Involvement of X-chromosome Reactivation in Augmenting Cancer Testis Antigens Expression:A Hypothesis

Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

ALLELE DISTRIBUTION OF FIVE X-CHROMOSOME SHORT TANDEM REPEAT LOCI IN EWENKE POPULATION OF NORTH CHINA

Objective To study the allele genetic polymorphism of five short tandem repeat （STR） loci on X-chromosome in Ewenke population of north China and to provide basic data for forensic identification. Methods Genomic DNA was extracted from EDTA-whole blood of Ewenke population by Chelex-100. The DNA samples were amplified by PCR and were analyzed by polyacrylamide gel electrophoresis and silver staining. The sequence length variations of DXS6799, DXS8378, DXS101, HPRTB, and DXS6789 loci on X-chromosome in 98 unrelated Ewenke individuals were investigated. Results All five loci analyzed showed high polymorphism and genetic stability. The data of the five X-chromosome STR loci in Ewenke ethnic group of China was in accordance with Hardy-Weinberg equilibrium by Chi-square test. Conchusion Allele polymorphism of five X-chromosome STR loci can be used as a genetic marker for forensic identification and population genetic research.

Fine-scale evolutionary genetic insights into Anopheles gambiae X-chromosome

Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the model malaria vector, Anopheles gambiae and to use the information in other species of local importance, we scanned the published X-chromosome se-quence for detail characterization and obtain evolutionary status of different genes. The te-locentric X-chromosome contains 106 genes of known functions and 982 novel genes. Majori-ties of both the known and novel genes are with introns. The known genes are strictly biased towards less number of introns;about half of the total known genes have only one or two in-trons. The extreme sized (either long or short) genes were found to be most prevalent (58% short and 23% large). Statistically significant positive correlations between gene length and intron length as well as with intron number and intron length were obtained signifying the role of introns in contributing to the overall size of the known genes of X-chromosome in An. gam-biae. We compared each individual gene of An. gambiae with 33 other taxa having whole ge-nome sequence information. In general, the mosquito Aedes aegypti was found to be ge-netically closest and the yeast Saccharomyces cerevisiae as most distant taxa to An. gambiae. Further, only about a quarter of the known genes of X-chromosome were unique to An. gambiae and majorities have orthologs in dif-ferent taxa. A phylogenetic tree was constructed based on a single gene found to be highly orthologous across all the 34 taxa. Evolutionary relationships among 13 different taxa were in-ferred which corroborate the previous and pre-sent findings on genetic relationships across various taxa.

Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome

Stroke is the second leading cause of death and a major cause of disability worldwide,and biological sex is an important determining factor in stroke incidence and pathology.From childhood through adulthood,men have a higher incidence of stroke compared with women.Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke.Autophagy is a self-degrading cellular process orchestrated by multiple core proteins,which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy vesicles fuse with lysosomes or endosomes.The levels and the activity of components of these signaling pathways and of autophagy-related proteins can be altered during ischemic insults.Ischemic stroke activates autophagy,however,whether inhibiting autophagy after stroke is beneficial in the brain is still under a debate.Autophagy is a potential mechanism that may contribute to differences in stroke progression between the sexes.Furthermore,the effects of manipulating autophagy may also differ between the sexes.Mechanisms that regulate autophagy in a sex-dependent manner in ischemic stroke remain unexplored.In this review,we summarize clinical and pre-clinical evidence for sex differences in stroke.We briefly introduce the autophagy process and summarize the effects of gonadal hormones in autophagy in the brain and discuss X-linked genes that could potentially regulate brain autophagy.Finally,we review pre-clinical studies that address the mechanisms that could mediate sex differences in brain autophagy after stroke.

