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Chromosome Research : An International... Sep 2016The recurrent occurrence of sex-autosome translocations during mammalian evolution suggests common mechanisms enabling a precise control of meiotic synapsis,...
The recurrent occurrence of sex-autosome translocations during mammalian evolution suggests common mechanisms enabling a precise control of meiotic synapsis, recombination and inactivation of sex chromosomes. We used immunofluorescence and FISH to study the meiotic behaviour of sex chromosomes in six species of Bovidae with evolutionary sex-autosome translocations (Tragelaphus strepsiceros, Taurotragus oryx, Tragelaphus imberbis, Tragelaphus spekii, Gazella leptoceros and Nanger dama ruficollis). The autosomal regions of fused sex chromosomes showed normal synapsis with their homologous counterparts. Synapsis in the pseudoautosomal region (PAR) leads to the formation of characteristic bivalent (in T. imberbis and T. spekii with X;BTA13/Y;BTA13), trivalent (in T. strepsiceros and T. oryx with X/Y;BTA13 and G. leptoceros with X;BTA5/Y) and quadrivalent (in N. dama ruficollis with X;BTA5/Y;BTA16) structures at pachynema. However, when compared with other mammals, the number of pachynema lacking MLH1 foci in the PAR was relatively high, especially in T. imberbis and T. spekii, species with both sex chromosomes involved in sex autosome translocations. Meiotic transcriptional inactivation of the sex-autosome translocations assessed by γH2AX staining was restricted to their gonosomal regions. Despite intraspecies differences, the evolutionary fixation of sex-autosome translocations among bovids appears to involve general mechanisms ensuring sex chromosome pairing, synapsis, recombination and inactivation.
Topics: Animals; Chromosome Painting; Chromosome Pairing; Chromosome Segregation; Fluorescent Antibody Technique; In Situ Hybridization, Fluorescence; Meiosis; Ruminants; Sex Chromosomes; Translocation, Genetic
PubMed: 27136937
DOI: 10.1007/s10577-016-9524-x -
Molecular Ecology Resources Nov 2023Single-nucleotide polymorphism (SNP) analysis is a powerful tool for population genetics, pedigree reconstruction and phenotypic trait mapping. However, the untapped...
Single-nucleotide polymorphism (SNP) analysis is a powerful tool for population genetics, pedigree reconstruction and phenotypic trait mapping. However, the untapped potential of SNP markers to discriminate the sex of individuals in species with reduced sexual dimorphism or of individuals during immature stages remains a largely unexplored avenue. Here, we developed a novel protocol for molecular sexing of birds based on the detection of unique Z- and W-linked SNP markers. Our method is based on the identification of two unique loci, one in each sexual chromosome. Individuals are considered males when they show no calls for the W-linked SNP and are heterozygous or homozygous for the Z-linked SNP, while females exhibit both Z- and W-linked SNP calls. We validated the method in the Jackdaw (Corvus monedula). The reduced sexual dimorphism in this species makes it difficult to identify the sex of individuals in the wild. We assessed the reliability of the method using 36 individuals of known sex and found that their sex was correctly assigned in 100% of cases. The sex-linked markers also proved to be widely applicable for discriminating males and females from a sample of 927 genotyped individuals at different maturity stages, with an accuracy of 99.5%. Since SNP markers are increasingly used in quantitative genetic analyses of wild populations, the approach we propose has great potential to be integrated into broader genetic research programmes without the need for additional sexing techniques.
Topics: Humans; Male; Female; Animals; Reproducibility of Results; Genotype; Birds; Heterozygote; Sex Characteristics; Polymorphism, Single Nucleotide
PubMed: 37675830
DOI: 10.1111/1755-0998.13862 -
Endocrine Connections May 2023The transcriptional landscape of Klinefelter syndromeduring early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in...
OBJECTIVE
The transcriptional landscape of Klinefelter syndromeduring early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males induced pluripotent stem cells (iPSCs) obtained from patients with different genomic backgrounds and ethnicities.
DESIGN AND METHOD
We derived and characterized 15 iPSC lines from four Saudi 47,XXY KS patients and one Saudi 46,XY male. We performed a comparative transcriptional analysis using the Saudi KS-iPSCs and a cohort of European and North American KS-iPSCs.
