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- Table of Contents
Facts about Alpha-crystallin A chain.
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Human | |
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Gene Name: | CRYAA |
Uniprot: | P02489 |
Entrez: | 1409 |
Belongs to: |
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small heat shock protein (HSP20) family |
AlphaA Crystallin; CRYA1; CRYA1crystallin, alpha-1; CRYAA; crystallin, alpha A; Heat shock protein beta-4; HSPB4; HSPB4alpha-crystallin A chain; human alphaA-crystallin (CRYA1), 10HspB4
Mass (kDA):
19.909 kDA
Human | |
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Location: | 21q22.3 |
Sequence: | 21; NC_000021.9 (43169008..43172810) |
Expressed in eye lens.
Cytoplasm. Nucleus. Translocates to the nucleus during heat shock and resides in sub-nuclear structures known as SC35 speckles or nuclear splicing speckles.
In this article, we discuss the Data Analysis Pipeline Developed By David Scott and Josh Weinstein. We describe the Methods, Results, and Conclusions. Using this pipeline, you can easily find out what data your clones are missing. The next time you need to perform a cloning study, read this article! You'll learn everything you need to know about Boster Bio.
The Data Analysis Pipeline developed by David Scott and Josh Weinstein was designed to quickly handle the heavy lifting of image processing for astronomical data. The template pipeline spans the entire observing planning process, from identifying imaging goals to publishing results. The pipeline also encapsulates all policy and processing decisions in a standardized, auditable framework. This paper will introduce the technical details of the pipeline's processing environment and serve as a valuable teaching environment for astronomical data management.
The aA-crystallin gene, CRYAA, is flanked by D21S212 and D21S171 on chromosome 21q. We screened the coding regions for mutations associated with ADCC by using PCR primers designed from a partial genomic sequence and full-length cDNA sequence. Figure 2 shows the primer locations and PCR products. The sequences of the PCR products were compared directly to published sequences. Exons 1 and 2 of the CRYAA gene were found to be identical to previously published sequences.
Knockdown of the KLF10 gene partially rescued the transcriptional activity of CRYAA with the rs7278468 T allele but had no effect on the G allele. Because the T allele is associated with ARC, it increases the binding affinity of KLF-10 to CRYAA promoter. Therefore, knocking down KLF-10 reduces CRYAA transcription. As a result, a reduction of KLF10 could protect against ARC.
The sequence analysis of CRYAA revealed a mutation in exon 3 that causes a missense mutation at codon 116. This mutation changes the amino acid Arginine to Histidine and is present only in affected family members. The same mutation was absent in unaffected family members and in control individuals. This finding strongly indicates that the mutation is a causative one and that the CRYAA gene is not caused by benign SNPs located in linkage disequilibrium with the cataract gene.
As we know, the CRYAA gene is highly expressed in the lens and is essential for lens development and maintenance. Mice with CRYAA knockout develop a lens that is smaller and has opacities in its nucleus. These mice also develop a total cataract. The presence of dense inclusion bodies in light microscopy is sufficient evidence to link this mutation to progressive cataracts. It is also suspected that the CRYAA gene is involved in some forms of age-related macular degeneration.
The CRYAA gene contains three SNPs in the promoter region, two of which are present in both zebra fish and humans. The diamonds represent the pair-wise comparison of the two SNPs. The red shading in these squares represents higher values of D'; maximum D' is 100%. To test this hypothesis, the CRYAA gene was sequenced and analyzed in a human and zebra fish population.
The CRYAB and GFAP markers colocalized in the gray-white matter transition region. Double labeling microphotographs using a 40x/1.3 objective lens showed a CRYAB-positive cell within layer V of the cerebral cortex. This result was also confirmed by immunohistochemistry. Nevertheless, this data suggests that CRYAB may not be a reliable marker of the degree of damage within a TBI sector.
