (trisomy or monosomy 4p) after 2:2 disjunction and adjacent-1 segregation, if the breakpoint in the recipient chromosome is terminal and the resulting imbalance concerns the 4p segment only. It is considerably lower (4.5% +/- 2.5%) if the breakpoint in the recipient chromosome is subterminal, as in the reported case, and the resulting imbalance concerns other chromosome segments additionally to the 4p segment. In both instances, the risk decreases with increasing segment length. The risk for unidentified abortions, stillbirths or neonatal deaths is also high in these families (about 40%). The frequency of progeny with balanced compared to progeny with normal karyotype corresponds to the expected 50% for alternate segregation.

Interstitial deletion of the short arm of chromosome 4.

A 17 year old girl investigated for mental retardation and minor anomalies was found to have an interstitial deletion of 4p. Her clinical and cytogenetic findings are compared with previous reported case of interstitial 4p deletion and with terminal 4p--deletions (Wolf-Hirschhorn syndrome).

Five generations of t(4;8)(q35;q13) leading to a case of partial 8q trisomy with consideration of potential pregnancy outcomes from translocation carriers.

We describe a female infant with partial trisomy 8q who has microphthalmia, a cleft palate, micrognathia and a heart defect. Her dysmorphogenetic features closely resemble the characteristic pattern seen in the 17 cases thus far reported in the literature. Her chromosomal defect was caused by an unbalanced translocation, inherited through her father, and found to have been transmitted through at least 5 generations. Recently developed models designed to predict the most probable mode of unbalanced segregation from the meiotic quadrivalent and the likelihood that a chromosomally unbalanced fetus will survive to term are applied to this family's translocation. Also, the frequencies of potential reproductive outcomes from carriers of this translocation generated from empiric data are considered as a requisite aid to genetic counseling.

Fourth International Workshop on Chromosomes in Leukemia 1982: Deletion of 5q.

In 36 cases with del(5q) examined, a type A2 deletion (q14 or q15q33) represented 56% of all cases, a type A1 deletion (q11 or q12q33) was present in 33%, and a type B deletion (q22q33) occurred in 11% of cases; therefore, all deletions were interstitial. The critical region for these cases was q22 to q33 or q34. Additional abnormalities were present in 85% of del(5q) cases; the most frequent additional abnormality was loss of one #7 (28%).

Familial balanced insertion (5;10) and monosomy and trisomy (10) (q24.2----q25.3).

The phenotype of a boy with monosomy of a small segment of chromosome (10) (q24.2----q25.3) is described. In his family a balanced insertion (5;10) is found in three generations. Moreover there are two persons who are trisomic for the same small segment of chromosome 10 for which the boy is monosomic.

A structural analysis of the role of the nuclear matrix and DNA loops in the organization of the nucleus and chromosome.

The interphase nucleus is characterized by a nuclear matrix structure that forms a residual scaffolding composed of approximately 10% of the total nuclear proteins. The nuclear matrix contains residual elements of the pore-complex and lamina, the nucleolus, and an intranuclear fibrous network that provides the basic shape and structure of the nucleus. In the interphase nucleus this nuclear matrix has been reported to be a central element in the organization of DNA loop domains and to contain fixed sites for DNA replication and transcription. In this study, we have analysed the role of the nuclear matrix and the DNA loop domains in the organization and structure of the number 4 human chromosome. A model is proposed that closely approximates the observed structural dimensions of this chromosome. The model is composed of 30 nm diameter filaments formed from a solenoid of six nucleosomes per turn. This 30 nm solenoid filament is organized as loops of DNA each containing approximately 60 000 base-pairs; each loop is anchored at its base to the nuclear matrix. A radial loop model containing 18 of these loops per turn forms a new unit of chromosome structure termed the miniband. Approximately 106 of these minibands are arranged along a central axis to form the final chromatid. The role of the nuclear matrix in this organization is presented. The accuracy of the proposed model is tested by comparing its features with the known properties of the number 4 human chromosome.

[Polymorphism of the chromosome Q-segments in phenotypically healthy persons of the native population of the Latvian SSR]. / Polimorfizm Q-segmentov khromosom u fenotipicheski zdorovykh lits korennogo naseleniia Latviiskoi SSR.

Chromosomes of 140 healthy adult individuals from the Latvian population were investigated by the fluorescence method. Data on the polymorphism patterns are presented for chromosomes 3, 4, 13, 14, 15, 21, 22 and Y. No differences were revealed between sexes in the frequency of highly fluorescent segments of autosomes. The frequencies of homozygotes and heterozygotes for certain chromosome segments did not correspond to the Hardy-Weinberg distribution.

[Syndrome of terminal deletion of the long arm of chromosome 4. Apropos of a personal case with a review of the literature]. / Le syndrome de deletion terminale du bras long du chromosome 4. A propos d'un cas personnel avec revue de la litterature.

With one personal case and thirteen cases from literature about distal deletion of the long arm of chromosome 4 (4 q-), authors try to describe a clinical syndrome related to deletion of segment 4 q 31 leads to q ter. This syndrome includes a normal intrauterine growth, a growth and mental retardation. Morphological abnormalities consist in microcephaly, palato-cheiloschisis with micrognathia, hypertelorism with epicanthald folds, large nose bridge with anteverted nases, various anomalies of ears; clinodactily of Vth finger and toe, various cardiac defects. New banding techniques (prometaphase) have led to more precise delineation of break point, but this very distal deletion could not bring any new information for the gene mapping.

The bone marrow karyotype in seventeen cases of refractory anemia with excess of blasts (RAEB).

The bone marrow karyotype was studied in 17 patients affected by refractory anemia with excess of blasts (RAEB). A cytogenetic finding common to nearly all the cases is hypodiploidy, present in even quite high percentages. In 3 patients were identified the same interstitial deletion of the long arm of a chromosome 5, present in a percentage varying between 30% and 65%. The presence of this chromosomal anomaly appears to correspond to a slower development of the illness and transformation into acute leukemia seems rare or delayed.

"Pure" monosomy 21 pter leads to q21 in a girl born to a couple 46,XX,t(14;21)(p12;q22) and 46,XY,t(5;18)(q32;q22).

A two-year-old girl with a "pure" 21pter leads to q21 monosomy secondary to a 3:1 segregation of a maternal translocation t(14;21)(p12;q22) is described. The father's karyotype was 46,XY,t(5;18)(q32;q22). This observation permits to further delineate the 21q proximal monosomy syndrome and to comment the very rare finding of a couple in which both partners have different reciprocal translocations.