RESULTS
We identified a panel of X-linked and autosomal genes commonly dysregulated in Saudi and European/North American KS-iPSCs vs 46,XY controls. Our findings demonstrate that seven PAR1 and nine non-PAR escape genes are consistently dysregulated and mostly display comparable transcriptional levels in both groups. Finally, we focused on genes commonly dysregulated in both iPSC cohorts and identified several gene-ontology categories highly relevant to KS physiopathology, including aberrant cardiac muscle contractility, skeletal muscle defects, abnormal synaptic transmission, and behavioral alterations.
CONCLUSIONS
Our results indicate that a transcriptomic signature of X chromosome overdosage in KS is potentially attributable to a subset of X-linked genes sensitive to sex chromosome dosage and escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic makeup.
PubMed: 36971776
DOI: 10.1530/EC-22-0515 -
Scientific Reports Jul 2023The genetic architecture of the QT interval, defined as the period from onset of depolarisation to completion of repolarisation of the ventricular myocardium, is...
The genetic architecture of the QT interval, defined as the period from onset of depolarisation to completion of repolarisation of the ventricular myocardium, is incompletely understood. Only a minor part of the QT interval variation in the general population has been linked to autosomal variant loci. Altered X chromosome dosage in humans, as seen in sex chromosome aneuploidies such as Turner syndrome (TS) and Klinefelter syndrome (KS), is associated with altered QTc interval (heart rate corrected QT), indicating that genes, located in the pseudoautosomal region 1 of the X and Y chromosomes may contribute to QT interval variation. We investigate the dosage effect of the pseudoautosomal gene SLC25A6, encoding the membrane ADP/ATP translocase 3 in the inner mitochondrial membrane, on QTc interval duration. To this end we used human participants and in vivo zebrafish models. Analyses in humans, based on 44 patients with KS, 44 patients with TS, 59 male and 22 females, revealed a significant negative correlation between SLC25A6 expression level and QTc interval duration. Similarly, downregulation of slc25a6 in zebrafish increased QTc interval duration with pharmacological inhibition of K channels restoring the systolic duration, whereas overexpression of SLC25A6 shortened QTc, which was normalized by pharmacological activation of K channels. Our study demonstrate an inverse relationship between SLC25A6 dosage and QTc interval indicating that SLC25A6 contributes to QT interval variation.
Topics: Animals; Female; Humans; Male; Adenosine Triphosphate; Electrocardiography; Klinefelter Syndrome; Long QT Syndrome; Turner Syndrome; X Chromosome; Zebrafish; Adenine Nucleotide Translocator 3
PubMed: 37495650
DOI: 10.1038/s41598-023-38867-3 -
Journal of Oral and Maxillofacial... Apr 2019One of the most common causes of short stature is a defect of the short stature homeobox-containing (SHOX) gene, which is located in pseudoautosomal region 1 on the...
One of the most common causes of short stature is a defect of the short stature homeobox-containing (SHOX) gene, which is located in pseudoautosomal region 1 on the distal end of the short arm of chromosomes Xp22.33 and Yp11.32. More than 300 different mutations in the SHOX gene responsible for short stature syndrome have been described. The phenotypic expression of SHOX haploinsufficiency is remarkably varied. The 3 typical clinical presentations, from least to most severe, are idiopathic short stature without skeletal malformations, Leri-Weill dyschondrosteosis (LWD), and Langer mesomelic dysplasia, which is believed to represent the homozygous form of LWD. Despite a higher prevalence in women, suggesting the potentiating action of high estrogen levels on the effects of SHOX deficiency, the syndrome was initially believed to have an autosomal pattern of inheritance. In reality, heterozygous SHOX mutations can be transferred from the Y to the X chromosome and vice versa. This phenomenon is called "the jumping SHOX gene" and corresponds to a pseudoautosomal dominant inheritance. LWD is characterized by mesomelic short stature and Madelung deformity defined by an upward and medial displacement of the radial joint surface, which restricts range of motion. Less specific dysmorphic signs associated with LWD, such as short hands and feet, scoliosis, or muscular hypertrophy, have been described. When reviewing the dental and maxillofacial signs, only limited and summary data (micrognathia and high arched palate) have been published in the literature. This report presents a case of LWD that highlights many other noteworthy dental and maxillofacial signs that are important to clearly identify and appropriately treat.
Topics: Growth Disorders; Humans; Male; Maxillofacial Abnormalities; Osteochondrodysplasias; Short Stature Homeobox Protein; Young Adult
PubMed: 30529377
DOI: 10.1016/j.joms.2018.11.001 -
Molecular Ecology Mar 2023Whole-genome surveys of genetic diversity and geographic variation often yield unexpected discoveries of novel structural variation, which long-read DNA sequencing can...
