Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome.

OBJECTIVE: Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorly understood. This study focused on the neurological consequences of X-chromosome functional imbalances between sexes.
METHODS: Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated and contrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns and disease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus.
RESULTS: We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinically relevant genes in the context of rare genetic syndromes and brain waves modulation.
CONCLUSIONS: Considering female-specific patterns on brain transcriptional programs becomes essential when designing health care strategies for mental and sleep illnesses with sex bias in prevalence.

Many animal species exhibit sex-limited traits, where certain phenotypes are exclusively expressed in one sex. Yet, the genomic regions that contribute to these sex-limited traits in males and females remain a subject of debate. Reproductive traits are ideal phenotypes to study sexual differences since they are mostly expressed in a sex-limited way. Therefore, this study aims to use local correlation analyses to identify genomic regions and biological pathways significantly associated with male and female sex-limited traits in two distinct cattle breeds (Brahman [BB] and Tropical Composite [TC]). We used the Correlation Scan method to perform local correlation analysis on 42 trait pairs consisting of six female and seven male reproductive traits recorded on ~1,000 animals for each sex in each breed. To pinpoint a specific region associated with these sex-limited reproductive traits, we investigated the genomic region(s) consistently identified as significant across the 42 trait pairs in each breed. The genes found in the identified regions were subjected to Quantitative Trait Loci (QTL) colocalization, QTL enrichment analyses, and functional analyses to gain biological insight into sexual differences. We found that the genomic regions associated with the sex-limited reproductive phenotypes are widely distributed across all the chromosomes. However, no single region across the genome was associated with all the 42 reproductive trait pairs in the two breeds. Nevertheless, we found a region on the X-chromosome to be most significant for 80% to 90% (BB: 33 and TC: 38) of the total 42 trait pairs. A considerable number of the genes in this region were regulatory genes. By considering only genomic regions that were significant for at least 50% of the 42 trait pairs, we observed more regions spread across the autosomes and the X-chromosome. All genomic regions identified were highly enriched for trait-specific QTL linked to sex-limited traits (percentage of normal sperm, metabolic weight, average daily gain, carcass weight, age at puberty, etc.). The gene list created from these identified regions was enriched for biological pathways that contribute to the observed differences between sexes. Our results demonstrate that genomic regions associated with male and female sex-limited reproductive traits are distributed across the genome. Yet, chromosome X seems to exert a relatively larger effect on the phenotypic variation observed between the sexes.
Many livestock species show sexual differences between males and females. However, we still do not fully understand the specific area of the genome responsible for these differences. This study used a novel method to investigate this research question in two distinct tropically adapted cattle. The study found that the drivers of sexual differences are widely distributed across the animal’s genome, but the sex chromosome seems to play a large role. The genes within these regions are mostly protein-coding and regulatory genes. These genes were involved in biological processes that promote differences between males and females.

Biological factors and mechanisms that drive sex differences observed in sleep disturbances are understudied and poorly understood. The extent to which sex chromosome constitution impacts on sex differences in circadian patterns is still a knowledge void in the sleep medicine field. Here we focus on the neurological consequences of X-chromosome functional imbalances between males and females and how this molecular inequality might affect sex divergencies on sleep. In light of the X-chromosome inactivation mechanism in females and its implications in gene regulation, we describe sleep-related neuronal circuits and brain regions impacted by sex-biased modulations of the transcriptome and the epigenome. Benefited from recent large-scale genetic studies on the interplay between X-chromosome and brain function, we list clinically relevant genes that might play a role in sex differences in neuronal pathways. Those molecular signatures are put into the context of sleep and sleep-associated neurological phenotypes, aiming to identify biological mechanisms that link X-chromosome gene regulation to sex-biased human traits. These findings are a significant step forward in understanding how X-linked genes manifest in sleep-associated transcriptional networks and point to future research opportunities to address female-specific clinical manifestations and therapeutic responses.

UNASSIGNED: Analyze the relationship between changes in the proportion of X-chromosome deletions and clinical manifestations in children with Turner syndrome (TS).
UNASSIGNED: X-chromosome number abnormalities in 8,635 children with growth retardation were identified using fluorescence in situ hybridization (FISH). Meanwhile, the relationship between the proportion of X-chromosome deletions and the clinical manifestations of TS, such as face and body phenotype, cardiovascular, renal, and other comorbidities in children with TS was analyzed.
UNASSIGNED: A total of 389 children had X-chromosome number abnormalities, with an average age at diagnosis of 9.2 years. There was a significant increase in diagnoses around the ages of 3 and 7 years and highest number of diagnoses at 10 years of age. 130 with XO (complete loss of an X-chromosome), 205 with XO/XX, 8 with XO/XXX, 23 with XO/XX/XXX, 19 with XO/XY, and 4 with XO/XY/XYY. Body and facial phenotypes increased with higher mosaicism proportions, with a relatively high correlation shown with Pearson correlation analysis (r = 0.26, p = 1.7e-06). The incidence of congenital heart malformations was 25.56%, mainly involving a bicuspid aortic valve, and were more common in patients who had complete loss of an X-chromosome. However, this relationship was not present for renal disease (p = 0.26), central nervous system, thyroid, or liver disease.
UNASSIGNED: The mosaicism (XO/XX) is the most common karyotype of TS in screened cases. The phenotypes in children with TS may increase with the proportion of X-chromosome deletions, but the renal disease and comorbidities did not show the same characteristics.

