Normal and abnormal interchanges between the human X and Y chromosomes

A single obligatory recombination event takes place at male meiosis in the tips of the X- and Y-chromosome short arms (i.e. the pseudoautosomal region). The crossover point is at variable locations and thus allows recombination mapping of the pseudoautosomal loci along a gradient of sex linkage. Recombination at male meiosis in the terminal regions of the short arms of the X and Y chromosomes is 10- to 20-fold higher than between the same regions of the X chromosomes during female meiosis. The human pseudoautosomal region is rich in highly polymorphic loci associated with minisatellites. However, these minisatellites are unrelated to those resembling the bacterial Chi sequence and which possibly represent recombination hotspots. The high recombination activity of the pseudoautosomal region at male meiosis sometimes results in unequal crossover which can generate various sex-reversal syndromes.

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Human Spermatogenesis Tolerates Massive Size Reduction of the Pseudoautosomal Region

Genome Biology and Evolution ◽

10.1093/gbe/evaa168 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1961-1964

Author(s):

Maki Fukami ◽

Yasuko Fujisawa ◽

Hiroyuki Ono ◽

Tomoko Jinno ◽

Tsutomu Ogata

Keyword(s):

Animal Studies ◽

Male Meiosis ◽

Size Reduction ◽

Pseudoautosomal Region ◽

Minimal Size ◽

Y Chromosomes ◽

Cytogenetic Analyses ◽

Human Spermatogenesis ◽

Complete Deletion ◽

Chromosomal Recombination

Abstract Mammalian male meiosis requires homologous recombination between the X and Y chromosomes. In humans, such recombination occurs exclusively in the short arm pseudoautosomal region (PAR1) of 2.699 Mb in size. Although it is known that complete deletion of PAR1 causes spermatogenic arrest, no studies have addressed to what extent male meiosis tolerates PAR1 size reduction. Here, we report two families in which PAR1 partial deletions were transmitted from fathers to their offspring. Cytogenetic analyses revealed that a ∼400-kb segment at the centromeric end of PAR1, which accounts for only 14.8% of normal PAR1 and 0.26% and 0.68% of the X and Y chromosomes, respectively, is sufficient to mediate sex chromosomal recombination during spermatogenesis. These results highlight the extreme recombinogenic activity of human PAR1. Our data, in conjunction with previous findings from animal studies, indicate that the minimal size requirement of mammalian PARs to maintain male fertility is fairly small.

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Sex Chromosomes and Psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.153.5.675 ◽

1988 ◽

Vol 153 (5) ◽

pp. 675-683 ◽

Cited By ~ 125

Author(s):

T. J. Crow

Keyword(s):

Sex Chromosomes ◽

Distal Segment ◽

Depressive Illness ◽

Male Meiosis ◽

High Rate ◽

Pseudoautosomal Region ◽

Psychiatric Disease ◽

Same Sex ◽

Y Chromosomes ◽

Gender Influences

Although the incidence of the recurrent psychoses (bipolar affective illness and schizophrenia) in the two sexes is approximately equal, gender influences a number of aspects of major psychiatric disease: unipolar depressive illness is twice as common in females, onset of schizophrenia is earlier and outcome is worse in males, and pairs of psychotic first-degree relatives are more often than expected of the same sex. In addition, sex chromosomal aneuploidies (e.g. XXY and XXX) are more frequent in patients with psychosis. Some of these findings can be explained if there is a major locus of predisposition to psychiatric disease in the ‘pseudoautosomal’ region of the sex chromosomes – that distal segment of the short arms in which there is genetic exchange between X and Y chromosomes at male meiosis. A gene located here would be transmitted in an autosomal manner, but would be passed above chance expectation to children of the same sex when inherited through a male. In that this segment of the sex chromosomes is subject to a high rate of recombination (which could generate new mutations), and may include determinants of brain lateralisation, it appears that the pseudoautosomal region could carry the genes which predispose to the major psychoses.

