China
Africa
Explore chapters and articles related to this topic
Statistics for Genomics
Published in Altuna Akalin, Computational Genomics with R, 2020
In biology and many other fields, data is collected via experimentation. The nature of the experiments and natural variation in biology makes it impossible to get the same exact measurements every time you measure something. For example, if you are measuring gene expression values for a certain gene, say PAX6, and let’s assume you are measuring expression per sample and cell with any method (microarrays, rt-qPCR, etc.). You will not get the same expression value even if your samples are homogeneous, due to technical bias in experiments or natural variation in the samples. Instead, we would like to describe this collection of data some other way that represents the general properties of the data. Figure 3.1 shows a sample of 20 expression values from the PAX6 gene.
Epidemiology and genetic associations of neonatal tumors
Published in Prem Puri, Newborn Surgery, 2017
Further, genetic pathways have also been reported. An association between the WNT/beta-catenin signaling pathway (the CTNNB1 gene, encoding beta-catenin) is also known.124,125 This suggests that Wnt signaling pathway dysregulation also plays an oncogenic role in certain WTs. Further, genomic gain of the proto-oncogene transcription factor gene MYCN is associated with anaplasia and a decreased relapse-free and overall survival, independent of the histologic findings.126 In addition, a LOH for 16q is a structural alteration identified in 20%–30% of WTs, and p53 alteration also appears to be required for the progression to the anaplastic subtype. Further, associations with p53 analogues (p73 and p63/KET) suggest that association with the p53 family may be important to cell growth and differentiation.127 Haploinsufficiency in the PAX6 gene is also strongly associated with aniridia and may be involved.128
Genetics of Wilms tumor
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
Mathias A.E. Frevel, Bryan R.G. Williams
The association with the WAGR syndrome is observed in only a small subset of Wilms tumor cases (1–2%). These patients carry constitutional deletions of band 11p13. Two cloned genes from this locus are known to be responsible for parts of the WAGR phenotype. Aniridia, which is fully penetrant, has been linked to mutations in the PAX6 gene that is involved in eye differentiation (Ton et al., 1991). Wilms tumor, which develops in only 30–50% of aniridia patients, and the genito-urinary abnormalities are caused by the disruption of the WT1 gene, a transcription factor that plays a pivotal role in both genital and renal development. For the genito-urinary abnormalities to occur a single mutant WT1 allele is sufficient, whereas the remaining WT1 allele has been shown to carry tumor-specific mutations in most WAGR patients conforming to the ‘two-hit’ hypothesis (Pritchard-Jones, 1997).
miR-130a-3p Enhances the Chemosensitivity of Y79 Retinoblastoma Cells to Vincristine by Targeting PAX6 Expression
Published in Current Eye Research, 2022
Xiulan Lu, Huifang Tu, Dongrun Tang, Xiaoming Huang, Fengyuan Sun
Subsequently, we sought to determine the target genes of miR-130a-3p in regulating the chemosensitivity of RB cells. Targetscan website (http://targetscan.org/vert_71/) predicted that miR-130a-3p had a binding site with PAX6, and dual-luciferase assay confirmed that miR-130a-3p could specifically bind PAX6. PAX6 mutation causes eye defects and neurological abnormalities associated with structural alterations in the brain.24 PAX6 silencing represses growth and facilitates apoptosis of cultured human RB cells.40 Also, PAX6 is reported to regulate the chemoresistance of glioblastoma stem cells to temozolomide.41 Consequently, we speculated that miR-130a-3p affected the chemosensitivity of RB cells by targeting PAX6. This study exhibited that PAX6 expression was significantly elevated in RB tissues compared with that in the normal retinal tissues. PAX6 expression in the VCR-resistant tissues and cells was also notably upregulated. PAX6 expression was reduced in Y79/VCR cells transfected with miR-130a-3p mimic. Briefly, miR-130a-3p targeted PAX6 expression in VCR-resistant RB cells. Functional rescue experiments verified that overexpression of PAX6 attenuated the promoting effect of miR-130a-3p on the chemosensitivity of RB cells. Moreover, the murine model of RB was established and the model mice underwent VCR treatment. Our results confirmed that overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo by targeting PAX6 expression.
Missense mutation in the PAX6 gene can cause a complex mild variable phenotype predominated by concomitant strabismus
Published in Ophthalmic Genetics, 2022
Tao Shen, Xuan Qiu, Xiaoming Lin, Jing Lin, Xiuling Li, Qiwen Chen, Liuqing Pan, Zhonghao Wang, Huangxuan Shen, Qingjiong Zhang, Jianhua Yan
In conclusion, our study demonstrated that familial concomitant strabismus complicated by mild ocular phenotypes can be caused by a PAX6 mutation. PAX6 mutations may be associated with various phenotypes of ocular developmental defects, and some of them can be easily under-recognized in clinical practice. We recommend considering PAX6 as a candidate gene in the diagnostic screen for familial concomitant strabismus in order to avoid missed diagnosis of the mild ocular abnormalities. Most of the patients with typical concomitant strabismus have normal visual acuity; therefore, ophthalmologists must have a high index of suspicion for other ocular abnormalities when observing undiagnosed visual loss in patients with concomitant strabismus, especially when characterized with familial clustering. Careful examinations of mild ocular phenotypes are necessary for an accurate diagnosis of varied ocular abnormalities in families with PAX6 mutations, and proper diagnosis can facilitate genetic and clinical counseling for affected patients.
Genetic causes of nystagmus, foveal hypoplasia and subnormal visual acuity- other than albinism
Published in Ophthalmic Genetics, 2021
Miriam Ehrenberg, Laura Bagdonite-Bejarano, Anne B. Fulton, Naama Orenstein, Claudia Yahalom
Defects in the PAX6 gene affect embryonal eye development and result in a range of clinical phenotypes, the most common being aniridia, a panocular disorder characterized by iris hypoplasia combined with foveal hypoplasia. Aniridia is associated with other, typically later-onset ocular abnormalities, including cataract, glaucoma, and keratopathy (16). Infrequently, deletions present both in the PAX6 and its neighbor gene WT1. The resultant phenotype, known as WAGR syndrome, is characterized by a life-threatening kidney tumor, in addition to the abovementioned ophthalmic findings. Hence, early identification of this gene mutation is important. Milder forms of PAX6- related eye disease have been described (17). These are noted by only mild anterior segment dysgenesis such as corectopia (accompanied by foveal hypoplasia and nystagmus), isolated transillumination defects or even by only isolated foveal hypoplasia and nystagmus (17,18). In our study, 33% of the individuals in the PAX6 group had corectopia as the sole anterior segment sign. The others had additional anterior segment dysgenesis such as cataract or iridolental strands. These helped lead to the suspicion of PAX6 as the causative gene. Though mild, the anterior segment changes prompted the treating clinicians to sequence the PAX6 genes before broadening the work-up with an ERG exam. This may explain the significantly lower proportion of patients in the PAX6- group that had undergone an ERG exam: 20% compared to 71% of those in both SLC38A8 and diverse gene mutation groups.