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Journal of Evolutionary Biology Dec 2022Understanding the evolution and regulation of nucleolar organizing regions (NORs) is important to elucidate genome structure and function. This is because ribosomal gene...
Evolution and dosage compensation of nucleolar organizing regions (NORs) mediated by mobile elements in turtles with female (ZZ/ZW) but not with male (XX/XY) heterogamety.
Understanding the evolution and regulation of nucleolar organizing regions (NORs) is important to elucidate genome structure and function. This is because ribosomal gene (rDNA) copy number and activity mediate protein biosynthesis, stress response, ageing, disease, dosage compensation and genome stability. Here, we found contrasting dosage compensation of sex-linked NORs in turtles with male and female heterogamety. Most taxa examined exhibit homomorphic rRNA gene clusters in a single autosome pair (determined by 28S rDNA fluorescence in situ hybridization), whereas NORs are sex-linked in Apalone spinifera, Pelodiscus sinensis and Staurotypus triporcatus. Full-dosage compensation upregulates the male X-NOR (determined via silver staining-AgNOR) in Staurotypus (who lacks Y-NOR) compared with female X-AgNORs. In softshell Apalone and Pelodiscus, who share homologous ZZ/ZW micro-chromosomes, their enlarged W-NOR is partially active (due to 28S rDNA invasion by R2 retroelements), whereas their smaller Z-NOR is silent in females but active in both male-Zs (presumably because the W-NOR meets cellular demands and excessive NOR activity is costly). We hypothesize that R2 disruption favoured W enlargement to add intact 28S-units, perhaps facilitated by reduced recombination during sex chromosome evolution. The molecular basis of the potentially adaptive female Z-silencing is likely intricate and perhaps epigenetic, as non-ribosomal Z genes are active in Apalone females. Yet, Emydura maquarii exhibit identical heteromorphism in their autosomal NOR (R2 invaded 28S-units and the small-autosome NOR is silent), suggesting that the softshell turtle pattern can evolve independent of sex chromosome evolution. Our study illuminates the complex sex chromosome evolution and dosage compensation of non-model systems that challenges classic paradigms.
Topics: Animals; Male; Female; Turtles; In Situ Hybridization, Fluorescence; Evolution, Molecular; Sex Chromosomes; DNA, Ribosomal; Dosage Compensation, Genetic
PubMed: 35877473
DOI: 10.1111/jeb.14064 -
Cureus Apr 2024Wilson's disease affects the metabolism of copper and is a rare hereditary disorder that is inherited autosomally recessively. The liver and brain are the main organs...
Wilson's disease affects the metabolism of copper and is a rare hereditary disorder that is inherited autosomally recessively. The liver and brain are the main organs affected by this disorder, which causes progressive hepatolenticular degeneration. A 15-year-old male patient arrived at the outpatient department (OPD) with mild abdominal pain on the right side, and both eyes showed Kayser-Fleischer (KF) rings. An abdominal ultrasound showed that the spleen was enlarged. Copper levels in urine were found to be higher. After a liver biopsy, cirrhosis, and mild chronic active hepatitis were found. The majority of hematological indicators were normal; however, a peripheral blood smear revealed mild thrombocytopenia. Wilson's disease is uncommon, so diagnosing it requires a high degree of suspicion. In circumstances of inexplicable liver cirrhosis or isolated neurological symptoms, it could go unnoticed. The only primary complaint in the case being presented was abdominal pain. However, the age upon presentation, the existence of KF rings in both eyes, and other tests helped us get the diagnosis.
PubMed: 38756326
DOI: 10.7759/cureus.58407 -
Molecular Cytogenetics Oct 2021Nance-Horan syndrome (NHS) is a rare X-linked dominant disorder caused by mutation in the NHS gene on chromosome Xp22.13. (OMIM 302350). Classic NHS manifested in males...