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Silencing of Unpaired Chromatin and Histone H2A Ubiquitination in Mammalian Meiosis

Molecular and Cellular Biology ◽

10.1128/mcb.25.3.1041-1053.2005 ◽

2005 ◽

Vol 25 (3) ◽

pp. 1041-1053 ◽

Cited By ~ 207

Author(s):

Willy M. Baarends ◽

Evelyne Wassenaar ◽

Roald van der Laan ◽

Jos Hoogerbrugge ◽

Esther Sleddens-Linkels ◽

...

Keyword(s):

Mouse Models ◽

Meiotic Prophase ◽

Transcriptional Silencing ◽

Male Meiosis ◽

Histone H2a ◽

Barr Body ◽

Female Meiosis ◽

Autosomal Region ◽

Y Chromosomes ◽

The Relationship

ABSTRACT During meiotic prophase in male mammals, the X and Y chromosomes are incorporated in the XY body. This heterochromatic body is transcriptionally silenced and marked by increased ubiquitination of histone H2A. This led us to investigate the relationship between histone H2A ubiquitination and chromatin silencing in more detail. First, we found that ubiquitinated H2A also marks the silenced X chromosome of the Barr body in female somatic cells. Next, we studied a possible relationship between H2A ubiquitination, chromatin silencing, and unpaired chromatin in meiotic prophase. The mouse models used carry an unpaired autosomal region in male meiosis or unpaired X and Y chromosomes in female meiosis. We show that ubiquitinated histone H2A is associated with transcriptional silencing of large chromatin regions. This silencing in mammalian meiotic prophase cells concerns unpaired chromatin regions and resembles a phenomenon described for the fungus Neurospora crassa and named meiotic silencing by unpaired DNA.

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Recombination between the X and Y chromosomes and the Sxr region of the mouse

Genetics Research ◽

10.1017/s0016672300030925 ◽

1992 ◽

Vol 60 (3) ◽

pp. 175-184 ◽

Cited By ~ 6

Author(s):

Anne McLaren ◽

Elizabeth Simpson ◽

Colin E. Bishop ◽

Michael J. Mitchell ◽

Susan M. Darling

Keyword(s):

Y Chromosome ◽

X Chromosome ◽

Recombination Frequency ◽

Male Meiosis ◽

Homologous Region ◽

Crossing Over ◽

Female Meiosis ◽

Unequal Crossing Over ◽

Y Chromosomes ◽

Autosome Translocation

SummaryThe Sxr (sex-reversed) region that carries a copy of the mouse Y chromosomal testis-determining gene can be attached to the distal end of either the Y or the X chromosome. During male meiosis, Sxr recombined freely between the X and Y chromosomes, with an estimated recombination frequency not significantly different from 50% in either direction. During female meiosis, Sxr recombined freely between the X chromosome to which it was attached and an X-autosome translocation. A male mouse carrying the original Sxra region on its Y chromosome, and the shorter Sxrb variant on the X, also showed 50% recombination between the sex chromosomes. Evidence of unequal crossing-over between the two Sxr regions was obtained: using five markers deleted from Sxrb, 3 variant Sxr regions were detected in 159 progeny (1·9%). Four other variants (one from the original cross and three from later generations) were presumed to have been derived from illegitimate pairing and crossing-over between Sxrb and the homologous region on the short arm of the Y chromosome. The generation of new variants throws light on the arrangement of gene loci and other markers within the short arm of the mouse Y chromosome.

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The Location of the Pseudoautosomal Boundary in Silene latifolia

Genes ◽

10.3390/genes11060610 ◽

2020 ◽

Vol 11 (6) ◽

pp. 610

Author(s):

Marc Krasovec ◽

Yu Zhang ◽

Dmitry A. Filatov

Keyword(s):

