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Journal of Otology Sep 2018Waardenburg syndrome is a rare disease characterized by sensorineural deafness in association with pigmentary defects. Depending on additional symptoms, WS have been... (Review)
Review
Waardenburg syndrome is a rare disease characterized by sensorineural deafness in association with pigmentary defects. Depending on additional symptoms, WS have been classified into four types. Waardenburg syndrome type 4, also called as Waardenburg Shah Syndrome is a very rare congenital disorder with astounding variable clinical expression, characterized by pigmentary abnormalities of the hair (A white forelock of hair, premature graying) and pigmentary changes of the iris such as heterochromia or homochromia irides, sensorineural deafness and Hirschsprung disease. Three genes have been bestowed so far in consociation with EDNRB, EDN3, and SOX10 genes. The pattern of inheritance is multifarious with the SOX10 mutation affiliation with autosomal dominant inheritance whereas the EDNRB and EDN3 genes are passed down in an autosomally recessive pattern.
PubMed: 30559775
DOI: 10.1016/j.joto.2018.05.005 -
PLoS Genetics Oct 2022Meiosis in males of higher dipterans is achiasmate. In their spermatocytes, pairing of homologs into bivalent chromosomes does not include synaptonemal complex and...
Meiosis in males of higher dipterans is achiasmate. In their spermatocytes, pairing of homologs into bivalent chromosomes does not include synaptonemal complex and crossover formation. While crossovers preserve homolog conjunction until anaphase I during canonical meiosis, an alternative system is used in dipteran males. Mutant screening in Drosophila melanogaster has identified teflon (tef) as being required specifically for alternative homolog conjunction (AHC) of autosomal bivalents. The additional known AHC genes, snm, uno and mnm, are needed for the conjunction of autosomal homologs and of sex chromosomes. Here, we have analyzed the pattern of TEF protein expression. TEF is present in early spermatocytes but cannot be detected on bivalents at the onset of the first meiotic division, in contrast to SNM, UNO and MNM (SUM). TEF binds to polytene chromosomes in larval salivary glands, recruits MNM by direct interaction and thereby, indirectly, also SNM and UNO. However, chromosomal SUM association is not entirely dependent on TEF, and residual autosome conjunction occurs in tef null mutant spermatocytes. The higher tef requirement for autosomal conjunction is likely linked to the quantitative difference in the amount of SUM protein that provides conjunction of autosomes and sex chromosomes, respectively. During normal meiosis, SUM proteins are far more abundant on sex chromosomes compared to autosomes. Beyond promoting SUM recruitment, TEF has a stabilizing effect on SUM proteins. Increased SUM causes excess conjunction and consequential chromosome missegregation during meiosis I after co-overexpression. Similarly, expression of SUM without TEF, and even more potently with TEF, interferes with chromosome segregation during anaphase of mitotic divisions in somatic cells, suggesting that the known AHC proteins are sufficient for establishment of ectopic chromosome conjunction. Overall, our findings suggest that TEF promotes alternative homolog conjunction during male meiosis without being part of the final physical linkage between chromosomes.
Topics: Animals; Male; Drosophila melanogaster; Drosophila; Drosophila Proteins; Polytetrafluoroethylene; Chromosome Segregation; Meiosis; Sex Chromosomes; Chromosome Pairing
PubMed: 36251690
DOI: 10.1371/journal.pgen.1010469 -
Current Opinion in Genetics &... Apr 2015In Caenorhabditis elegans, males have one X chromosome and hermaphrodites have two. Emerging evidence indicates that the male X is transcriptionally more active than... (Review)
Review
In Caenorhabditis elegans, males have one X chromosome and hermaphrodites have two. Emerging evidence indicates that the male X is transcriptionally more active than autosomes to balance the single X to two sets of autosomes. Because upregulation is not limited to males, hermaphrodites need to strike back and downregulate expression from the two X chromosomes to balance gene expression in their genome. Hermaphrodite-specific downregulation involves binding of the dosage compensation complex to both Xs. Advances in recent years revealed that the action of the dosage compensation complex results in compaction of the X chromosomes, changes in the distribution of histone modifications, and ultimately limiting RNA Polymerase II loading to achieve chromosome-wide gene repression.
Topics: Animals; Caenorhabditis elegans; DNA, Helminth; Dosage Compensation, Genetic; Down-Regulation; Up-Regulation; X Chromosome
PubMed: 25966908
DOI: 10.1016/j.gde.2015.04.001 -
Biology Letters Nov 2020Chromosome fusion and fission are primary mechanisms of karyotype evolution. In particular, the fusion of a sex chromosome and an autosome has been proposed as a...
