A new type of inversion of a human Y chromosome.

Using chromosome banding techniques, a phenotypically normal male was found to have an abnormal banding pattern of the Y chromosome. By the constitutive heterochromatin staining method, a darkly stained band was located on the short arm and the proximal region of the long arm. The quinacrine staining method also showed a similar abnormal banding pattern: a brightly fluorescing band was seen on the short arm and the proximal region of the long arm. By the conventional Giemsa staining method, however, no specific morphological abnormality was detected in the aberrant Y. On detailed karyotype analyses no recognizable abnormality of banding patterns of any other chromosome was found aside from the abnormal Y. The abnormality was determined to be a complex inversion of the Y chromosome, which is described as 46,X,inv(Y)(pter leads to p11::q11 leads to q12::cen::q12 leads to qter).     

An infertile male with balanced Y;19 translocation. Review of Y;autosome translocations.

Cytogenetic studies on a phenotypically normal male, presenting with infertility, revealed a balanced Y;19 translocation - 46,XY,t (Y;19) (q11; p or q13). The patient had a normal hormone profile, but semen analysis showed immature cells in the fluid. The possible mechanisms causing the infertility are discussed. An extensive review of the literature of Y ; autosome translocations indicates that there are 2 types, those in which the broken segment of the Y is translocated to the short arm or centromeric region of an acrocentric chromosome, and those in which the Y material is translocated onto a long or short arm region of a non-acrocentric chromosome. The first type is less frequently associated with infertility and hypogonadism than the second type. There is presumptive evidence that the first type is non-random.     

A new type of inversion of a human Y chromosome

Summary Using chromosome banding techniques, a phenotypically normal male was found to have an abnormal banding pattern of the Y chromosome. By the constitutive heterochromatin staining method, a darkly stained band was located on the short arm and the proximal region of the long arm. The quinacrine staining method also showed a similar abnormal banding pattern: a brightly fluorescing band was seen on the short arm and the proximal region of the long arm. By the conventional Giemsa staining method, however, no specific morphological abnormality was detected in the aberrant Y. On detailed karyotype analyses no recognizable abnormality of banding patterns of any other chromosome was found aside from the abnormal Y. The abnormality was determined to be a complex inversion of the Y chromosome, which is described as 46,X,inv(Y)(pterp11::q11q12::cen::q12qter).     

Mammalian sex chromosomes. II. Pairing and alignment of the X and Y chromosomes of the pygmy mouse, Mus dunni

In the pygmy mouse, Mus dunni, the entire Y chromosome and the short arm of the X and distal region of its long arm are constitutively heterochromatic. Different banding studies on somatic chromosomes revealed the GC nature of the distally located heterochromatin of the long arms of both the X and Y chromosomes. The short arm of the X and the rest of the Y are AT-rich. During meiosis, the long arms of the X and Y paired extensively, sometimes more than half of the Y pairing with the X. This observation is in disagreement with that of Pathak and Hsu (1976) who reported end-to-end pairing between the long arm of the X and the short arm of the Y. The orientation observed by us is favourable to a successful meiotic recombination but whether this takes place remains to be demonstrated.     

A family case of fertile human 45,X,psu dic(15;Y) males

We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family.     

Chondrodysplasia punctata with X;Y translocation

Summary We have studied a family in which the mother and her son were carriers of an X;Y translocation, der(X)t(X;Y) (p22.3;q11). The mother was of slightly short stature and had mildly short upper extremities. The son had epiphyseal punctate calcifications, mildly short extremities, a flattened nasal bridge, and mental retardation (chondrodysplasia punctata). The extra bands on the short arm of the X chromosome were identified as deriving from the long arm of the Y chromosome, using in situ hybridization with a Y-chromosome-specific DNA probe (pHY10). The chondrodysplasia punctata seen in our case may be associated with the abnormality of the distal short arm of the X chromosome caused by X;Y translocation.     

A unique dicentric X;Y translocation with Xq and Yp breakpoints: cytogenetic and molecular studies.

