Investigation by Linkage Analysis of the XY Pseudoautosomal Region in the Genetic Susceptibility to Schizophrenia

1995 ◽  
Vol 167 (3) ◽  
pp. 390-393 ◽  
Author(s):  
Gursharan Kalsi ◽  
David Curtis ◽  
Jon Brynjolfsson ◽  
Robert Butler ◽  
Tonmoy Sharma ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Pseudoautosomal Region ◽  
Lod Score ◽  
Negative Results ◽  
Conflicting Evidence ◽  
Nearby Region ◽  
Affected Sib Pairs ◽  
Sex Chromosome Aneuploidies

BackgroundA susceptibility locus for schizophrenia in the pseudoautosomal region has been proposed on the basis of a possible excess of sex chromosome aneuploidies among patients with schizophrenia and an increased sex concordance in affected sib pairs. Several studies investigating this hypothesis have produced conflicting evidence.MethodIn a series of Icelandic and British families, we used lod score and sib pair linkage analyses with markers for the MIC2 and DXYS14 loci on the pseudoautosomal XY region.ResultsLod and sib pair linkage analysis with these markers produced strongly negative scores. Heterogeneity testing also produced negative results.ConclusionWe conclude that the present study provides no support for the involvement of either the pseudoautosomal region or the nearby region of the sex chromosomes in the aetiology of schizophrenia.

scholarly journals The Eutherian Pseudoautosomal Region

2015 ◽  
Vol 147 (2-3) ◽  
pp. 81-94 ◽  
Author(s):  
Terje Raudsepp ◽  
Bhanu P. Chowdhary
Keyword(s):  
Sex Chromosomes ◽  
Sequence Homology ◽  
Sex Chromosome ◽  
Gene Content ◽  
Pseudoautosomal Region ◽  
Individual Species ◽  
Evolutionary Genetic ◽  
Murid Rodents ◽  
Nucleotide Divergence ◽  
Sex Chromosome Aneuploidies

The pseudoautosomal region (PAR) is a unique segment of sequence homology between differentiated sex chromosomes where recombination occurs during meiosis. Molecular and functional properties of the PAR are distinctive from the autosomes and the remaining regions of the sex chromosomes. These include a higher rate of recombination than genome average, bias towards GC-substitutions and increased interindividual nucleotide divergence and mutations. As yet, the PAR has been physically demarcated in only 28 eutherian species representing 6 mammalian orders. Murid rodents have the smallest, gene-poorest and most diverged PARs. Other eutherian PARs are largely homologous but differ in size and gene content, being the smallest in equids and human/simian primates and much larger in other eutherians. Because pseudoautosomal genes escape X inactivation, their dosage changes with sex chromosome aneuploidies, whereas phenotypic effects of the latter depend on the size and gene content of the PAR. Thus, X monosomy is more viable in mice, humans and horses than in species with larger PARs. Presently, little is known about the functions of PAR genes in individual species, though human studies suggest their involvement in early embryonic development. The PAR is, thus, of evolutionary, genetic and biomedical significance and a ‘research hotspot' in eutherian genomes.

scholarly journals Meiotic Behavior of Achiasmate Sex Chromosomes in the African Pygmy Mouse Mus mattheyi Offers New Insights into the Evolution of Sex Chromosome Pairing and Segregation in Mammals

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1434
Author(s):  
Ana Gil-Fernández ◽  
Marta Ribagorda ◽  
Marta Martín-Ruiz ◽  
Pablo López-Jiménez ◽  
Tamara Laguna ◽  
...  
Keyword(s):  
Dna Repair ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Mammalian Species ◽  
Evolutionary Process ◽  
Small Region ◽  
Pseudoautosomal Region ◽  
Evolution Of Sex ◽  
African Pygmy Mouse