Nance-Horan syndrome (NHS) is a rare X-linked dominant disorder caused by mutation in the NHS gene on chromosome Xp22.13. (OMIM 302350). Classic NHS manifested in males is characterized by congenital cataracts, dental anomalies, dysmorphic facial features and occasionally intellectual disability. Females typically have a milder presentation. The majority of reported cases of NHS are the result of nonsense mutations and small deletions. Isolated X-linked congenital cataract is caused by non-recurrent rearrangement-associated aberrant NHS transcription. Classic NHS in females associated with gene disruption by balanced X-autosome translocation has been infrequently reported. We present a familial NHS associated with translocation t(X;19) (Xp22.13;q13.1). The proband, a 28-year-old female, presented with intellectual disability, dysmorphic features, short stature, primary amenorrhea, cleft palate, and horseshoe kidney, but no NHS phenotype. A karyotype and chromosome microarray analysis (CMA) revealed partial monosomy Xp/partial trisomy 19q with the breakpoint at Xp22.13 disrupting the NHS gene. Family history revealed congenital cataracts and glaucoma in the patient's mother, and congenital cataracts in maternal half-sister and maternal grandmother. The same balanced translocation t(X;19) was subsequently identified in both the mother and maternal half-sister, and further clinical evaluation of the maternal half-sister made a diagnosis of NHS. This study describes the clinical implication of NHS gene disruption due to balanced X-autosome translocations as a unique mechanism causing Nance-Horan syndrome, refines dose effects of NHS on disease presentation and phenotype expressivity, and justifies consideration of karyotype and fluorescence in situ hybridization (FISH) analysis for female patients with familial NHS if single-gene analysis of NHS is negative.
PubMed: 34620209
DOI: 10.1186/s13039-021-00566-x -
Biology of Sex Differences Jan 2019Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women. DNA methylation has been shown to play important roles in a number of cancers. There...
BACKGROUND
Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women. DNA methylation has been shown to play important roles in a number of cancers. There are differences in the DNA methylation pattern between men and women. In this study, we investigated whether this contributes to the sex-related difference of B cell CLL risk.
METHODS
Using the HumanMethylation450 BeadChip, we profiled the genome-wide DNA methylation pattern of CD19 B cells from 48 CLL patients (29 female patients and 19 male patients) and 28 healthy people (19 women and 9 men).
RESULTS
We identified 1043 sex-related differentially methylated positions (DMPs) related to CLL, 56 of which are located on autosomes and 987 on the X chromosome. Using published B cell RNA-sequencing data, we found 18 genes covered by the DMPs also have different expression levels in male and female CLL patients. Among them, TRIB1, an autosome gene, has been shown to promote tumor growth by suppressing apoptosis.
CONCLUSIONS
Our study represents the first epigenome-wide association study (EWAS) that investigates the sex-related differences in cancer, and indicated that DNA methylation differences might contribute to the sex-related difference in CLL risk.
Topics: Adult; Aged; DNA Methylation; Epigenesis, Genetic; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Sex Characteristics
PubMed: 30616686
DOI: 10.1186/s13293-018-0213-7 -
BioRxiv : the Preprint Server For... Jun 2023Sex allocation theory generally assumes maternal control of offspring sex and makes few predictions for populations evolving under paternal control. Using population...
Sex allocation theory generally assumes maternal control of offspring sex and makes few predictions for populations evolving under paternal control. Using population genetic simulations, we show that maternal and paternal control of the sex ratio lead to different equilibrium sex ratios in structured populations. Sex ratios evolved under paternal control are more female biased. This effect is dependent on the population subdivision; fewer founding individuals leads to both more biased sex ratios and a greater difference between the paternal and maternal equilibria. In addition, sexual antagonism evolves in simulations with both maternally- and paternally-acting loci. Maternally-acting loci continuously accumulate ever more female-biasing effects as male-biasing effects accumulate at paternally-acting loci. The difference in evolved sex-ratio equilibria and the evolution of sexual antagonism can be largely explained by differences in the between-group variance of maternal and paternal effects in the founding generation. These theoretical results apply to any system with biparental autosomal influence over offspring sex, opening up an exciting new line of questioning.