A 32-year-old woman presented with secondary amenorrhea and infertility. She was of normal height and her breasts were well developed, but she had streak gonads; there were no signs of virilization, and she showed no somatic stigmata of Turner syndrome. Chromosome analysis revealed a dicentric X;Y translocation with Xq and Yp breakpoints. Centromeric banding demonstrated a Y centromere and a "suppressed" X centromere. The karyotype of the patient was interpreted as 46,X,t(X;Y)(q22;p11). The Yp breakpoint was confirmed by DNA-hybridization studies with six probes detecting Y-specific sequences. These DNA-hybridization studies were consistent with the presence of the long arm, centromere, and much of the proximal short arm of the Y. The Y-DNA studies of this female also revealed the absence of the distal short arm of the Y chromosome, to which the testis-determining factor has previously been localized.     

Demonstration of two different regions of lateral asymmetry in human Y chromosomes

Summary Two differently stained regions of lateral asymmetry were observed in the long arm of the human Y chromosome, following FPG staining. The first asymmetry was confined to band q12 of the long arm. The second asymmetrically stained region was located at the junction between bands q11 and q12. In the non-fluorescent Y chromosomes only one region of lateral asymmetry was found at the end of the long arm and its staining properties were similar to the region situated at the junction between q11 and q12 bands in the fluorescent Ys. The two morphologically distinguishable regions of lateral asymmetry are presumed to indicate sites containing different satellite DNAs in the human Y chromosome.     

Shared DNA sequences between the X and Y chromosomes in the tammar wallaby – evidence for independent additions to eutherian and marsupial sex chromosomes

Marsupial sex chromosomes are smaller than their eutherian counterparts and are thought to reflect an ancestral mammalian X and Y. The gene content of this original X is represented largely by the long arm of the human X chromosome. Genes on the short arm of the human X are autosomal in marsupials and monotremes, and represent a recent addition to the eutherian X and Y. The marsupial X and Y apparently lack a pseudoautosomal region and show only end-to-end pairing at meiosis. However, the sex chromosomes of macropodid marsupials (kangaroos and wallabies) are larger than the sex chromosomes of other groups, and a nucleolus organizer is present on the X and occasionally the Y. Chromosome painting using DNA from sorted and microdissected wallaby X and Y chromosomes reveals homologous sequences on the tammar X and Y chromosomes, concentrated on the long arm of the Y chromosome and short arm of the X. Ribosomal DNA sequences were detected by fluorescence in situ hybridization on the wallaby Xp but not the Y. Since no chiasmata have been observed in marsupial sex chromosomes, it is unlikely that these shared sequences act as a pseudoautosomal region within which crossing over may occur, but they may be required for end-to-end associations. The shared region of wallaby X and Y chromosomes bears no homology with the recently added region of the eutherian sex chromosomes, so we conclude that independent additions occurred to both sex chromosomes in a eutherian and macropodid ancestor, as predicted by the addition-attrition hypothesis of sex chromosome evolution. Received: 18 October 1996 / Accepted: 21 February 1997     

Translocation (Y;19)(q12;q13) and azoospermia

An azoospermic male with a 46,X,t(Y;19)(q12;q13) karyotype is described. The comparison with 12 similar cases reveals that the Y breakpoints are usually on the long arm whereas the autosomal ones seem to be at random. Since a premeiotic origin is inconsistent with the arrest at diakinesis seen in those cases with meiotic studies, we postulate that a balanced t(Y;A) arises either via a chromatid exchange in the meiotic interphase or through a chromosome exchange in spermiogenesis or at the one cell stage of the zygote.     