Whole-genome surveys of genetic diversity and geographic variation often yield unexpected discoveries of novel structural variation, which long-read DNA sequencing can help clarify. Here, we report on whole-genome phylogeography of a bird exhibiting classic vicariant geographies across Australia and New Guinea, the blue-faced honeyeater (Entomyzon cyanotis), and the discovery and characterization of a novel neo-Z chromosome by long-read sequencing. Using short-read genome-wide SNPs, we inferred population divergence events within E. cyanotis across the Carpentarian and other biogeographic barriers during the Pleistocene (~0.3-1.7 Ma). Evidence for introgression between nonsister populations supports a hypothesis of reticulate evolution around a triad of dynamic barriers around Pleistocene Lake Carpentaria between Australia and New Guinea. During this phylogeographic survey, we discovered a large (134 Mbp) neo-Z chromosome and we explored its diversity, divergence and introgression landscape. We show that, as in some sylvioid passerine birds, a fusion occurred between chromosome 5 and the Z chromosome to form a neo-Z chromosome; and in E. cyanotis, the ancestral pseudoautosomal region (PAR) appears nonrecombinant between Z and W, along with most of the fused chromosome 5. The added recombination-suppressed portion of the neo-Z (~37.2 Mbp) displays reduced diversity and faster population genetic differentiation compared with the ancestral-Z. Yet, the new PAR (~17.4 Mbp) shows elevated diversity and reduced differentiation compared to autosomes, potentially resulting from introgression. In our case, long-read sequencing helped clarify the genomic landscape of population divergence on autosomes and sex chromosomes in a species where prior knowledge of genome structure was still incomplete.
Topics: Animals; Phylogeography; Sex Chromosomes; Genomics; Arecaceae; Passeriformes
PubMed: 35797346
DOI: 10.1111/mec.16604 -
Journal of Dairy Science Sep 2016Imputation is a cost-effective approach to augment marker data for genomic selection and genome-wide association studies. However, most imputation studies have focused...
Imputation is a cost-effective approach to augment marker data for genomic selection and genome-wide association studies. However, most imputation studies have focused on autosomes. Here, we assessed the imputation of markers on the X chromosome in Holstein cattle for nongenotyped animals and animals genotyped with low-density (Illumina BovineLD, Illumina Inc., San Diego, CA) chips, using animals genotyped with medium-density (Illumina BovineSNP50) chips. A total of 26,884 genotyped Holstein individuals genotyped with medium-density chips were used in this study. Imputation was carried out using FImpute V2.2. The following parameters were examined: treating the pseudoautosomal region as autosomal or as X specific, different sizes of reference groups, different male/female proportions in the reference group, and cumulated degree of relationship between the reference group and target group. The imputation accuracy of markers on the X chromosome was improved if the pseudoautosomal region was treated as autosomal. Increasing the proportion of females in the reference group improved the imputation accuracy for the X chromosome. Imputation for nongenotyped animals in general had lower accuracy compared with animals genotyped with the low-density single nucleotide polymorphism array. In addition, higher cumulative pedigree relationships between the reference group and the target animal led to higher imputation accuracy. In the future, better marker coverage of the X chromosome should be developed to facilitate genomic studies involving the X chromosome.
Topics: Animals; Breeding; Cattle; Female; Genetic Markers; Genome; Genome-Wide Association Study; Genomics; Genotype; Male; Pedigree; Polymorphism, Single Nucleotide; X Chromosome
PubMed: 27423959
DOI: 10.3168/jds.2016-11160 -
BMC Genomics Apr 2015In mammalian meiotic prophase, homologous chromosome recognition is aided by formation and repair of programmed DNA double-strand breaks (DSBs). Subsequently, stable...
BACKGROUND
In mammalian meiotic prophase, homologous chromosome recognition is aided by formation and repair of programmed DNA double-strand breaks (DSBs). Subsequently, stable associations form through homologous chromosome synapsis. In male mouse meiosis, the largely heterologous X and Y chromosomes synapse only in their short pseudoautosomal regions (PARs), and DSBs persist along the unsynapsed non-homologous arms of these sex chromosomes. Asynapsis of these arms and the persistent DSBs then trigger transcriptional silencing through meiotic sex chromosome inactivation (MSCI), resulting in formation of the XY body. This inactive state is partially maintained in post-meiotic haploid spermatids (postmeiotic sex chromatin repression, PSCR). For the human, establishment of MSCI and PSCR have also been reported, but X-linked gene silencing appears to be more variable compared to mouse. To gain more insight into the regulation and significance of MSCI and PSCR among different eutherian species, we have performed a global analysis of XY pairing dynamics, DSB repair, MSCI and PSCR in the domestic dog (Canis lupus familiaris), for which the complete genome sequence has recently become available, allowing a thorough comparative analyses.
