Partial Trisomy Of Chromosome Research Articles

Structural brain imaging abnormalities associated with schizophrenia and partial trisomy of chromosome 5.

Chromosomal abnormalities occurring in association with mental illness provide a unique opportunity to study the interaction of genetic abnormalities and the brain in mental illness. Four individuals from a family in which schizophrenia was found to cosegregate with a partial trisomy of chromosome 5 were studied with computed tomography and magnetic resonance imaging. Temporal lobe atrophy was found in the two trisomic males and in the asymptomatic balanced translocation female. In addition, a large cavum septum pellucidum and a cavum vergae were found in the older trisomic individual. Scans from the normal male were free of abnormalities. These results suggest that molecular studies of the translocation breakpoints in this chromosomal abnormality may be of interest, and encourage further studies of brain structure in other chromosomal abnormalities associated with psychosis.

Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia

Two independent lines of evidence support the localization of a schizophrenia susceptibility locus to the proximal long arm of chromosome 5. A partial trisomy of chromosome 5 (5q11.2–q13.3) cosegregates with the disorder in a Canadian family of Chinese descent, and DNA markers from proximal 5q cosegregate with schizophrenia (plus related disorders) in families of British and Icelandic descent. We constructed a human:hamster hybrid cell line (HHW 1064) whose only human complement is a chromosome 5 that is missing the trisomic region associated with schizophrenia. In combination with a “matched” cell hybrid (HHW 105) containing an intact chromosome 5, we physically mapped DNA markers relative to the trisomy. “Schizophrenia-linked” DNA markers p105–153Ra (D5S39) and p105–599Ha (D5S76) map within the trisomy and proximal to the 5q11.2 breakpoint, respectively. The hybrid cell lines HHW 105 and HHW 1064 together provide a means to identify and generate syntenic DNA markers to further investigate the location of a schizophrenia locus.

Cytogenetic abnormalities in tumors of patients with von hippel-lindau disease

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes the development of benign and malignant tumors in several organ systems. Tumors causing significant morbidity include retinal angioma, cerebellar hemangioblastoma (CH), renal cell carcinoma (RCC), and pheochromocytoma (Pheo). Cytogenetic studies of tumors in VHL patients are rare. Cytogenetic findings in tumors from 12 patients with VHL disease, including four RCCs, three CHs, and five Pheos are presented. Three of the four RCC cases were abnormal. Monosomy 3 or a deletion of 3p was present in all three abnormal cases. Complete or partial trisomy of chromosome 5 was present in two cases. A deletion of 14q, trisomy 7, and a missing Y were each observed in one case. These findings indicate that a deletion of 3p may be a primary cytogenetic change in RCCs associated with VHL disease in addition to playing a role in sporadic RCC. Duplications of 5q and deletions of 14q may be important secondary changes in the progression of the malignant phenotype. No visible cytogenetic abnormalities were observed in the three CHs, or in four of the Pheos. One of the five Pheos was found to exhibit mosaic trisomy 7; its significance is unclear at the present time.

Eye Tracking Dysfunction is Associated With Partial Trisomy of Chromosome 5 and Schizophrenia: A Response-Reply

In Reply.— Our case study revealed that a proband and his maternal uncle, both of whom had partial trisomy of chromosome 5 and schizophrenia, also had abnormal smooth-pursuit eye tracking. The proband's mother, father, and brother, who had neither any psychiatric disorder nor the partial trisomy, displayed very good eye tracking performance. Although we are pleased that Holzman et al found these data supportive of their latent trait hypothesis, we do not share their reservations and concerns. If we assume that schizophrenia in the proband and uncle arose because they had the chromosomal anomaly, then finding abnormal pursuit tracking in the nonschizophrenic family members would not support the latent trait hypothesis. This family is interesting presumably because the trisomic individuals possess a special genotype (partial trisomy chromosome 5) associated with schizophrenia, while the other members of the family do not. There is, therefore, no reason to expect the nontrisomic, psychiatrically healthy

Rearrangements of chromosome 3 in nonfamilial renal cell carcinomas from Japanese patients.