Molecular evidence of Y-autosomal translocations in owl monkeys

Probe pDP1007, which contains highly conserved DNA sequences from the sex-determining region of the human Y chromosome, cross-hybridized with owl monkey EcoRI restriction fragments of 1.8 kb and 6.6 kb. Southern transfer analysis of owl monkey (karyotype VI)--rodent somatic cell hybrids localized the 1.8-kb fragment on the owl monkey X chromosome and the 6.6-kb fragment, which is male specific, on chromosome 14/Y. Regional in situ chromosome mapping of pDP1007 revealed specific sites of hybridization: the distal short arm of the X chromosome of karyotypes IV, VI, and VII; the small metacentric Y of karyotype IV; the C-band positive region on the short arm of chromosome 17/Y (karyotype VII); and the C-band positive region on the long arm of chromosome 14/Y (karyotype VI). These molecular findings reinforce cytological evidence that Y-chromosomal material has been transferred to autosomes 14 and 17 in owl monkeys of karyotypes VI and VII, respectively, in which there are no independently segregating Y chromosomes.     

A Y/15 translocation in a 45,X male with Prader-Willi syndrome

We report a male neonate with a 45 X karyotype; the long arm of a chromosome 15 was translocated onto the proximal long arm of the Y chromosome. Breakpoints were identified by in situ fluorescence hybridization (FISH) on the proximal 15q13 and Yq11.2. The derivative chromosome has no primary centromere. Clinical features were compatible with Prader-Willi syndrome. This is the first report case ofmonosomy 15q and Yq deletion with Prader-Willi syndrome.     

Replication pattern of the X and Y chromosomes in partially synchronized human lymphocyte cultures

The replication pattern of the X and Y chromosomes at the beginning of the synthetic phase was studied in human lymphocyte cultures partially synchronized by the addition of 5-fluoro-2-deoxyuridine (FUdR). The data were evaluated statistically by an analysis of the distribution of silver grain counts over the X and Y chromosomes. —In cells from normal females, one of the X chromosomes began replication later than any other chromosomes of the complement. The short arm of the late replicating X chromosome started replication earlier than the long arm. The telomeric region of the short arm was a preferential site of DNA synthesis at the beginning of replication. —In partially synchronized lymphocyte cultures from a patient with the XXY syndrome, the Y chromosome started replication together with the late replicating X chromosome. The Y chromosome most frequently replicated synchronously with the short arm of the X. The centromeric region of the Y chromosome initiated synthesis before the telomeric region and appeared to replicate synchronously with the telomeric region of the short arm of the X. These findings are discussed with reference to the pairing of the X and Y chromosomes at meiosis.Supported in part by the National Institute of Health Research Grant HD-01979 and National Foundation Birth Defects Research Grant CRCS-40. Dr. Knight was a predoctoral fellow under National Institute of Health Training Program HD-00049-09.     

Unusual segregation products in sperm from a pericentric inversion 17 heterozygote

Chromosome segregation and interchromosomal effect were studied in spermatozoa from a carrier of a pericentric chromosome 17 inversion, 46,XY,inv(17)(p13.1q25.3). Sperm chromosome segregation, lymphocytes of the inversion carrier, and cells from his offspring were analysed by multicolour fluorescence in situ hybridization. The frequency of balanced sperm was 73%. An unusual segregation of recombinants was observed, viz. deletion of the p arm (14.6%) or duplication of the p arm with the presence of one q arm (8.4%), instead of the expected recombinants, viz. duplication of one arm with deletion of the other and vice versa. These unusual recombinants were explained by the position of the 17q breakpoint, which was between the q arm telomere-associated repeats and the unique q subtelomere region. The offspring of the donor were found to have a 17p deletion including the Miller-Dieker critical region, similar to the most frequent recombinant sperm class. The disomy frequency was significantly increased for chromosome 17 compared with other autosomes, suggesting that pairing and recombination of the inversion may predispose to non-disjunction. There was no significant difference between the frequencies of aneuploidy for chromosomes 13, 21, X and Y in the chromosome inversion heterozygote compared with controls. Thus, this unique pericentric inversion of chromosome 17 produces unusual recombinant products; no evidence was apparent of an interchromosomal effect in any of the tested chromosomes.     

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

Summary In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites.     

Mapping the SRY gene in Microtus cabrerae: a vole species with multiple SRY copies in males and females.

