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The Gene

Key Components:
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  • Gene Name: DNA damage recognition and repair factor
  • Official Symbol - XPA
    • ​Other symbols- XP1, XPAC
  • NCBI Gene ID: 7507
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Links to Isoforms Described in Detail:
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  • NCBI RefSeq Nucleic Acid (RNA sequence)(41): NR_149091.1
  • NCBI RefSeq Nucleic Acid (RNA sequence)(42): NR_149092.1
  • NCBI RefSeq Nucleic Acid (RNA sequence)(43): NR_149093.1
  • NCBI RefSeq Nucleic Acid (RNA sequence)(44): NR_149094.1
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant c
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant d
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant e
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant f
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant g
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant h
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant i
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant j
  • NCBI RefSeq Nucleic Acid (AceView mRNA): variant k
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The following information in regards to exon and intron length as well as locations in the proceeding tables was obtained from Aceview. Both variants 'a' and 'b' are the isoforms examined in detail. The following links for the two isoforms will bring the viewer to the homage of the gene. In order to select the desired isoform, please click on either 'a' or 'b' next to the title "mRNA" at the top of the page.
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  • Isoform a (Protein coding mRNA) AceView (3): Variant a
  • Isoform b (Non-coding RNA) AceView (3): Variant b 
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Table 1. Gene Table for Isoform Variants a and b
Table 1: This table compares both the genomic nucleic acid sequence numbers on the local gene as well as its overall genomic location for two isoforms of XPA; variants 'a' and 'b'. All of the information that is provided in this table in regards to exon and intron length has been obtained from AceView(3). The XPA gene is 22,500 bp long, and has 11 total isoforms. Only one of these isoforms, variant 'a', is a protein coding mRNA. Variant 'b' shown in this table is a non-coding RNA. Both variants 'a' and 'b' shared the same pre-mRNA length of 22,500 bp, allowing for the Transcription Start Site (TSS) to be represented as '1' for each. This information, along with the locations for the TATA Box, Initiator, GC Box, and CCATT Box, were obtained from EPD(2). The last major difference between each of the isoforms is seen in their number of exons and introns. The protein coding variant 'a' has 6 exons, whereas the non protein-coding variant 'b' has 7 exons. This information has been illustrated into diagram 1 seen below.
Diagram 1. Gene Diagram Based on Variants a and b
Created using Adobe Photoshop 2020
Diagram1.jpg
Diagram 1: The information shown in this diagram has been provided by the data in Table 1. The table shown above represents a comparison between variants 'a' and 'b'. Information regarding their exon and intron length, as well as Poly-A-site and Poly-A-signal were obtained from AceView(3). The information for the promoter region represented as the blue box in the above diagram was obtained from EPD(2). Differences between variants 'a' and 'b' are very minimal.  They share the same promoter region due to the similarity of their genomic location, 100,459,691 … 100,437,192. The major difference between variants 'a' and 'b' are seen by the alternative exon 6 shown as the yellow box for variant b, the position is shown at 14,980 bp ... 15,210 bp. This would make the subsequent intron 15,211 bp ... 21,822 bp. Variant 'a' exon 6 and variant 'b' exon 7 are now represented at the same positions of 21,822 bp … 22,500 bp.
Table 2. Isoforms a and b Composite Table
Table 2: This table shows a comparison between sequences of the pre-mRNA isoforms variants 'a' and 'b' obtained from AceView(3). The table starts the comparison with the 3' UTR because the 5' end is incomplete resulting in no 5' UTR present on either of the two isoforms. The 3' UTR of the protein coding variant 'a' spanned from 21,972 ... 22,500, whereas variant 'b' was from 21,714 ... 22,500. Variant 'a' contains 6 exons whereas variant 'b' contains 7 exons. Both variants 'a' and 'b' contain an XPA protein C-terminus, XPA protein N-terminus, and a coiled coil stretch. Neither of the two variants contain a signal peptide. Variant 'a' has a predicted protein of 312 amino acids and variant 'b' has a slightly smaller predicted protein of 303 amino acids. Each of the variants are compared in Diagram 2 and Diagram 3 respectively.