Cytogenetic studies were successfully carried out in 5 tumor tissues from Japanese patients with nonfamilial renal cell carcinoma, histologically diagnosed as clear cell subtype. Mitotic cells were obtained by a combined method of enzymatic disaggregation and short‐term culture (6–12 days). The modal chromosome numbers were found to be diploid or near‐diploid in all the cases examined. Every case showed characteristic structural and numerical abnormalities. Rearrangements in the short arm of chromosome 3 were observed as clonal abnormalities in all the cases, including a translocation t(3;6) resulting in a partial loss of 3p (3 cases), a terminal deletion of 3p (one case) and 2 different translocations involving 3p and 8p (one case). The other clonal abnormalities were a whole or partial trisomy of chromosome 7 and a loss of Y chromosome. The overall results in the present study were consistent with those of our previous data in American patients, and suggest that the rearrangements of chromosome 3 leading to a partial loss of its short arm may play primary and significant role(s) in the development of renal cell carcinoma.

PARTIAL TRISOMY CHROMOSOME 5 COSEGREGATING WITH SCHIZOPHRENIA

Schizophrenia was associated with a distinct autosomal abnormality in two related mildly dysmorphic individuals. The finding of cosegregation of schizophrenia and a partial trisomy of chromosome 5 in the family suggests a potential location of a gene or genes linked to schizophrenia.

Altered chromatin structure associated with a partial trisomy of chromosome 7 in the mouse.

The chromatin of a mouse that is trisomic for part of chromosome 7 was investigated. Chromatin from trisomic tissue has a smaller average nucleosome DNA repeat length than chromatin from tissue taken from normal diploid littermates. DNA of the nucleosome cores is the same size in both normal and trisomic tissues. Not all of the nucleosome monomers have different repeat lengths. Normal and trisomic mouse kidney cells in tissue culture maintained their nucleosome repeat-length differences.

Cytogenetic studies in twelve patients with primary myelofibrosis and myeloid metaplasia.

Chromosome studies on bone marrow and/or peripheral blood cells without phytohemagglutinin were performed on 12 patients with primary myelofibrosis with myeloid meta-plasia (PMMM) between 1980 and 1984. Abnormal clones were found in six patients (50%). In five cases the abnormal clone involved the long arm of chromosome #7, two of which also had partial trisomy of chromosome #1 and trisomy of 9. Additional abnormalities involving chromosomes #3, #5, #11, #13, #15, and #21 were each found once. Review of the literature showed few studies on the cytogenetics of PMMM. No specific chromosomal pattern can be established; however, abnormalities described are nonrandom.

Characterisation of a new murine B cell lymphoma.

The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour. The tumour cells show typical B cell characteristics in vitro. These include surface immunoglobulin (Ig) of mu, kappa isotype, surface Ia, Thy-1 negativity and an increased uptake of tritiated thymidine following incubation with lipopolysaccharide. A31 cells secrete low levels of IgM into the tissue culture fluid. Short-term culture produced only 100 ng IgM per 10(7) cells over 8 h and no tumour-associated monoclonal band could be detected in the serum of tumour-bearing mice. Chromosomal karyotypes of A31 cells gave model numbers 2n=40 normal, and 2n=41, with partial trisomy of chromosome 2, and trisomy of 17. There was loss of a chromosome 6 and the Y chromosome, together with the translocation of part of an 11 to one of the two unidentified marker chromosomes. The responses of lymphoma-bearing mice to therapeutic levels of cyclophosphamide and vincristine sulphate and also to whole body X-radiation are illustrated. This tumour may help in unravelling the complex biology of B cell lymphoma and because of its low level of Ig secretion, be of particular value in experimental immunotherapy.

Spontaneous in vitro neoplastic evolution: Recurrent chromosome changes of newly immortalized Chinese hamster cells

Spontaneous neoplastic progression in cultured Chinese hamster cells was studied at the earliest stage possible. Eighteen independent newly immortalized cell populations (from six individual chinese hamsters) were characterized for karyotype instability. Colonies were selected from initial sparse platings of adult or fetal cells and were expanded for study. The chromosomes from these newly established cell lines were studied using a combination of G-banding and flow karyotype analysis. At a slightly later passage, the 18 cell lines were tested for tumorigenicity in nude mice. Frequent recurring chromosome changes were observed in the karyotypes. The most frequent changes were either total or partial trisomy of chromosome #3 (83%) and trisomy of chromosome #5 (61%). Only 4 of 18 clones (22%) were tumorigenic at the time of testing, and these had long latent periods. The presence of recurrent chromosome changes did not obligate these cell lines to become tumorigenic, but the karyotype instability appeared to be an indicator of the ongoing process of neoplasia.