X and Y chromosomes in mammals are different in size and gene content due to an evolutionary process of differentiation and degeneration of the Y chromosome. Nevertheless, these chromosomes usually share a small region of homology, the pseudoautosomal region (PAR), which allows them to perform a partial synapsis and undergo reciprocal recombination during meiosis, which ensures their segregation. However, in some mammalian species the PAR has been lost, which challenges the pairing and segregation of sex chromosomes in meiosis. The African pygmy mouse Mus mattheyi shows completely differentiated sex chromosomes, representing an uncommon evolutionary situation among mouse species. We have performed a detailed analysis of the location of proteins involved in synaptonemal complex assembly (SYCP3), recombination (RPA, RAD51 and MLH1) and sex chromosome inactivation (γH2AX) in this species. We found that neither synapsis nor chiasmata are found between sex chromosomes and their pairing is notably delayed compared to autosomes. Interestingly, the Y chromosome only incorporates RPA and RAD51 in a reduced fraction of spermatocytes, indicating a particular DNA repair dynamic on this chromosome. The analysis of segregation revealed that sex chromosomes are associated until metaphase-I just by a chromatin contact. Unexpectedly, both sex chromosomes remain labelled with γH2AX during first meiotic division. This chromatin contact is probably enough to maintain sex chromosome association up to anaphase-I and, therefore, could be relevant to ensure their reductional segregation. The results presented suggest that the regulation of both DNA repair and epigenetic modifications in the sex chromosomes can have a great impact on the divergence of sex chromosomes and their proper transmission, widening our understanding on the relationship between meiosis and the evolution of sex chromosomes in mammals.

Pseudoautosomal region in schizophrenia: Linkage analysis of seven loci by sib-pair and lod-score methods

1994 ◽  
Vol 52 (2) ◽  
pp. 135-147 ◽  
Author(s):  
Thierry d'Amato ◽  
Gilles Waksman ◽  
Maria Martinez ◽  
Claudine Laurent ◽  
Philip Gorwood ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Pseudoautosomal Region ◽  
Lod Score

scholarly journals Homomorphic ZW chromosomes 1 in a wild strawberry show distinctive recombination heterogeneity but a small sex-determining region

2015 ◽  
Author(s):  
Jacob A Tennessen ◽  
Rajanikanth Govindarajulu ◽  
Aaron Liston ◽  
Tia-Lynn Ashman
Keyword(s):  
Sex Chromosomes ◽  
Recombination Rate ◽  
Sex Chromosome ◽  
Pseudoautosomal Region ◽  
List Type ◽  
Recombination Suppression ◽  
Female Function ◽  
Wild Strawberry ◽  
Plant Sex Chromosomes ◽  
Recombination Dynamics

SummaryRecombination in ancient, heteromorphic sex chromosomes is typically suppressed at the sex-determining region (SDR) and proportionally elevated in the pseudoautosomal region (PAR). However, little is known about recombination dynamics of young, homomorphic plant sex chromosomes.We examine male and female function in crosses and unrelated samples of the dioecious octoploid strawberry Fragaria chiloensis in order to map the small and recently evolved SDR controlling both traits and to examine recombination patterns on the incipient ZW chromosome.The SDR of this ZW system is located within a 280kb window, in which the maternal recombination rate is lower than the paternal. In contrast to the SDR, the maternal PAR recombination rate is much higher than the rates of the paternal PAR or autosomes, culminating in an elevated chromosome-wide rate. W-specific divergence is elevated within the SDR and a single polymorphism is observed in high species-wide linkage disequilibrium with sex.Selection for recombination suppression within the small SDR may be weak, but fluctuating sex ratios could favor elevated recombination in the PAR to remove deleterious mutations on the W. The recombination dynamics of this nascent sex chromosome with a modestly diverged SDR may be typical of other dioecious plants.

scholarly journals Evolutionary stasis of the pseudoautosomal boundary in strepsirrhine primates

2018 ◽  
Author(s):  
Rylan Shearn ◽  
Alison E. Wright ◽  
Sylvain Mousset ◽  
Corinne Régis ◽  
Simon Penel ◽  
...  
Keyword(s):  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Relative Size ◽  
Pseudoautosomal Region ◽  
Recombination Suppression ◽  
Males And Females ◽  
Work Supports ◽  
Y Degeneration ◽  
Female Genome ◽  
Pseudoautosomal Boundary

AbstractSex chromosomes are typically comprised of a non-recombining region and a recombining pseudoautosomal region. Accurately quantifying the relative size of these regions is critical for sex chromosome biology both from a functional (i.e. number of sex-linked genes) and evolutionary perspective (i.e. extent of Y degeneration and X-Y heteromorphy). The evolution of the pseudoautosomal boundary (PAB) - the limit between the recombining and the non-recombining regions of the sex chromosomes - is well documented in haplorrhines (apes and monkeys) but not in strepsirrhines (lemurs and lorises), which represent almost 30% of all primates. Here we studied the PAB of seven species representing the main strepsirrhine lineages by sequencing a male and a female genome in each species and using sex differences in coverage to identify the PAB. We found that during primate evolution, the PAB has remained unchanged in strepsirrhines whereas several recombination suppression events moved the PAB and shortened the pseudoautosomal region in haplorrhines. Strepsirrhines are well known to have much lower sexual dimorphism than haplorrhines. We suggest that mutations with antagonistic effects between males and females have driven recombination suppression and PAB evolution in haplorrhines. Our work supports the view that sexually antagonistic mutations have influenced the evolution of sex chromosomes in primates.

