Satellited Y chromosome (Yqs) and nucleolar organizer occurring de novo]

A satellited Y chromosome (Yqs) occurred de novo in a boy born to first cousins. The child had severe mental retardation, facial dysmorphism, congenital heart disease, and amaurosis, and died at 6 months and of age. The chromosome rearrangement was confirmed by R-, G-, C-, Q-, and Ag-NOR banding. Its significance and the difficulty of genetic counseling are discussed.     

A de novo satellited short arm of the Y chromosome possibly resulting from an unstable translocation

A satellited long arm of the Y chromosome (Yqs) is considered a normal variation, whereas the presence of a satellite on the short arm of the Y (Yps) has never been described in the literature. A Yps chromosome could be clinically significant if the translocation resulting in Yps has relocated the testis-determining gene, SRY, to another chromosome. A carrier of such a translocation would therefore be at increased risk for having XX male and XY female offspring. Here we describe the first reported case of de novo Yps present in a phenotypically normal male. This Yps chromosome was positive for C-banding and nucleolus organizer region (NOR) staining and showed a hybridization signal for the -satellite sequence. Fluorescence in situ hybridization (FISH) analysis indicated that SRY was retained on the Yps and the translocation breakpoint on Yps was distal to the pseudoautosomal region. At prenatal diagnosis, a normal appearing Y chromosome was found in his son, and thus the satellite on Yps was lost during meiotic Xp-Yp pairing. This Yps chromosome was likely the product of an unstable translocation.     

The hairy ears (Eh) mutation is closely associated with a chromosomal rearrangement in mouse chromosome 15

The mouse mutation hairy ears (Eh) originated in a neutron irradiation experiment at Oak Ridge National Laboratory. Subsequent linkage studies with Eh and other loci on Chr 15 suggested that it is associated with a chromosomal rearrangement that inhibits recombination since it shows tight linkage with several loci occupying the region extending from congenital goiter (cog) distal to caracul (Ca). We report here (1) linkage experiments confirming this effect on recombination and (2) meiotic and mitotic cytological studies that confirm the presence of a chromosomal rearrangement. The data are consistent with the hypothesis of a paracentric inversion in the distal half of Chr 15. The effect of the inversion extends over a minimum of 30 cM, taking into account the genetic data and the cytologically determined chromosomal involvement extending to the region of the telomere.     

An XXY mouse, the result of a rearrangement between one X and a Y chromosome

A male mouse with irregular white spotting, typical of piebald, s, arose during an experiment designed to search for mutations induced in spermatogonial cells by ethylnitrosourea (ENU). On being examined cytologically it was found to carry 40 chromosomes but was effectively XXY since one of the two X chromosomes present was distally fused to a Y chromosome. In common with the previously described XXY mice, all of which carried 41 chromosomes, the mouse was sterile with a total absence of germ cells. Because of this, it was not possible to determine if the white spotting was inherited. The spotting could not be related to any observable abnormality of chromosomes known to carry spotting genes, nor could it be linked in any way with the X and Y fusion. It was concluded from the cytological considerations and the time interval (6 months) that had elapsed between mutagen treatment and birth of the offspring, that whereas the spotting was probably the result of ENU damage in a spermatogonial stem cell, the XY fusion was probably a later and spontaneous event.     

Familial translocation 22/Y and partial autosomal trisomy in a young girl

Report on a translocation t(22;Y)(q12;p 13) with conservation of the NOR in normal members from 2 generations of a family. The proposita has in addition a small autosomal duplication, probably (1)(q44-ter) which could explain her mental deficiency.     

Silver stain reveals nucleolus organizer regions on a satellited Yq chromosome

Summary Chromosomes from a patient with a satellited Yq were stained with a silver procedure that differentially stains nucleolus organizer regions. The Yqs stained heavily in all cells examined, indicating the presence of ribosomal cistrons at this region. The Yqs also entered into satellite associations with the D and G group chromosomes at a frequency greater than would be expected through chance.     