Diagram 2. Variant a pre-mRNA
Created using Adobe Photoshop 2020
Diagram2NEW.jpg
Diagram 3. Variant b pre-mRNA
Created using Adobe Photoshop 2020
Diagram3Official.jpg
Diagrams 2 and 3: The diagrams shown above represent a comparison between variants 'a' and 'b'. All of the information used to make these two diagrams is shown in Table 2 and obtained from AceView(3). These two isoforms were chosen over the other nine isoforms because variant 'a' was a protein coding isoform, and variant 'b' was the largest non-coding RNA. Each of these variants also had the longest predicted proteins as well as a CDS that was very similar. The CDS for both variants spans nearly the entire length of the pre-mRNA's with variant 'a' spanning from 1 ... 21,972 and variant 'b' from 1 ... 21,822. Both variants also share the same Poly-A-signal and Poly-A-site. Variant 'a' contains 6 exons whereas variant 'b' contains 7 exons. The functional domains and 3' UTR are very similar but not exact in location as well between the two variants allowing for a more accurate comparison.
Table 3. Comparison of all Isoforms
Table 3: The DNA damage recognition and repair factor XPA has 11 different isoforms shown in the table above obtained from AceView(3). There are many differences between the isoforms, such as number of exons and introns, as well as CDS length. The protein coding variant 'a' had the largest CDS of 939 bp, although it did not have as many exons as variant 'b' which had 7, variant 'b' had a CDS shorter than variant 'a' of 912 bp. This observation shows that the number of exons does not necessarily reflect the CDS length of an isoform. This table also shows the presence of a 5' UTR in variants 'd', 'e', 'h', 'i', 'j', and 'k'. The only isoform that does not have a complete 3' end is variant 'e'. Variant 'e' is also the only isoform along with variants 'a' - 'c' that contains a functional domain. This may be be due to the amount of exons each variant has and their level of expression. They all contain 4 or more exons, whereas all of the other isoforms are only 2 exons or less.
Table 4. Tissue Expression in all Isoforms
Table 4: The XPA Gene is a DNA damage recognition and repair factor that has a very large impact on nearly all major tissues of the body expressed by 10 of the 11 isoforms. Table 4 shows the tissue expression from each isoform as given by AceView(3). The expression from each of the isoforms shows a pattern for the type of tissue that they effect. Many of the variants show a constant expression throughout various physiological states such as the whole embryo being effected in variants 'h' and 'i'. The fetal liver, heart, and eyes are tissues expressed by variants 'b', 'f', 'g', and 'i'. These variants as well as many others show strong associations with various types of tumor growth and cancerous tissue which explains the many forms of tissue effected. The physiological state of cancer from the XPA gene is seen in variant 'b' with cancerous tissue of the mammary glands. Tumor growth is expressed in half of the tissue expressing isoforms; variants 'b', 'd', 'g', 'i', and 'j'. These variants show tumor growth such as tumor tissue of the tongue and colon.
Development Related Differential Gene Expression
Gene expression at various developmental periods are expressed from XPA mainly in the urinary bladder and reproductive organs according to information gathered from Ensemble(40). Gene expression as early as 7 weeks is shown in both the urinary bladder and reproductive organs with an expression level of 52 TPM and 44 TPM respectively. From 7-7.5 weeks, there is expression shown in the urinary bladder with an expression level of 37 TPM, and 58 TPM at 7.5 weeks. At 8 weeks the urinary bladder and reproductive organs show an expression level of 42 TPM and 43 TPM respectively. The reproductive organs are consistent with that level of expression through week 9, but the urinary bladder rises in expression levels to 50 TPM. At week 10, the reproductive organs show an expression level of 42 TPM.
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