Chromosome fusion and fission are primary mechanisms of karyotype evolution. In particular, the fusion of a sex chromosome and an autosome has been proposed as a mechanism to resolve intralocus sexual antagonism. If sexual antagonism is common throughout the genome, we should expect to see an excess of fusions that join sex chromosomes and autosomes. Here, we present a null model that provides the probability of a sex chromosome autosome fusion, assuming all chromosomes have an equal probability of being involved in a fusion. This closed-form expression is applicable to both male and female heterogametic sex chromosome systems and can accommodate unequal proportions of fusions originating in males and females. We find that over 25% of all chromosomal fusions are expected to join a sex chromosome and an autosome whenever the diploid autosome count is fewer than 16, regardless of the sex chromosome system. We also demonstrate the utility of our model by analysing two contrasting empirical datasets: one from and one from the jumping spider genus . We find that in the case of , there is a significant excess of sex chromosome autosome fusions but that in there are far fewer sex chromosome autosome fusions than would be expected under our null model.
Topics: Animals; Female; Genome; Karyotyping; Male; Probability; Sex Chromosomes; X Chromosome
PubMed: 33232649
DOI: 10.1098/rsbl.2020.0648 -
American Journal of Human Genetics Jun 202310 years ago, a detailed analysis showed that only 33% of genome-wide association study (GWAS) results included the X chromosome. Multiple recommendations were made to... (Review)
Review
10 years ago, a detailed analysis showed that only 33% of genome-wide association study (GWAS) results included the X chromosome. Multiple recommendations were made to combat such exclusion. Here, we re-surveyed the research landscape to determine whether these earlier recommendations had been translated. Unfortunately, among the genome-wide summary statistics reported in 2021 in the NHGRI-EBI GWAS Catalog, only 25% provided results for the X chromosome and 3% for the Y chromosome, suggesting that the exclusion phenomenon not only persists but has also expanded into an exclusionary problem. Normalizing by physical length of the chromosome, the average number of studies published through November 2022 with genome-wide-significant findings on the X chromosome is ∼1 study/Mb. By contrast, it ranges from ∼6 to ∼16 studies/Mb for chromosomes 4 and 19, respectively. Compared with the autosomal growth rate of ∼0.086 studies/Mb/year over the last decade, studies of the X chromosome grew at less than one-seventh that rate, only ∼0.012 studies/Mb/year. Among the studies that reported significant associations on the X chromosome, we noted extreme heterogeneities in data analysis and reporting of results, suggesting the need for clear guidelines. Unsurprisingly, among the 430 scores sampled from the PolyGenic Score Catalog, 0% contained weights for sex chromosomal SNPs. To overcome the dearth of sex chromosome analyses, we provide five sets of recommendations and future directions. Finally, until the sex chromosomes are included in a whole-genome study, instead of GWASs, we propose such studies would more properly be referred to as "AWASs," meaning "autosome-wide scans."
Topics: Humans; Genome-Wide Association Study; Sex Chromosomes; Y Chromosome; Genome
PubMed: 37267899
DOI: 10.1016/j.ajhg.2023.04.009 -
ZooKeys 2020The systematics of sitticine jumping spiders is reviewed, with a focus on the Palearctic and Nearctic regions, in order to revise their generic classification, clarify...
The systematics of sitticine jumping spiders is reviewed, with a focus on the Palearctic and Nearctic regions, in order to revise their generic classification, clarify the species of one region (Canada), and study their chromosomes. A genome-wide molecular phylogeny of 23 sitticine species, using more than 700 loci from the arachnid Ultra-Conserved Element (UCE) probeset, confirms the Neotropical origins of sitticines, whose basal divergence separates the Aillutticina (a group of five Neotropical genera) from the subtribe Sitticina (five genera of Eurasia and the Americas). The phylogeny shows that most Eurasian sitticines form a relatively recent and rapid radiation, which we unite into the genus Simon, 1868, consisting of the subgenera Simon, 1901 (seven described species), (41 described species), and Prószyński, 2017 (one species). Five species of occur natively in North America, presumably through dispersals back from the Eurasian radiation, but an additional three species were more recently introduced from Eurasia. Peckham & Peckham, 1883 is considered to be a full synonym of C. L. Koch, 1837 (not a distinct subspecies). Emerton, 1891 is removed from synonymy and recognized as a senior synonym of Chamberlin & Ivie, 1944. Thus, the five native in North America are , , , , and . The other sitticines of Canada and the U.S.A. are placed in separate genera, all of which arose from a Neotropical radiation including Simon, 1901 and F.O.Pickard-Cambridge, 1901: (1) Banks, 1905 (, , ), (2) (), and (3) Prószyński, 2017 (). All Neotropical and Caribbean "" are transferred to either (12 species total) or (14 species). (three species) and are both removed from synonymy with ; the synonymy of Prószyński, 1971 with Caporiacco, 1947 is restored; Caporiacco, 1947 is synonymized with . Six generic names are newly synonymized with and one with . Two Neotropical species are described as new, and Forty-six new combinations are established and three are restored. Three species synonymies are restored, one is new, and two are rejected. Across this diversity of species is a striking diversification of chromosome complements, with X-autosome fusions occurring at least four times to produce neo-Y sex chromosome systems (XXY and XXXY), some of which ( and ) are sufficiently derived as to no longer preserve the simple traces of ancestral X material. The correlated distribution of neo-Y and a base autosome number of 28 suggests that neo-Y origins occurred preferentially in lineages with the presence of an extra pair of autosomes.