Genetic Map ◽

Sex Chromosomes ◽

Male Meiosis ◽

Silene Latifolia ◽

Pseudoautosomal Region ◽

Wild Populations ◽

Y Chromosomes ◽

Polymorphism Data ◽

Fuzzy Boundary ◽

Over Time

Y-chromosomes contain a non-recombining region (NRY), and in many organisms it was shown that the NRY expanded over time. How and why the NRY expands remains unclear. Young sex chromosomes, where NRY expansion occurred recently or is on-going, offer an opportunity to study the causes of this process. Here, we used the plant Silene latifolia, where sex chromosomes evolved ~11 million years ago, to study the location of the boundary between the NRY and the recombining pseudoautosomal region (PAR). The previous work devoted to the NRY/PAR boundary in S. latifolia was based on a handful of genes with locations approximately known from the genetic map. Here, we report the analysis of 86 pseudoautosomal and sex-linked genes adjacent to the S. latifolia NRY/PAR boundary to establish the location of the boundary more precisely. We take advantage of the dense genetic map and polymorphism data from wild populations to identify 20 partially sex-linked genes located in the “fuzzy boundary”, that rarely recombines in male meiosis. Genes proximal to this fuzzy boundary show no evidence of recombination in males, while the genes distal to this partially-sex-linked region are actively recombining in males. Our results provide a more accurate location for the PAR boundary in S. latifolia, which will help to elucidate the causes of PAR boundary shifts leading to NRY expansion over time.

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UNEQUAL CROSSING OVER AT THE rRNA TANDON AS A SOURCE OF QUANTITATIVE GENETIC VARIATION IN DROSOPHILA

Genetics ◽

10.1093/genetics/95.3.727 ◽

1980 ◽

Vol 95 (3) ◽

pp. 727-742 ◽

Cited By ~ 1

Author(s):

R Frankham ◽

D A Briscoe ◽

R K Nurthen

Keyword(s):

Genetic Variation ◽

Selection Response ◽

Crossing Over ◽

Wild Type ◽

X Chromosomes ◽

Unequal Crossing Over ◽

Quantitative Genetic ◽

Y Chromosomes ◽

Homozygous Line ◽

Minimum Estimate

ABSTRACT Abdominal bristle selection lines (three high and three low) and controls were founded from a marked homozygous line to measure the contribution of sex-linked "mutations" to selection response. Two of the low lines exhibited a period of rapid response to selection in females, but not in males. There were corresponding changes in female variance, in heritabilities in females, in the sex ratio (a deficiency of females) and in fitness, as well as the appearance of a mutant phenotype in females of one line. All of these changes were due to bb alleles (partial deficiencies for the rRNA tandon) in the X chromosomes of these lines, while the Y chromosomes remained wild-type bb+. We argue that the bb alleles arose by unequal crossing over in the rRNA tandon.—A prediction of this hypothesis is that further changes can occur in the rRNA tandon as selection is continued. This has now been shown to occur.—Our minimum estimate of the rate of occurrence of changes at the rRNA tandon is 3 × 10-4. As this is substantially higher than conventional mutation rates, the questions of the mechanisms and rates of origin of new quantitative genetic variation require careful re-examination.

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The Continuum of Psychosis and Its Genetic Origins

The British Journal of Psychiatry ◽

10.1192/bjp.156.6.788 ◽

1990 ◽

Vol 156 (6) ◽

pp. 788-797 ◽

Cited By ~ 187

Author(s):

T. J. Crow

Keyword(s):

Sex Chromosome ◽

Homo Sapiens ◽

Polymorphic Marker ◽

Cerebral Dominance ◽

Homo Erectus ◽

Evolutionary Development ◽

Pseudoautosomal Region ◽

Sibling Pairs ◽

Homo Habilis ◽

Y Chromosomes

Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A post-mortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggests that the gene for psychosis is the ‘cerebral dominance gene‘, the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short-arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition fromAustralopithecusthroughHomo habilisandHomo erectustoHomo sapiens.

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ERRORS IN THE ELIMINATION OF X CHROMOSOMES IN SCIARA OCELLARIS

Genetics ◽

10.1093/genetics/94.3.663 ◽

1980 ◽

Vol 94 (3) ◽

pp. 663-673 ◽

Cited By ~ 2

Author(s):

Lyria Mori ◽

A L P Perondini

Keyword(s):

X Chromosome ◽

Chromosome Elimination ◽

Male Meiosis ◽

Early Embryogenesis ◽

Maternal Influence ◽

Recessive Mutation ◽

X Chromosomes ◽

Heterozygous Condition ◽

Selective Elimination

ABSTRACT It was previously assumed that the X-linked recessive mutation, sepia, induced errors in X-chromosome elimination during early embryogenesis of Sciam ocellaris. The results obtained in the present analysis corroborate this assumption and permit a further classification of the type of error this mutation induces. Among 85,244individuals analyzed, three kinds of aberrant flies were identified: mosaics (0.01 %), gynandromorphs (0.42%)and phenotypically exceptional individuals (0.25%).The origin ofthese abnormal flies could be ascribed to errors in selective elimination of X chromosomes that occur in male meiosis or during the early cleavages of the zygote nuclei. This last kind of error could be classified into three types: (a) error in number, (b) error in type, and (c) error in number and type of X chromosome eliminated. Evidence is provided indicating that sepia has no direct effect on the X chromosome; it has a maternal influence and exerts its effect only in the heterozygous condition.