Quinacrine mustard fluorescence of a second Y chromosome in a Y-autosomal translocation

Summary Screening buccal smears from 97 prisoners by the quinacrine mustard technique revealed one XYY-individual and one Y-autosomal translocation of a second Y chromosome with a 46,XY, D-,t (?15q;Yq)+ karyotype. The translocation chromosome could be identified by its intense fluorescence of the short arm in all 75 metaphases examined.

---

Zusammenfassung Untersuchungen von Abstrichen der Mundschleimhaut von 97 Gefängnisinsassen mit der Quinacrine-Mustard-Methode führten zur Aufdeckung eines XYY-Karyotyps und einer Y-autosomalen Translokation eines zweiten Y-Chromosoms mit einem Karyotyp von 46,XY,D-,t(?15q;Yq)+. Das Translokationschromosom konnte durch helle Fluorescenz des kurzen Armes in allen 75 Metaphasen identifiziert werden.

---

---

This work was supported in part by grant number Pa 118/8 from the Deutsche Forschungsgemeinschaft and is part of a thesis by S. F.     

Centromeric inactivation in a dicentric human Y;21 translocation chromosome

A de novo dicentric Y;21 (q11.23;p11) translocation chromosome with one of its two centromeres inactive has provided the opportunity to study the relationship between centromeric inactivation, the organization of alphoid satellite DNA and the distribution of CENP-C. The proband, a male with minor features of Down’s syndrome, had a major cell line with 45 chromosomes including a single copy of the translocation chromosome, and a minor one with 46 chromosomes including two copies of the translocation chromosome and hence effectively trisomic for the long arm of chromosome 21. Centromeric activity as defined by the primary constriction was variable: in most cells with a single copy of the Y;21 chromosome, the Y centromere was inactive. In the cells with two copies, one copy had an active Y centromere (chromosome 21 centromere inactive) and the other had an inactive Y centromere (chromosome 21 centromere active). Three different partial deletions of the Y alphoid array were found in skin fibroblasts and one of these was also present in blood. Clones of single cell origin from fibroblast cultures were analysed both for their primary constriction and to characterise their alphoid array. The results indicate that (1) each clone showed a fixed pattern of centromeric activity; (2) the alphoid array size was stable within a clone; and (3) inactivation of the Y centromere was associated with both full-sized and deleted alphoid arrays. Selected clones were analysed with antibodies to CENP-C, and staining was undetectable at both intact and deleted arrays of the inactive Y centromeres. Thus centromeric inactivation appears to be largely an epigenetic event. Received: 30 January 1997; in revised form: 3 April 1997 / Accepted: 8 May 1997     

A possible new type of chromosome rearrangement: telomere-centromere translocation (tct) followed by double duplication

Summary The reassessment of a case of complex interchromosomal rearrangement after breakage at centromeric and telomeric regions, and the comparison with four other independently published cases suggested the existence of a new type of rearrangement. It would consist of: formation of an isochromosome after breakage at a centromeric region, duplication of the telomeric region of another chromosome, and reassociation of the nonduplicated arm of the first chromosome with the duplicated telomeric region of the second chromosome.     

Prenatal diagnosis of a de novo satellited chromosome 18 (18ps) associated with 18p deletion

De novo satellited non-acrocentric chromosomes are very rare findings in prenatal diagnosis. Here we report the first case of a de novo 18ps, associated with del(18p), detected at prenatal diagnosis. A 37 years old woman underwent Chorionic Villus Sampling (CVS) for advanced maternal age. Cytogenetic analysis on direct CVS preparation (CVSc) revealed a male karyotype with a nonfamilial satellited 18ps and a reciprocal translocation t(17;19)(P11.1;q11) of maternal origin. The mesenchimal CVS culture (CVSm) showed a mosaic of cell lines with various involvement of chromosome 18: 18ps [36/70]/ r(18) [25/70]/ del(18p) [3/70]/ -18 [6/70]. Amniotic fluid cells (AFC) confirmed the homogeneous karyotype found at CVSc. The molecular cytogenetic characterization, performed on AFC, allowed the following diagnosis: 46,XY, +15, dic(15;18)(p11.1;p11.2), t(17;19)(p11.1;q11)mat. ish dic(15;18)(tel 18p-, D15Z1+, wcp18-, wcp 18+, D18Z1+, tel 18q+). The foetal autopsy disclosed subtle facial dysmorphisms and corpus callosum hypoplasia. In case of prenatal detection of de novo terminal ectopic NORs an accurate cytogenetic and molecular analysis should be performed in order to rule out subtle unbalancements.     