RESULTS
In addition to PAR synapsis between X and Y, we observed extensive self-synapsis of part of the dog X chromosome, and rapid loss of known markers of DSB repair from that part of the X. Sequencing of RNA from purified spermatocytes and spermatids revealed establishment of MSCI. However, the self-synapsing region of the X displayed higher X-linked gene expression compared to the unsynapsed area in spermatocytes, and was post-meiotically reactivated in spermatids. In contrast, genes in the PAR, which are expected to escape MSCI, were expressed at very low levels in both spermatocytes and spermatids. Our comparative analysis was then used to identify two X-linked genes that may escape MSCI in spermatocytes, and 21 that are specifically re-activated in spermatids of human, mouse and dog.
CONCLUSIONS
Our data indicate that MSCI is incomplete in the dog. This may be partially explained by extensive, but transient, self-synapsis of the X chromosome, in association with rapid completion of meiotic DSB repair. In addition, our comparative analysis identifies novel candidate male fertility genes.
Topics: Animals; Animals, Domestic; Chromosomes, Mammalian; DNA Breaks, Double-Stranded; DNA Repair; Dogs; Humans; Male; Meiosis; Mice; Sex Chromosomes; Spermatocytes; Spermatogenesis; Testis; X Chromosome Inactivation
PubMed: 25884295
DOI: 10.1186/s12864-015-1501-9 -
PLoS Genetics Nov 2014The human sex chromosomes differ in sequence, except for the pseudoautosomal regions (PAR) at the terminus of the short and the long arms, denoted as PAR1 and PAR2. The...
The human sex chromosomes differ in sequence, except for the pseudoautosomal regions (PAR) at the terminus of the short and the long arms, denoted as PAR1 and PAR2. The boundary between PAR1 and the unique X and Y sequences was established during the divergence of the great apes. During a copy number variation screen, we noted a paternally inherited chromosome X duplication in 15 independent families. Subsequent genomic analysis demonstrated that an insertional translocation of X chromosomal sequence into the Y chromosome generates an extended PAR [corrected].The insertion is generated by non-allelic homologous recombination between a 548 bp LTR6B repeat within the Y chromosome PAR1 and a second LTR6B repeat located 105 kb from the PAR boundary on the X chromosome. The identification of the reciprocal deletion on the X chromosome in one family and the occurrence of the variant in different chromosome Y haplogroups demonstrate this is a recurrent genomic rearrangement in the human population. This finding represents a novel mechanism shaping sex chromosomal evolution.
Topics: Animals; Chromosomes; Chromosomes, Human, X; Chromosomes, Human, Y; Evolution, Molecular; Haplotypes; Hominidae; Homologous Recombination; Humans; Polymorphism, Genetic; Repetitive Sequences, Nucleic Acid; Translocation, Genetic
PubMed: 25375121
DOI: 10.1371/journal.pgen.1004578 -
Molecular Cytogenetics Jul 2021Constitutional telomeric associations are very rare events and the mechanism underlying their development is not well understood.
BACKGROUND
Constitutional telomeric associations are very rare events and the mechanism underlying their development is not well understood.
CASE PRESENTATION
We here describe a female case of Turner syndrome with a 45,X,add(22)(p11.2)[25]/45,X[5]. We reconfirmed this karyotype by FISH analysis as 45,X,dic(Y;22)(p11.3;p11.2)[28]/45,X[2].ish dic(Y;22)(SRY+,DYZ1+). A possible mechanism underlying this mosaicism was a loss of dic(Y;22) followed by a monosomy rescue of chromosome 22. However, SNP microarray analysis revealed no loss of heterozygosity (LOH) in chromosome 22, although a mosaic pattern of LOH was clearly detectable at the pseudoautosomal regions of the sex chromosomes.
CONCLUSIONS
Our results suggest that the separation of the dicentric chromosome at the junction resulted in a loss of chromosome Y without a loss of chromosome 22, leading to this patient's unique mosaicism. Although telomere signals were not detected by FISH at the junction, it is likely that the original dic(Y;22) chromosome was generated by unstable telomeric associations. We propose a novel "pulled apart" mechanism as the process underlying this mosaicism.
PubMed: 34238329
DOI: 10.1186/s13039-021-00556-z