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Results for “Chromosomes, Human, Pair 15”

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At least 19 recordsLinked to original sources

PubMed2025

Single-cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism.

Duplication 15q (dup15q) syndrome is a leading genetic cause of autism spectrum disorder, offering a key model for studying autism-related mechanisms. Using single-cell and single-nucleus RNA sequencing of cortical organoids from dup15q patient-derived iPSCs and post-mortem brain samples, we identify increased glycolysis, disrupted layer-specific marker expression, and aberrant morphology in deep-layer neurons during fetal-stage organoid development. In adolescent-adult postmortem brains, upper-layer neurons exhibit heightened transcriptional burden related to synaptic signaling, a pattern shared with idiopathic autism. Using spatial transcriptomics, we confirm these cell-type-specific disruptions in brain tissue. By gene co-expression network analysis, we reveal disease-associated modules that are well preserved between postmortem and organoid samples, suggesting metabolic dysregulation that may lead to altered neuron projection, synaptic dysfunction, and neuron hyperexcitability in dup15q syndrome.

Humans↗

PubMed2025

Activation of the imprinted Prader-Willi syndrome locus by CRISPR-based epigenome editing.

Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi syndrome (PWS) results from loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control the expression of the PWS gene SNRPN from the paternal and maternal chromosomes. We showed that either targeted transcriptional activation or DNA demethylation can activate the silenced maternal SNRPN and downstream PWS transcripts. However, these two approaches function at unique regions, preferentially activating different transcript variants and involving distinct epigenetic reprogramming mechanisms. Remarkably, transient expression of the targeted demethylase leads to stable, long-term maternal SNRPN expression in PWS iPSCs. This work uncovers targeted epigenetic manipulations to reprogram a disease-associated imprinted locus and suggests possible therapeutic interventions.

Prader-Willi Syndrome↗

PubMed2025

Rescue of imprinted genes by epigenome editing in human cellular models of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genomic imprinting disorder caused by the loss of function of the paternal chromosome 15q11-13, resulting in a spectrum of symptoms associated with hypothalamic dysfunction. PWS patients lack the expression of paternally expressed genes (PEGs) in the 15q11-13 locus but possess an epigenetically silenced set of these genes in the maternal allele. Thus, activation of these silenced genes can serve as a therapeutic target for PWS. Here, we leverage CRISPR-based epigenome editing system to modulate the DNA methylation status of the PWS imprinting control region (PWS-ICR) in induced pluripotent stem cells (iPSCs) derived from PWS patients. Successful demethylation in the PWS-ICR restores the PEG expression from the maternal allele and reorganizes the methylation patterns in other PWS-associated imprinted regions beyond the PWS-ICR. Remarkably, these corrected epigenomic patterns and PEG expression are maintained following the differentiation of these cells into hypothalamic organoids. Finally, the single-cell transcriptomic analysis of epigenome-edited organoids demonstrates a partial restoration of the transcriptomic dysregulation observed in PWS. This study highlights the utility of epigenome editing technology as a therapeutic approach in addressing PWS and potentially other imprinting disorders.

Prader-Willi Syndrome↗

PubMed2026

Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.

Bladder cancer is the ninth most common cancer worldwide, caused by genetic and environmental risk factors. Here, we report the findings of a multi-population meta-analysis of genome-wide association studies, including 32,470 individuals with and 1,753,462 without bladder cancer. We identify 70 independent risk loci, of which 43 are novel. Using a 70-marker polygenic risk score (HR = 1.63 per standard deviation), we increase the area under the curve from 0.71 (baseline risk model) to 0.75. Integrative analyses reveal the enrichment of the associated variants within accessible chromatin regions, and of the prioritized genes within pathways for xenobiotic metabolism and smoking behavior. Specifically, we show that the 15q25.1 variant rs71581744-ACCCC/A co-localizes with tissue-specific CHRNA3 expression, modulates mRNA stability, and associates with risk of muscle-invasive bladder cancer among current smokers. Together, these findings substantially expand the known genetic architecture of bladder cancer risk and highlight the germline regulation of smoking behavior as a mechanism driving bladder cancer susceptibility.

Humans↗

PubMed1976

Detection of nucleolus organizer regions in chromosomes of human, chimpanzee, gorilla, orangutan and gibbon.

Nucleolus organizer regions were detected by the Ag-AS silver method in fixed metaphase chromosomes from human and primates. In the human, silver was deposited in the secondary constriction of a maximum of five pairs of acrocentric chromosomes: 13, 14, 15, 21 and 22. The chimpanzee also had five pairs of acrocentric chromosomes stained, corresponding to human numbers 13, 14, 18, 21 and 22. A gibbon had a single pair of chromosomes with a secondary constriction, which corresponded to the nucleolus organizer region. In each case the Ag-AS method detected the sites which have been shown by in situ hybridization to contain the ribosomal RNA genes. An orangutan had eight pairs of acrocentric chromosomes stained with Ag-AS, probably corresponding to human numbers 13, 14, 15, 18, 21 and 22, plus two others. Two gorillas had silver stain over two pairs of small acrocentric chromosomes and at the telomere of one chromosome 1. The larger gorilla acrocentric chromosomes had no silver stain although they all had secondary constrictions and entered into satellite associations.