The most prominent effect of rs7278468 on CRYAA transcriptional activity was found in the gene's binding motif to the repressor KLF10. Knockdown of KLF10 partially rescued the phenotypic activity of CRYAA. Knocking down KLF10 had no effect on CRYAA transcriptional activity. However, this gene is not functionally expressed in humans.
In mice, the C-G-T haplotype is associated with increased risk of ARC and cortical cataract. The C-G-T haplotype is associated with decreased transcription activity of CRYAA. This effect is consistent across all three haplotypes of CRYAA. During aging, CRYAA levels rise in the lens. These findings support the concept that CRYAA plays an important role in ARC development.
The transcription activity of the CRYAA gene was significantly decreased when the G allele was replaced with the T allele. This effect was particularly significant in the HLE cell line. Furthermore, the T-C-T haplotype decreased the transcription activity of the CRYAA gene by 17%. Hence, it is important to know the genetic variants that control CRYAA expression. Listed below are the conclusions from these studies.
The T allele, rs7278468, affected transcriptional activity of the CRYAA gene. This allele is located within the binding motif of the transcriptional repressor KLF10. A single-base change from the G to the T allele enhanced the binding affinity of KLF10 and inhibited transcription of CRYAA. In addition, a knockdown of KLF10 partially rescued the transcriptional activity of CRYAA.
The CRYAA gene promoter region contains three SNPs that are associated with ARC. The C-G-T haplotype is associated with a greater risk for ARC, while the T-C-G haplotype is protective. The rs7278468 T allele reduces transcriptional activity. Furthermore, the T allele increases binding of KLF10 to the CRYAA promoter, which inhibits CRYAA transcription.
Previous studies implicated that SNP haplotypes in the CRYAA promoter regulate the transcriptional activity of the gene. Hence, site-directed mutagenesis was performed to change individual SNPs from the protective haplotype to the risk haplotype. Transfection of cells containing the CRYAA promoter resulted in a 10 fold increase in luciferase activity compared with controls.
Despite the promising results, more research is needed to confirm the association between these two genes and ARC. Larger sample sizes are required to validate this association, but further research could focus on the associations of these SNPs with cataracts. However, the G allele of rs7278468 strengthened the Sp1 binding affinity. In addition, the rs7278468 gene is highly associated with ARC in Northern Italian patients.
The CRYAA marker is a candidate gene for a rare genetic disease. Its promoter region contains three single nucleotide polymorphisms (SNPs) that are associated with ARC. The C-G-T haplotype seems to be a risk factor for ARC, while the T-C-G haplotype is protective. The C-G-T haplotype is largely protective, although the T allele is responsible for reduced transcriptional activity of the CRYAA promoter. The T allele increases KLF10 binding, which inhibits CRYAA transcription.
The three SNPs in the promoter region of the CRYAA gene are shown in Figure 2. The coloured squares represent pairwise comparisons of two SNPs. The red shading indicates higher D' values. The maximum D' is 100%. This mutational pattern is unusual for ocular disorders. It may also play a role in rare eye diseases such as myopia. Further research is needed to determine the role of CRYAA in human eye disease.
The CRYA1 gene was found in the band 21q22.3, where it was found to be in close proximity to fifteen other genes. Other DNA markers in the band are shown as dotted lines. The CRYA1 gene was assigned to the chromosome 21q22.3, so its location relative to these genes was confirmed. The CRYA1 gene is present in both the sexes, but the CryAA gene is not in every cell type.
The rs7278468 T allele affects the binding of KLF10 to the CRYAA promoter. This mutation increases the susceptibility to ARC. Further research is needed to determine the role of KLF10 in CRYAA expression. In addition to its effect on CryAA expression, the CRYAA gene also contributes to the development of neurodegenerative diseases, such as Alzheimer's disease and schizophrenia.
PMID: 817940 by de Jong W.W., et al. The amino acid sequence of the A chain of human alpha-crystallin.
PMID: 8587135 by Jaworski C.J.; A reassessment of mammalian alpha A-crystallin sequences using DNA sequencing: implications for anthropoid affinities of tarsier.