Evidence for a Pseudo-autosomal Locus for Schizophrenia Using the Method of Affected Sibling Pairs

1991 ◽  
Vol 158 (5) ◽  
pp. 624-629 ◽  
Author(s):  
J. Collinge ◽  
L. E. Delisi ◽  
A. Boccio ◽  
E. C. Johnstone ◽  
A. Lane ◽  
...  
Keyword(s):  
Genetic Linkage ◽  
Sex Chromosome ◽  
Sibling Pairs ◽  
Autosomal Region ◽  
Affected Sibling ◽  
Opposite Sex ◽  
Affected Sib Pairs ◽  
Shared Alleles ◽  
Sex Chromosome Aneuploidies ◽  
Sib Pairs

A susceptibility locus for schizophrenia in the ‘pseudo-autosomal’ region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia.

scholarly journals A Hypothesis: Linking Phase Separation to Meiotic Sex Chromosome Inactivation and Sex-Body Formation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yiding Xu ◽  
Huanyu Qiao
Keyword(s):  
Phase Separation ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Inactivation ◽  
Pseudoautosomal Region ◽  
Future Research ◽  
Homologous Region ◽  
Body Formation ◽  
Meiotic Sex Chromosome Inactivation ◽  
Sex Chromosome Inactivation

During meiotic prophase I, X and Y chromosomes in mammalian spermatocytes only stably pair at a small homologous region called the pseudoautosomal region (PAR). However, the rest of the sex chromosomes remain largely unsynapsed. The extensive asynapsis triggers transcriptional silencing - meiotic sex chromosome inactivation (MSCI). Along with MSCI, a special nuclear territory, sex body or XY body, forms. In the early steps of MSCI, DNA damage response (DDR) factors, such as BRCA1, ATR, and γH2AX, function as sensors and effectors of the silencing signals. Downstream canonical repressive histone modifications, including methylation, acetylation, ubiquitylation, and SUMOylation, are responsible for the transcriptional repression of the sex chromosomes. Nevertheless, mechanisms of the sex-body formation remain unclear. Liquid-liquid phase separation (LLPS) may drive the formation of several chromatin subcompartments, such as pericentric heterochromatin, nucleoli, inactive X chromosomes. Although several proteins involved in phase separation are found in the sex bodies, when and whether these proteins exert functions in the sex-body formation and MSCI is still unknown. Here, we reviewed recent publications on the mechanisms of MSCI and LLPS, pointed out the potential link between LLPS and the formation of sex bodies, and discussed its implications for future research.

scholarly journals Identifying sex-linked markers in Litoria aurea: a novel approach to understanding sex chromosome evolution in an amphibian

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jarrod Sopniewski ◽  
Foyez Shams ◽  
Benjamin C. Scheele ◽  
Ben J. Kefford ◽  
Tariq Ezaz
Keyword(s):  
Sex Determination ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Chromosome Evolution ◽  
Sex Chromosome ◽  
Pseudoautosomal Region ◽  
Nucleotide Polymorphisms ◽  
Sex Chromosome Evolution ◽  
Litoria Aurea ◽  
Novel Approach

Abstract Few taxa exhibit the variability of sex-determining modes as amphibians. However, due to the presence of homomorphic sex chromosomes in many species, this phenomenon has been difficult to study. The Australian frog, Litoria aurea, has been relatively well studied over the past 20 years due to widespread declines largely attributable to chytrid fungus. However, it has been subject to few molecular studies and its mode of sex determination remained unknown. We applied DArTseq™ to develop sex-linked single nucleotide polymorphisms (SNPs) and restriction fragment presence/absence (PA) markers in 44 phenotypically sexed L. aurea individuals from the Molonglo River in NSW, Australia. We conclusively identified a male heterogametic (XX-XY) sex determination mode in this species, identifying 11 perfectly sex-linked SNP and six strongly sex-linked PA markers. We identified a further 47 moderately sex-linked SNP loci, likely serving as evidence indicative of XY recombination. Furthermore, within these 47 loci, a group of nine males were found to have a feminised Y chromosome that significantly differed to all other males. We postulate ancestral sex-reversal as a means for the evolution of this now pseudoautosomal region on the Y chromosome. Our findings present new evidence for the ‘fountain of youth’ hypothesis for the retention of homomorphic sex chromosomes in amphibians and describe a novel approach for the study of sex chromosome evolution in amphibia.