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DIFFERENTIAL DNA REPLICATION IN THE XX AND XY CELLS OF MUSCA DOMESTICA L. OCRA STRAIN

Canadian Journal of Genetics and Cytology ◽

10.1139/g70-065 ◽

1970 ◽

Vol 12 (3) ◽

pp. 461-473 ◽

Cited By ~ 2

Author(s):

K. Y. Jan ◽

J. W. Boyes

Keyword(s):

Dna Replication ◽

Musca Domestica ◽

Sex Chromosomes ◽

Chromosome Length ◽

Final Part ◽

X Chromosomes ◽

Y Chromosomes ◽

Heteromorphic Sex Chromosomes ◽

Autosomal Pair ◽

Differential Dna Replication

The karyotype of Musca domestica L. ocra strain, consists of the sex chromosomes and five autosomal pairs. The heteromorphic sex chromosomes are heterochromatic and mitotically unpaired, whereas the autosomes are euchromatic and mitotically paired. All autosomal pairs and both X and Y chromosomes are cytologically recognizable.The relative labelling rate, R (in terms of the number of grains counted per 100 labelled metaphases per μ of chromosome length) for the sex chromosomes and for each autosomal pair was followed from 1.5 hours to 8 hours after H3TdR injection. The pattern of labelling rate was similar for the different autosomal pairs in the XX cells but this pattern for the autosomal pairs in the XY cells, though also similar for the different pairs, differed appreciably from that found in the XX cells. The pattern of the labelling rate for the X chromosomes was similar in the XX and XY cells. Also the pattern of labelling rate for the X and Y chromosomes was similar during the final part of the replication period. The two X chromosomes in the XX cells and the X and Y chromosomes in the XY cells completed labelling later than the autosomes.

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Xist imprinting is promoted by the hemizygous (unpaired) state in the male germ line

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1519528112 ◽

2015 ◽

Vol 112 (47) ◽

pp. 14415-14422 ◽

Cited By ~ 13

Author(s):

Sha Sun ◽

Bernhard Payer ◽

Satoshi Namekawa ◽

Jee Young An ◽

William Press ◽

...

Keyword(s):

X Chromosome ◽

Germ Line ◽

Transgenic Animals ◽

Early Embryo ◽

Male Meiosis ◽

Meiotic Pairing ◽

Male Germ Line ◽

Specific Expression ◽

X Chromosomes ◽

High Level

The long noncoding X-inactivation–specific transcript (Xist gene) is responsible for mammalian X-chromosome dosage compensation between the sexes, the process by which one of the two X chromosomes is inactivated in the female soma. Xist is essential for both the random and imprinted forms of X-chromosome inactivation. In the imprinted form, Xist is paternally marked to be expressed in female embryos. To investigate the mechanism of Xist imprinting, we introduce Xist transgenes (Tg) into the male germ line. Although ectopic high-level Xist expression on autosomes can be compatible with viability, transgenic animals demonstrate reduced fitness, subfertility, defective meiotic pairing, and other germ-cell abnormalities. In the progeny, paternal-specific expression is recapitulated by the 200-kb Xist Tg. However, Xist imprinting occurs efficiently only when it is in an unpaired or unpartnered state during male meiosis. When transmitted from a hemizygous father (+/Tg), the Xist Tg demonstrates paternal-specific expression in the early embryo. When transmitted by a homozygous father (Tg/Tg), the Tg fails to show imprinted expression. Thus, Xist imprinting is directed by sequences within a 200-kb X-linked region, and the hemizygous (unpaired) state of the Xist region promotes its imprinting in the male germ line.

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