PubMed: 37398423
DOI: 10.1101/2023.06.14.544982 -
Philosophical Transactions of the Royal... Oct 2018Spatially varying selection with gene flow can favour the evolution of inversions that bind locally adapted alleles together, facilitate local adaptation and ultimately...
Spatially varying selection with gene flow can favour the evolution of inversions that bind locally adapted alleles together, facilitate local adaptation and ultimately drive genomic divergence between species. Several studies have shown that the rates of spread and establishment of new inversions capturing locally adaptive alleles depend on a suite of evolutionary factors, including the strength of selection for local adaptation, rates of gene flow and recombination, and the deleterious mutation load carried by inversions. Because the balance of these factors is expected to differ between X (or Z) chromosomes and autosomes, opportunities for inversion evolution are likely to systematically differ between these genomic regions, though such scenarios have not been formally modelled. Here, we consider the evolutionary dynamics of X-linked and autosomal inversions in populations evolving at a balance between migration and local selection. We identify three factors that lead to asymmetric rates of X-linked and autosome inversion establishment: (1) sex-biased migration, (2) dominance of locally adapted alleles and (3) chromosome-specific deleterious mutation loads. This theory predicts an elevated rate of fixation, and depressed opportunities for polymorphism, for X-linked inversions. Our survey of data on the genomic distribution of polymorphic and fixed inversions supports both theoretical predictions.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.
Topics: Acclimatization; Adaptation, Physiological; Alleles; Animal Migration; Animals; Chromosome Inversion; Chromosomes; Evolution, Molecular; Female; Gene Flow; Genes, Dominant; Genes, X-Linked; Genetic Drift; Genetic Fitness; Genetic Linkage; Genomics; Male; Models, Genetic; Mutation; Polymorphism, Genetic; Selection, Genetic; Sex Chromosomes
PubMed: 30150221
DOI: 10.1098/rstb.2017.0423 -
Genetics Jul 2019Hybrid male progeny from interspecies crosses are more prone to sterility or inviability than hybrid female progeny, and the male sterility and inviability often...
Hybrid male progeny from interspecies crosses are more prone to sterility or inviability than hybrid female progeny, and the male sterility and inviability often demonstrate parent-of-origin asymmetry. However, the underlying genetic mechanism of asymmetric sterility or inviability remains elusive. We previously established a genome-wide hybrid incompatibility (HI) landscape between and by phenotyping a large collection of strains each carrying a introgression. In this study, we systematically dissect the genetic mechanism of asymmetric sterility and inviability in both hybrid male and female progeny between the two species. Specifically, we performed reciprocal crosses between and different strains that each carry a GFP-labeled genomic fragment referred to as introgression, and scored the HI phenotypes in the F1 progeny. The aggregated introgressions cover 94.6% of the genome, including 100% of the chromosome. Surprisingly, we observed that two fragments that produce male sterility as an introgression rescued hybrid F1 sterility in males fathered by Subsequent backcrossing analyses indicated that a specific interaction between the -linked interaction and one autosome introgression is required to rescue the hybrid male sterility. In addition, we identified another two genomic intervals on chromosomes II and IV that can rescue the inviability, but not the sterility, of hybrid F1 males fathered by , suggesting the involvement of differential epistatic interactions in the asymmetric hybrid male fertility and inviability. Importantly, backcrossing of the rescued sterile males with led to the isolation of a 1.1-Mb genomic interval that specifically interacts with an -linked introgression, which is essential for hybrid male fertility. We further identified three genomic intervals on chromosome I, II, and III that produced inviability in all F1 progeny, dependent on or independent of the parent-of-origin. Taken together, we identified multiple independent interacting loci that are responsible for asymmetric hybrid male and female sterility, and inviability, which lays a foundation for their molecular characterization.