Heteromorphism of “Homomorphic” Sex Chromosomes in Two Anole Species (Squamata, Dactyloidae) Revealed by Synaptonemal Complex Analysis

2017 ◽  
Vol 151 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Artem P. Lisachov ◽  
Vladimir A. Trifonov ◽  
Massimo Giovannotti ◽  
Malcolm A. Ferguson-Smith ◽  
Pavel M. Borodin
Keyword(s):  
Sex Chromosomes ◽  
Complex Analysis ◽  
Sex Chromosome ◽  
Meiotic Chromosome ◽  
Fluorescent Microscopy ◽  
Chromosome Analysis ◽  
Pseudoautosomal Region ◽  
Metaphase Chromosomes ◽  
Recombination Nodules ◽  
Surface Spread

Iguanians (Pleurodonta) are one of the reptile lineages that, like birds and mammals, have sex chromosomes of ancient origin. In most iguanians these are microchromosomes, making a distinction between the X and Y as well as between homeologous sex chromosomes in other species difficult. Meiotic chromosome analysis may be used to elucidate their differentiation, because meiotic prophase chromosomes are longer and less condensed than metaphase chromosomes, and the homologues are paired with each other, revealing minor heteromorphisms. Using electron and fluorescent microscopy of surface spread synaptonemal complexes (SCs) and immunolocalization of the proteins of the SC (SYCP3), the centromere, and recombination nodules (MLH1), we examined sex chromosome synapsis and recombination in 2 species of anoles (Dactyloidae), Anolis carolinensis and Deiroptyx coelestinus, in which the sex chromosomes represent the ancestral condition of iguanians. We detected clear differences in size between the anole X and Y microchromosomes and found an interspecies difference in the localization of the pseudoautosomal region. Our results show that the apparent homomorphy of certain reptile sex chromosome systems can hide a cryptic differentiation, which potentially may influence the evolution of sexual dimorphism and speciation.

scholarly journals Extreme variation in recombination rate and genetic variation along the Sylvioidea neo-sex chromosome

2020 ◽  
Author(s):  
Suvi Ponnikas ◽  
Hanna Sigeman ◽  
Max Lundberg ◽  
Bengt Hansson
Keyword(s):  
Sex Chromosomes ◽  
Recombination Rate ◽  
Sex Chromosome ◽  
Bird Species ◽  
Pseudoautosomal Region ◽  
Z Chromosome ◽  
Strong Impact ◽  
Sequence Evolution ◽  
Apparent Lack ◽  
Extreme Variation

In the majority of bird species, recombination between the sex chromosome pairs in heterogametic females (ZW) is restricted to a small pseudoautosomal region (PAR), whereas recombination is ongoing along the entire Z chromosome in the homogametic males (ZZ). Recombination has a strong impact on the sequence evolution by affecting the extent of linkage, level of genetic diversity and efficacy of selection. Species within the Sylvioidea superfamily are unique among birds in having extended Z and W chromosomes (neo-sex chromosomes) formed by a fusion between the ancestral sex chromosomes and a part of chromosome 4A. So far the recombination landscape of the Sylvioidea neo-sex chromosomes remains unknown, despite its importance for understanding sequence evolution. Here, we use linkage mapping in a multi-generation pedigree to assemble, and assess the recombination rate along the entire Z chromosome of one Sylvioidea species, the great reed warbler (Acrocephalus arundinaceus). This resulted in an 87.54 Mbp and 90.19 cM large Z including the ancestral-Z, where the small PAR (0.89 Mbp) is located, and the added-Z. A striking result was an extreme variation in recombination rate along the Z in male great reed warblers with high rates at both telomeric ends, but an apparent lack of recombination over a substantial central section, covering 77% of the chromosome. This region showed a drastic loss of nucleotide diversity and accumulation of repeats compared to the highly recombining regions. Nonetheless, the evolutionary rate of genes (measured by dN/dS) did not differ between these regions, suggesting that the efficacy of selection on protein-coding sequences is not reduced by lack of recombination.

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