PubMed: 32317852
DOI: 10.3897/zookeys.925.39691 -
Investigative Ophthalmology & Visual... May 2024We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies.
PURPOSE
We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies.
METHODS
We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non-ABCA4) inherited macular dystrophies (associated with BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3). BEST1 cases were subdivided into typical autosomal dominant and recessive disease. For PRPH2, only patients with variants at codons 172 or 142 were included. Recessive PROM1 and recessive RP1L1 cases were excluded because these variants give a more widespread or peripheral degeneration. The proportion of females was calculated for each condition; two-tailed binomial testing was performed. Where a significant imbalance was found, previously published cohorts were also explored.
RESULTS
Of 325 patients included, numbers for BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3 were 152, 35, 30, 50, 14, and 44, respectively. For autosomal dominant Best disease (n = 115), there were fewer females (38%; 95% confidence interval [CI], 29-48%; P = 0.015). For EFEMP1-associated disease (n = 35), there were significantly more females (77%; 95% CI, 60%-90%; P = 0.0019). No significant imbalances were seen for the other genes. When pooling our cohort with previous large dominant Best disease cohorts, the proportion of females was 37% (95% CI, 31%-43%; P = 1.2 × 10-5). Pooling previously published EFEMP1-cases with ours yielded an overall female proportion of 62% (95% CI, 54%-69%; P = 0.0023).
CONCLUSIONS
This exploratory study found significant sex imbalances in two autosomal macular dystrophies, suggesting that sex could be a modifier. Our findings invite replication in further cohorts and the investigation of potential mechanisms.
Topics: Humans; Female; Male; Sex Distribution; Macular Degeneration; Extracellular Matrix Proteins; Eye Proteins; Peripherins; Tissue Inhibitor of Metalloproteinase-3
PubMed: 38700873
DOI: 10.1167/iovs.65.5.9 -
National Science Review Feb 2023Assembly of a complete Y chromosome is a significant challenge in animals with an XX/XY sex-determination system. Recently, we created YY-supermale yellow catfish by...
Assembly of a complete Y chromosome is a significant challenge in animals with an XX/XY sex-determination system. Recently, we created YY-supermale yellow catfish by crossing XY males with sex-reversed XY females, providing a valuable model for Y-chromosome assembly and evolution. Here, we assembled highly homomorphic Y and X chromosomes by sequencing genomes of the YY supermale and XX female in yellow catfish, revealing their nucleotide divergences with only less than 1% and with the same gene compositions. The sex-determining region (SDR) was identified to locate within a physical distance of 0.3 Mb by F scanning. Strikingly, the incipient sex chromosomes were revealed to originate via autosome-autosome fusion and were characterized by a highly rearranged region with an SDR downstream of the fusion site. We found that the Y chromosome was at a very early stage of differentiation, as no clear evidence of evolutionary strata and classical structure features of recombination suppression for a rather late stage of Y-chromosome evolution were observed. Significantly, a number of sex-antagonistic mutations and the accumulation of repetitive elements were discovered in the SDR, which might be the main driver of the initial establishment of recombination suppression between young X and Y chromosomes. Moreover, distinct three-dimensional chromatin organizations of the Y and X chromosomes were identified in the YY supermales and XX females, as the X chromosome exhibited denser chromatin structure than the Y chromosome, while they respectively have significantly spatial interactions with female- and male-related genes compared with other autosomes. The chromatin configuration of the sex chromosomes as well as the nucleus spatial organization of the XX neomale were remodeled after sex reversal and similar to those in YY supermales, and a male-specific loop containing the SDR was found in the open chromatin region. Our results elucidate the origin of young sex chromosomes and the chromatin remodeling configuration in the catfish sexual plasticity.
PubMed: 36846302
DOI: 10.1093/nsr/nwac239 -
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