Topics: Animals; Caenorhabditis; Epistasis, Genetic; Female; Hybridization, Genetic; Infertility, Male; Male; X Chromosome
PubMed: 31064822
DOI: 10.1534/genetics.119.302202 -
American Journal of Human Genetics Jul 2017Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized...
Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor (REST) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.
Topics: Adolescent; Base Sequence; Chromosome Segregation; Exons; Family; Female; Fibromatosis, Gingival; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Pedigree; Repressor Proteins
PubMed: 28686854
DOI: 10.1016/j.ajhg.2017.06.006 -
Frontiers in Genetics 2019The role of chromosome Y in chronic kidney disease (CKD) remains unknown, as chromosome Y is typically excluded from genetic analysis in CKD. The complex, sex-specific... (Review)
Review
The role of chromosome Y in chronic kidney disease (CKD) remains unknown, as chromosome Y is typically excluded from genetic analysis in CKD. The complex, sex-specific presentation of CKD could be influenced by chromosome Y genetic variation, but there is limited published research available to confirm or reject this hypothesis. Although traditionally thought to be associated with male-specific disease, evidence linking chromosome Y genetic variation to common complex disorders highlights a potential gap in CKD research. Chromosome Y variation has been associated with cardiovascular disease, a condition closely linked to CKD and one with a very similar sexual dimorphism. Relatively few sources of genetic variation in chromosome Y have been examined in CKD. The association between chromosome Y aneuploidy and CKD has never been explored comprehensively, while analyses of microdeletions, copy number variation, and single-nucleotide polymorphisms in CKD have been largely limited to the autosomes or chromosome X. In many studies, it is unclear whether the analyses excluded chromosome Y or simply did not report negative results. Lack of imputation, poor cross-study comparability, and requirement for separate or additional analyses in comparison with autosomal chromosomes means that chromosome Y is under-investigated in the context of CKD. Limitations in genotyping arrays could be overcome through use of whole-chromosome sequencing of chromosome Y that may allow analysis of many different types of genetic variation across the chromosome to determine if chromosome Y genetic variation is associated with CKD.
PubMed: 31552093
DOI: 10.3389/fgene.2019.00781 -
Fa Yi Xue Za Zhi Jun 2022To estimate the system efficiency of uncle-nephew relationship identification by increasing STR markers and adding reference samples based on the test results of...
OBJECTIVES
To estimate the system efficiency of uncle-nephew relationship identification by increasing STR markers and adding reference samples based on the test results of simulated data and real samples, so as to provide references for selecting the appropriate number of STRs and reference samples for uncle-nephew relationship identification.
METHODS
Five common models of uncle-nephew relationship identification were constructed by adding different reference samples. In each model, the likelihood ratio (LR) for 10 000 pairs of uncle-nephew relationships and 10 000 pairs of unrelated individuals were simulated by detecting 19, 39 or 55 STRs, and the system efficiency at different thresholds was simulated. The samples of the Han population in Zhejiang were collected, and 55 autosomal STRs were obtained by using SiFaSTR 23plex kit, Goldenye DNA ID 22NC kit and AGCU 21+1 PCR amplification kit. When 19, 39 and 55 STRs were detected, the LR of each model and system efficiency under different thresholds were calculated and compared with the simulation results.
RESULTS
Under the same detection system, the calculated results of simulated data and corresponding true samples were basically consistent. In the same model, there was a positive correlation between the system efficiency of uncle-nephew relationship identification and the number of STRs detected. Moreover, the system efficiency of introducing relatives was higher than identifying only two individuals. The order of preference for the introduction of relatives was the full sibling (or mother) of the uncle and the full sibling (or mother) of the nephew.
CONCLUSIONS
The system efficiency of uncle-nephew relationship identification could be improved by increasing the number of STRs and introducing known relatives, which would provide the basis for selecting the most appropriate detection system and reference individuals in actual cases.
Topics: DNA; DNA Fingerprinting; Humans; Microsatellite Repeats; Polymerase Chain Reaction; Siblings
PubMed: 36221831
DOI: 10.12116/j.issn.1004-5619.2022.520407