Characterization of a (Y;4) translocation by DNA hybridization

Summary A phenotypically normal male with azoospermia was found to have a translocation between the short arm of the Y chromosome and the distal long arm of a chromosome 4. By cytogenetic analysis it could not be determined whether the translocation was reciprocal, nor whether it was balanced. In situ DNA hybridization with two pseudoautosomal and one Y-specific probe demonstrated that the breakpoint was on distal Yp and that there was Y chromosome material on 4q. Thus the translocation was reciprocal and could be characterized as t(Y;4)(pll;q32). There was no evidence for loss of Y-DNA sequences as judged by Southern blotting with Y-DNA probes. Thus the translocation may be balanced. We conclude that DNA hybridization can be used to refine considerably the cytogenetic analysis of such translocations.     

Clinical consequences of a human non-fluorescent Y chromosome (Ynf)

A new case of ambiguous genitalia and immature tissue in the left gonad is presented. Cytogenetic findings with various techniques demonstrated that the distal two-thirds of the long arm of the Y chromosome is deleted. Q-banding showed a non-fluorescent Y; three positive bands were however noted when the DA/DAPI technique was applied. After a review of the literature, it was concluded that the non-fluorescent Y chromosome (Ynf) when inherited from generation to generation is a heteromorphism in normal males. However, in our case, where the proband's Y is lacking the fluorescent segment, a simple deletion does not appear to adequately explain the DA/DAPI positive bands. Possibly, a deletion followed by a structural rearrangement of the non-fluorescent segment had occurred de novo. The highly Y-specific DNA sequences present in the fluorescent segment are absent in these patients. The abnormal development in these cases is due to the presence of the 45,X cell line. The gene responsible for spermatogenesis has been localized to the non-fluorescent region in the long arm of the Y chromosome. Furthermore, it is concluded that two types of non-fluorescent Y chromosomes can be found in the population; one is a normal inherent heteromorphic variant, while the other appears to be an abnormality, especially in cases with azoospermia. Such distinctions should clearly be established prior to genetic counseling for patients with so called Ynf or del (Yd).     

The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region.

Cytological analysis of the mouse Y* chromosome revealed a complex rearrangement involving acquisition of a functional centromere and centromeric heterochromatin and attachment of this chromosomal segment to the distal end of a normal Y* chromosome. This rearrangement positioned the Y* short-arm region at the distal end of the Y* chromosome and the pseudoautosomal region interstitially, just distal to the newly acquired centromere. In addition, the majority of the pseudoautosomal region was inverted. Recombination between the X and the Y* chromosomes generates two new sex chromosomes: (1) a large chromosome comprised of the X chromosome attached at its distal end to all of the Y* chromosome but missing the centromeric region (XY*) and (2) a small chromosome containing the centromeric portion of the Y* chromosome attached to G-band-negative material from the X chromosome (YX). Mice that inherit the XY* chromosome develop as sterile males, whereas mice that inherit the Y*X chromosome develop as fertile females. Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete spermatogenesis and form functional sperm.     

Heteromorphic sex chromosome system with an exceptionally large Y chromosome in a catfish Steindachneridion sp. (Pimelodidae)

The chromosomes and banding patterns of Steindachneridion sp., a large catfish (Pimelodidae), endemic to the Igua?u River, Brazil, were analyzed using conventional (C-, G-banding) and restriction enzyme banding methods. The same diploid number (2n = 56) as in other members of the genus and the family was found but the karyotype displayed an XX/XY sex chromosome system. The X chromosome was the smallest submetacentric, while the Y was the largest chromosome in the karyotype. Meiotic analysis showed 27 autosomal bivalents plus one heteromorphic XY bivalent during spermatogenesis. Sex chromosomes had no particular pattern after C-banding but G- and restriction enzyme bandings showed specific banding characteristics. The present finding represents the first report of a well-differentiated and uncommon sex chromosome system in the catfish family Pimelodidae.