Animals↗

PubMed1977

Stability of centromere-center distances in normal human metaphases.

Centromere-center distances were analyzed in 50 normal female and 100 normal male metaphases. Compared with the random distribution of all chromosomes, chromosome pair 6 had a significantly different distribution in both female and male metaphases. Moreover, a significant peripheral location of chromosome pairs 4 and 5 and a significant central location of chromosome pairs 13, 15, 21, and 22 were found in male metaphases. But no specific peripheral location could be assigned to the X or Y chromosomes. No inter- nor intraindividual differences or sex-dependent variation in centromere-center distances were observed. Variance analyses demonstrated consistent centromere-center distances in normal human metaphases obtained from individuals of the same age. The constancy of these chromosome distributions may correlate with chromosome duplication pattern, chromosome length, and chromosome structure.

Adult↗

PubMed1975

Relative position of trypsin banded homologous chromosomes in human (female) metaphase figures.

"Generalized distances" between centromeres were statistically analyzed (chi2 test) on 50 normal female trypsin-banded metaphase figures. This study revealed that the homologous chromosomes of the pairs 13, 17, 14, and 21 lie closer together than would be expected by a reference distribution, and this in a statistically significant way. The same relative position was demonstrated for the chromosome groups 13-14, 13-21, 14-21, 15-22, and 14-22. Evidences were collected that also showed that homologous chromosomes of the pairs 1, 19, and 20 and the chromosome groups 15-21, 13-15, and 18-20 tend to lie closer together. Giving a functional interpretation to the phenomenon of non-random distribution of chromosomes in metaphase figures, it may be suggested that the chromosomes 13, 14, and 21 are involved in the organization of the human nucleolar organizers, more frequently than the other D- and G-group chromosomes.

Cell Nucleus↗

PubMed1977

The nucleolar cycle in man.

Tissue cultures of human embryonal kidney and ovary were examined. In the nuclei of both tissues, one to ten nucleoli have been found. The maximum number of nucleoli is connected with the gene expression of rDNA of the 10 nucleolus organizers of chromosome pairs Nos. 13, 14, 15, 21 and 22, which have secondary constrictions and are the satellite chromosomes in man. The small percentage of cells with 10, 9 and 8 nucleoli is attributed to the rapid association of 3 of the homologous acrocentrics (perhaps of group D). Two of the satellite (SAT) pairs probably associate later after mitosis. The process of fusion is dynamic, resulting in one interphase nucleous--a manifestation of the association of all SAT chromosomes. Dissociation of the nucleolus occurs upon entering prophase, due to the condensation of the chromosomes and retreat of rDNA to the respective secondary constrictions. As a result, the nucleolar number increases again. The pattern of the nucleolar kinetics within the course of one mitotic division is described.

Cell Nucleolus↗

PubMed1978

Lateral asymmetry in human constitutive heterochromatin: frequency and inheritance.

The relative frequencies and types of lateral asymmetry found in chromosomes 1, 9, 15, 16, and the Y were determined. The pattern of asymmetry is simple in chromosomes 15, 16, and the Y but compound in 1 and possibly also 9. The pattern of compound lateral asymmetry is a stable heteromorphism inherited in a simple Mendelian way and is an efficient morphological discriminator between the members of the no. 1 chromosome pair.

Chromosomes, Human↗

PubMed1976

[Sequential staining for G- and C-banding of chromosomes in the analysis of the morphology of the short arms of human acrocentric chromosomes].

Sequential staining for G- and C-banding of acrocentric chromosomes of 8 persons showed that the large heterochromatin region occurred more frequently in chromosome 15 than in chromosomes 13 and 14, and in chromosome 22 more frequently than in chromosome 21. There proved to be no correlation between the size of the heterochromatic region and the short arm of the acrocentric chromosomes. The frequency of occurrence of the satellites in the 8 persons was approximately the same for all the acricentric pairs. The C-banded satellite region of the homologous chromosomes is often heteromorphic.

Chromosome Aberrations↗

PubMed1977

Quantitative analysis of C-bands based on optical density profiles in human chromosomes.

A method of quantitative analysis of C segments in human chromosomes 1, 9, and 16 based on longitudinal densitometry has been developed. The way of fitting apparatus data to visual estimates is represented. Density curve parameters not dependent on stain intensity were used. The general C band length error is approx. 0.05 micrometer. Heteromorphic chromosome 16 pairs have been investigated with this method. A significant difference (about 0.18 micrometer) between C bands of the homologues has been detected in chromosome 16. It has been calculated that C bands can be distinquished if the mean difference between the length of the homologues is more than 15%.