Partial trisomy 1 (q42→ter)

Clinical findings on three closely related, severely malformed infants and a 20-week-old fetus with an identical partial trisomy of chromosome 1 (1q42 leads to ter) have made possible the delineation of a new syndrome. The typical manifestations of this syndrome are: severe intrauterine and postnatal developmental retardation, trigonocephaly with wide sutures and fontanels, characteristic facial features, colobomata of the iris, small hands and feet, and early death.

Two Children with a Partial Trisomy of Chromosome 15 (47,XX,+15)

Two Children with a Partial Trisomy of Chromosome 15 (47,XX,+15)

Gene dosage for isocitrate dehydrogenase in mouse embryos trisomic for chromosome 1

IT is generally assumed that changes in chromosome number are reflected in gene dosage effects for loci located in the extra or missing chromosomes. Although such effects have been well substantiated in Drosophila1 data for mammalian aneuploidy are scarce. Quantitative gene dosage effects have been demonstrated for several X-linked enzymes in oocytes of mice with X-chromosome aneuploidy2,3 and for malic enzyme in mice with partial trisomy of chromosome 7 (ref. 4). In man, similar effects for superoxide dismutase-1 (W. W. Feaster, L. W. Kwok and C.J.E., unpublished and ref. 5), adenine phosphoribosyltransferase6, purine nucleoside phosphorylase7 and erythrocyte acid phosphatase8 have been observed in cells aneuploid for chromosomes 21, 16, 14 and 2, respectively. Aneuploidy for chromosome 21 also affects responsiveness to interferon9, and XYY cells have been claimed to have increased amounts of H–Y surface antigen10. Since the detection of more than 30 metacentric (Robertsonian translocation) chromosomes in wild and laboratory strains11,12 and the development of a mating scheme which utilises such translocations for the production of aneuploid embryos in relatively high frequencies13,14, the mouse has become particularly useful for gene dosage studies. We have used this system to demonstrate the dosage effect for supernatant isocitrate dehydrogenase (Id-1) which results from trisomy for chromosome 1.

A partial trisomy of chromosome 1 in a family with a t(1q-;4q+) translocation.

A female infant with approximately one‐third of the terminal portion of the 1q chromosome arm attached to the end of a 4q arm (46,XX,4q+) is described. The proposita's mother, maternal grandfather and uncle are balanced translocation carriers 46,XX or XY,t(1q‐;4qf). The clinical findings were: elfin‐like facies, low set ears with large pinnae, and numerous cardiac anomalies. The proposita expired at eleven weeks of age.

Identification of partial 12 trisomy by quinacrine fluorescence

A patient whose clinical manifestations suggested a diagnosis of Down's syndrome was shown by conventional chromosome analysis to have a normal karyotype. However, examination by fluorescent stains indicated that he had partial trisomy of chromosome No. 12 and deletion of a small portion of chromosome No. 8. His father and sister carried a reciprocal translocation involving these two chromosomes.

Partial Trisomy-Deficiency Syndrome Resulting from a Reciprocal Translocation in a Large Kindred

Three sibs with similar phenotypic abnormalities were found to have partial trisomy of chromosome 18 and a sizeable deficiency of one of the G chromosomes. The mother and her father as well as five other maternal relatives are carriers of a reciprocal translocation. A total of 35 individuals were tested. Viability in spite of a large deficiency may be explained by the distribution of heterochromatin and euchromatin in the acrocentric chromosome. The recovery of only one combination from adjacent segregation is probably the result of parallel orientation of a chain of four and/or early zygotic lethality. Blood grouping studies showed that the loci for Rh, MN, Duffy and Kidd are not situated on the deleted portion of the G chromosome involved.