The SRY gene is a single-copy, male-specific gene, located on the Y chromosome in most mammals. However, recently we have described the presence of multiple polymorphic copies of this gene in both males and females of the vole species Microtus cabrerae. Here, we present the chromosomal localization of SRY gene copies in this species by fluorescent in situ hybridization (FISH). This technique localized these gene copies in the short arm, and hence in the euchromatic region, of the Y chromosome. Furthermore, several copies of the SRY gene are located on the X chromosome. These copies are spread along the entire heterochromatic region of the X chromosome, occupying the whole short arm, the centromeric region, and the pericentromeric region of the long arm.     

Analysis of complex Y chromosome aberrations using a single DNA probe (Y-367)

A specific cloned DNA sequence (Y-367) detects at least four loci in the euchromatic long arm and in the short arm of the human Y chromosome. Deletion mapping assigns one locus to the distal euchromatic long arm, another to a region close to the centromere on either Yq or Yp, and two additional loci to the Y short arm. Y-367 may thus be used for the rapid screening of even complex Y chromosome aberrations. This is exemplified in a 45,X male with Y chromosome material on the long arm of chromosome 10 by the detection of an inversion of a portion of Yp and by the confirmation of duplications and deletions in two individuals with duplications of part of the Y chromosome.     

Meiotic studies in an azoospermic boar carrying a Y;14 translocation

A reciprocal translocation between the q arm of the Y chromosome and the q arm of chromosome 14 was identified in a young, phenotypically normal boar presenting azoospermia. Testicular biopsies were analyzed by classical histological and immunolocalization techniques, and by fluorescence in situ hybridization. Meiotic pairing analysis of 85 pachytene spreads showed the presence of an open structure corresponding to a quadrivalent formed by chromosomes 14, X, and the derivative chromosomes 14 and Y in 84.7% of the cases. In the remaining cases (15.3%), a 'trivalent plus univalent' configuration was observed. Immunolocalization of gammaH2AX revealed the presence of this modified histone in the chromatin domains of unsynapsed segments (centromeric region of chromosome 14) and spreading of the gammaH2AX signal from the XY body throughout chromosome 14 in 7.05% of the cells analyzed. The potential causes of the observed infertility, i.e. activation of meiotic checkpoints and/or silencing of genes necessary for the progression of meiosis, are discussed.     

Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome.

It has been proposed that sequence homology should exist between the short arms of the human sex chromosomes, in the regions pairing at meiosis. Out of 40 clones picked at random from a collection of non-repetitive DNA sequences derived from the human Y chromosome, we have found nine sequences which show very high homology with sequences located on the X chromosome. All nine probes originate from the euchromatic part of the Y chromosome. All the homologous sequences are located within the Xq12-Xq22-24 region. None of them map to the short arm of the X chromosome. We conclude that an important part of the euchromatic region of the Y chromosome is homologous to the middle of the X chromosome long arm, possibly as a result of recent translation event(s).     

The role of the Y-chromosome in sex determination.

The basic plan of gonadal development in both sexes is female unless testes are induced by factor(s) of the Y chromosome, known as testis determining factor(s) (TDF). It is not clearly established whether the Y chromosome control is autonomous or under the control of a gene on the X chromosome or autosomes. A gene for the H-Y antigen (Histocompatibility-Y antigen) has been postulated to be the factor determining testicular differentiation. Recent studies have demonstrated that the gene for testis determination and the H-Y determinant are two separate entities. Although earlier cytogenetic observations localized TDF on the pericentric region of the short arm of the Y chromosome, subsequent findings by high-resolution chromosome banding and molecular analysis localise TDF to the distal part of the short arm of the Y chromosome, adjacent to the pseudoautosomal region. A candidate for TDF, the ZFY, was localised within the 140 kb interval where the position of TDF was defined, and considered as the TDF gene. However, a smaller gene sequence of 35 kb, the SRY, situated outside the 140 kb ZFY region, has recently been isolated and proved to be the only and the smallest part of the Y chromosome necessary for male sex determination.