Chromosomes, Human↗

PubMed1977

Non-random association of trypsin-banded human acrocentric chromosomes.

This paper deals with a computer-aided study of the associations between acrocentric chromosomes as well as between those other chromosomes which in our investigations were revealed to be significantly closer to each other than random. The chromosome pairs were identified by a trypsin-banding technique. The method used has been elaborated previously with the specific aim of determining associations in a manner that avoids all subjective criteria. The tendency for association between homologous chromosomes is in decreasing order: 21 and 13 greater than 1 greater than 14, 18 and 19 greater than 17. Among the nonhomologous acrocentric chromosomes the significant tendencies for associations are between D-D: 13-14 greater than 13-15 greater than 14-15; between D-G: 13-21 greater than 14-21 greater than 13-22 greater than 15-22. The implication of the different tendencies to associate are dicussed in terms of aetiology of numerical and structural chromosome abnormalities.

Adult↗

PubMed1978

A new cytogenetic aspect of polycythemia vera.

The cytogenetic findings in a group of 15 polycythemic patients are reported. G and C banding techniques were used on bone marrow and peripheral blood preparations. Major chromosomal aberrations were found in four out of the 15 patients, an incidence similar to that found in other studies on polymorphism. The most interesting finding concerned the chromosomal polymorphism of the pair 19. A possible relation to the etiology of the disease is discussed.

Adult↗

PubMed1979

Familial urinary tract anomalies: association with the major histocompatibility complex in man.

Histocompatibility typing of a family with 15 members and a history of ureteropelvic junction stenosis and 4 families with 23 members and a history of vesicoureteral reflux revealed that these anomalies of the urinary tract may be hereditary and segregate with histocompatibility haplotype within a family. Thus, a close linkage of childhood reflux and ureteral stenosis with that of the major histocompatibility complex of man is suggested. If confirmed by further family studies it will place the gene(s) for vesicoureteral reflux and ureteral stenosis on the 6th pair of human chromosome and open the possibility of using histocompatibility typing as a marker for these anomalies within a family.

Adolescent↗

PubMed1977

Translocation D/D involving two homologous chromosomes of the pair 15.

A translocation between two homologues of chromosomes 15 was identified in a phenotypically normal female with the R-banding technique. The C-banding technique demonstrated an abnormally large band on the translocation chromosome. This finding suggests a possibility that the translocation might be due to breaks in the short arms or to fusion at telomeric ends. The patient had four spontaneous abortions and no normal pregnancy.

Abortion, Habitual↗

PubMed2001

Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.

Human chromosome 10q21-22 harbors USH1F in a region of conserved synteny to mouse chromosome 10. This region of mouse chromosome 10 contains Pcdh15, encoding a protocadherin gene that is mutated in ames waltzer and causes deafness and vestibular dysfunction. Here we report two mutations of protocadherin 15 (PCDH15) found in two families segregating Usher syndrome type 1F. A Northern blot probed with the PCDH15 cytoplasmic domain showed expression in the retina, consistent with its pathogenetic role in the retinitis pigmentosa associated with USH1F.

Aged↗

PubMed1977

Relative positions of chromosome 1 loci Fy, PGM1, Sc, UMPK, Rh, PGD and ENO1 in man.

Ongoing linkage studies of red cell antigens and enzymes in many families along with concentration on a large Mennonite kindred segregating for Sc have resulted in lods, recombinant: nonrecombinant counts and multi-point information which support an order with approximate recombination fractions as measured in the male as follows: Fy--.25--PGM1--.20--Sc--less than .05--UMPK--.15--Rh--.20--PGD, with ENO1 close to PGD. The insertion of Sc and UMPK between PGM1 and Rh allows the recognition of double crossing-over between the latter pair; indications are that this is not a rare event in the female. In the male no evidence of double crossing-over was found in the similar distances PGM1--Rh and Sc--PGD in 13 and 19 opportunities respectively.

Blood Group Antigens↗

PubMed1977

The origin and behavior of two isodicentric bisatellited chromosomes.

Karyotyping revealed three cell lines in a boy with mental retardation and few other abnormalities. Thirty cells exhibited a normal karyotype, and 54 had an extra acrocentric chromosome of E group size with satellites on the long and short arms. The remaining 20 cells each had, in addition to the first marker (M1), a second tiny bisatellited chromosome (M2). C-banding demonstrated that both markers were dicentric. G-, C-, and Q-banding and satellite association data were consistent with the markers having originated from chromosome 15 material. We propose that M1 was formed from a meiotic breakage and a chromatid fusion in the proximal long arms of an acrocentric pair. This would have produced a symmetrical isodicentric chromosomes, plus one or two acentric fragments. M2 then could have resulted from a dicentric bridge-break-synthesis-reunion phenomenon. This model of abnormal meiotic exchange can be generalized to encompass the formation of other dicentric isochromosome cases of isochromosome X.

Azure Stains↗