Population genetic inference of selection on the nucleotide sequence level often proceeds by comparison to a reference sequence evolving only under mutation and population demography. Among the few candidates for such a reference sequence is the 5\' part of short introns (5SI) in Drosophila. In addition to mutation and population demography, however, there is evidence for a weak force favouring GC bases, likely due to GC-biased gene conversion (gBGC), and for the effect of linked selection. Here, we use polymorphism and divergence data of Drosophila melanogaster to detect and describe the forces affecting the evolution of the 5SI. We separately analyse mutation classes, compare them between chromosomes, and relate them to recombination rate frequencies. GC-conservative mutations seem to be mainly influenced by mutation and drift, with linked selection mostly causing differences between the central and the peripheral (i.e., telomeric and centromeric) regions of the chromosome arms. Comparing GC-conservative mutation patterns between autosomes and the X chromosome showed differences in mutation rates, rather than linked selection, in the central chromosomal regions after accounting for differences in effective population sizes. On the other hand, GC-changing mutations show asymmetric site frequency spectra, indicating the presence of gBGC, varying among mutation classes and in intensity along chromosomes, but approximately equal in strength in autosomes and the X chromosome.

The present study aimed to contribute to the limited research on buffalo (Bubalus bubalis) semen traits by incorporating genomic data. A total of 8465 ejaculates were collected. The genotyping procedure was conducted using the Axiom® Buffalo Genotyping 90 K array designed by the Affymetrix Expert Design Program. After conducting a quality assessment, we utilized 67,282 SNPs genotyped in 192 animals. We identified several genomic loci explaining high genetic variance by employing single-step genomic evaluation. The aforementioned regions were located on buffalo chromosomes no. 3, 4, 6, 7, 14, 16, 20, 22, and the X-chromosome. The X-chromosome exhibited substantial influence, accounting for 4.18, 4.59, 5.16, 5.19, and 4.31% of the genomic variance for ejaculate volume, mass motility, livability, abnormality, and concentration, respectively. In the examined genomic regions, we identified five novel candidate genes linked to male fertility and spermatogenesis, four in the X-chromosome and one in chromosome no. 16. Additional extensive research with larger sample sizes and datasets is imperative to validate these findings and evaluate their applicability for genomic selection.

The COVID-19 pandemic has uncovered many mysteries about SARS-CoV-2, including its potential to trigger abnormal autoimmune responses. Emerging evidence suggests women may face higher risks from COVID-induced autoimmunity manifesting as persistent neurological symptoms. Elucidating the mechanisms underlying this female susceptibility is now imperative. We synthesize key insights from existing studies on how COVID-19 infection can lead to immune tolerance loss, enabling autoreactive antibodies and lymphocyte production. These antibodies and lymphocytes infiltrate the central nervous system. Female sex hormones like estrogen and X-chromosome mediated effects likely contribute to dysregulated humoral immunity and cytokine profiles among women, increasing their predisposition. COVID-19 may also disrupt the delicate immunological balance of the female microbiome. These perturbations precipitate damage to neural damage through mechanisms like demyelination, neuroinflammation, and neurodegeneration - consistent with the observed neurological sequelae in women. An intentional focus on elucidating sex differences in COVID-19 pathogenesis is now needed to inform prognosis assessments and tailored interventions for female patients. From clinical monitoring to evaluating emerging immunomodulatory therapies, a nuanced women-centered approach considering the hormonal status and immunobiology will be vital to ensure equitable outcomes. Overall, deeper insights into the apparent female specificity of COVID-induced autoimmunity will accelerate the development of solutions mitigating associated neurological harm.

Genes on the X-chromosome are extensively expressed in the human brain. However, little is known for the X-chromosome\'s impact on the brain anatomy, microstructure, and functional network. We examined 1,045 complex brain imaging traits from 38,529 participants in the UK Biobank. We unveiled potential autosome-X-chromosome interactions, while proposing an atlas outlining dosage compensation (DC) for brain imaging traits. Through extensive association studies, we identified 72 genome-wide significant trait-locus pairs (including 29 new associations) that share genetic architectures with brain-related disorders, notably schizophrenia. Furthermore, we discovered unique sex-specific associations and assessed variations in genetic effects between sexes. Our research offers critical insights into the X-chromosome\'s role in the human brain, underscoring its contribution to the differences observed in brain structure and functionality between sexes.

UNASSIGNED: The insertion/deletion polymorphism (InDel), an ideal forensic genetic marker with a low spontaneous mutation rate and small amplification product fragments, is widely distributed in the genome, combining the advantages of STR and SNP genetic markers. The X-chromosome has high application value in complex paternity testing, and it is an excellent system for evaluating population admixture and studying evolutionary anthropology. However, further research is needed on the population genetics of X-chromosome InDels (X-InDels).
UNASSIGNED: In this article, a system composed of 38 X-InDel loci was utilized to analyse and evaluate the forensic parameters of the Guizhou Han population in order to explore its forensic application efficiency.
UNASSIGNED: The results showed that expected heterozygosities spanned from 0.0189 to 0.5715, and the cumulative power of discrimination of the 32 X-InDels and three linkage blocks was 0.9999999954 and 0.999999999999741 for males and females, respectively. The combined mean exclusion chance of these loci for trios and duos is 0.999999 and 0.999747, respectively. Multiple methods like principal component analysis, Fst genetic distance, and phylogenetic reconstruction were employed for dissecting the genetic structure of the Guizhou Han population by comparing it with previously reported populations. As expected, the studied Han population displayed relatively close genetic affinities with the East Asian populations. At the same time, there were obvious genetic differentiations between the Guizhou Han population and other continental populations that were discerned, especially for the African populations.
UNASSIGNED: This study further verified the applicability of 38 X-InDels for human personal identification and kinship analyses of Han Chinese, and also showed the application potential of X-InDels in population genetics.