Study on the extra X chromosome＇s effect on the hormone level of Klinefelter＇s syndrome

Klinefelter＇s syndrome is an inherited （genetic） disorder found only in men caused by at least one extra X chromosome in a cell. Does the extra X chromosome have any effect on the hormone level of Klinefelter＇s Syndrome？ In this paper, 25 subjects with Klinefelter＇s syndrome, 30 infertile subjects and 36 normal men without Klinefelter＇s syndrome were compared each other in endocrinology profile and cytogenetics. Subjects with Klinefelter＇s syndrome were identified by the karyotypes 47, XXY or 47, XXY/46XY, and positive of the X-chromatins （Barr bodies）. Hormone analysis of subjects with Klinefelter＇s syndrome showed that the testosterone （T） values were lower than those of the normal subjects, while the FSH and LH values were higher than those of the normal people; in the infertile experiment subjects without Klinefelter＇s Syndrome, the karyotypes are 46, XY, with negative of the X-chromatins. The testosterone （T） values of these subjects were also lower than those of the normal people, but the FSH and LH values were within the normal range. These results indicated that endocrinological test on infertile subjects can be used to determine whether a cytogenetic analysis is necessary, and hence exclude non- Klinefelter＇s syndrome. The mechanism of the occurrence of this difference, its clinical applications and the relationship among the karyotypes, the endocrinological test and the severity of the phenotype are discussed. Lyon＇s hypothesis stating that only one of the two X-chromosomes is genetically active in female cells, but our study concluded that the extra X chromosome do have effect on the hormone level of Klinefelter＇s Syndrome.

Analysis of Linkage for Ten X-STR Markers in a Rio de Janeiro(Brazil)Three-Generation Family Sample

Recently, typing of polymorphisms on the X chromosome has become a standard technique in forensic genetics and a growing number of short tandem repeats (STR) has been established in this chromosome related to genetic population studies. Knowledge of marker recombination is very important especially when the X chromosome typing is used in forensic kinship analysis. It is known that the meiotic recombination is not a simple function of the physical distance between segments of the DNA but the recombination events between them tend to be clustered at special regions of the chromosome. Information on the rate of recombination among markers can be gathered by studying families through several generations. In this work we have typed DNA samples of pedigree consisting of nineteen families in Rio de Janeiro, constituted of grandfather, mother and grandson, and in some cases grandmother and aunt, and reported the recombination of 10 STR markers of the X chromosome. The study of the linkage analysis using the LOD score has shown that the marker pairs DXS8378-DXS7423, DXS7132-DXS9898, DXS7132-GATA172D05 DXS9898-DXS7133 and DXS6809-DXS7133 are not transmitted in a random way, during a recombination event.

Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease

Background:Heterotaxy(HTX)is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease(CHD).The aim of this study was to analyze rare copy number variations(CNVs)in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods:Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients,and available samples from parents were used to confirm the inheritance pattern.Potential candidate genes in CNVs region were prioritized via the DECIPHER database,and PNPLA4 was identified as the leading candidate gene.To validate,we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model,followed by a series of transcriptomic,biochemical and cellular analyses.Results:Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients(12.5%).Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort,and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD.PNPLA4 is expressed in the lateral plate mesoderm,which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation,and in the neural crest cell lineage.Through a series of in vivo and in vitro analyses at the molecular and cellular levels,we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production.Conclusions:Our findings demonstrated a significant association between CNVs and HTX/CHD.Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Genetic polymorphism analyses of a novel panel of 19 X-STR loci in the Chinese Uygur ethnic minority

The population genetic data and forensic parameters of 19 X-chromosome short tandem repeat （X-STR） loci in Chinese Uygur ethnic minority are presented. These loci were detected in a sample of 233 （94 males and 139 females） unrelated healthy individuals. We observed 238 alleles at the 19 X-STR loci, with the corresponding gene frequencies spanning the range from 0.0021 to 0.5644. After Bonferroni correction （P〉0.0026）, there were no signif- icant deviations from Hardy-Weinberg equilibrium. The cumulative power of discrimination in females and males, and the probability of exclusion of the 19 X-STR loci were 0.999 999 999 999 999 999 998 091,0.999 999 999 999 966, and 0.999 999 986 35, respectively. The cumulative mean exclusion chance was 0.999 999 992 849 in deficiency cases, 0.999 999 999 999 628 in normal trios, and 0.999 999 998 722 in duo cases. The high value of the forensic parameters mentioned above revealed that the novel panel of 19 loci had important values for forensic applications in the LJygur group.