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News & Updates

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ALDH Overview

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ALDH Gene Superfamily

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Vasiliou Laboratory

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News & Updates


Exon Duplication in Rattus norvegicus ALDH3B2.
ALDH Servers Back Online!
The Missing Link Found! Rattus norvegicus ALDH4A1
New Record Feature Added : Alternative Splice Variants
Aldehyde Dehydrogenase Enzyme Kinetics for Substrates and Inhibitors Section Incorporated
ALDH Molecular Features Section Revised
Aldehyde Dehydrogenase, Alcohol Use, and Flushing / Hives
ALDH.ORG Version 3 Released!
ALDH Database Revision - Murine Aldh1a7 and Aldh1a4
Welcome to WWW.ALDH.ORG. This site is hosted and curated by Dr. Vasilis Vasiliou's laboratory at the University of Colorado's Health Sciences Center. ALDH.ORG is dedicated to providing a detailed resource for the aldehyde dehydrogenase gene superfamily.

Genus species (Common Name) Superfamily Records Record Status
Bos taurus (Domestic cow) 4 (In Progress)
Homo sapiens (Human) 19 (Complete)
Mus musculus (House mouse) 20 (Complete)
Rattus norvegicus (Norway rat) 19 (Complete)
 
 

Exon Duplication in Rattus norvegicus ALDH3B2.

(Posted by William Black, 2009-05-31)
The GSRC SAST software identified Rat ALDH3B2 exons 2, 3, 4, 5, and 6 are duplicated ~47000 bases upstream to this gene. This may be due to either a sequencing error in the genomic assembly (NC_005100) or possibly evidence for retroviral involvment in gene duplication. Translation of these five exons yield the bulk of the ALDH peptide domain (Aldeh) according to Pfam analysis. Data are currently being analyzed as to whether or not these exons are transcriptionally supported within cDNA libraries.
 
 
 

ALDH Servers Back Online!

(Posted by William Black, 2009-05-30)
The ALDH servers have been unavailable due to extensive hardware and software upgrades in order to improve their performance.

Currently, we are making ongoing improvements to several of the sequence alignment algorithms as a result from your reportings. Thank you! Keep them coming!

If you happen to find any error reports within the site please feel free to send them to william.black@aldh.org so that they can be rectified. Also, any comments or suggestions to improve the site are welcomed!
 
 
 

The Missing Link Found! Rattus norvegicus ALDH4A1

(Posted by William Black, 2009-01-10)
Well maybe not that missing link ... however, Reference Sequences for Rat ALDH4A1 are missing from the NCBI and EBI databases.

Here we have partly identified exons for ALDH4A1 (Figure 1. highlighted in red) as part of a potential fusion gene in Rat. This may be yet another error in the NCBI and EBI databases and is under investigation. Stay tuned!
Click to Enlarge
Figure 1. Rattus norvegicus ALDH4A1? Highlighted as red exons are orthologous exons between Rat, Mouse and Human.
 
 
 

New Record Feature Added : Alternative Splice Variants

(Posted by William Black, 2008-10-15)
Our laboratory continues to compile data for the aldehyde dehydrogenase (ALDH) gene superfamily to provide a cohesive informational resource regarding this enzyme family.

One area of interest has been defining the alternative splice variants for each ALDH within the superfamily. Alternative splicing is the RNA splicing variation mechanism in which the exons of the primary gene transcript (pre-mRNA) are spliced to produce alternative RNA arrangements yielding a variety of altered peptide products for the same gene. The functional roles for these arrangements remain to be determined and are under current investigation in a number of laboratories.

Prior to our compilations, alternative splice variants in the ALDH superfamily like most other genes remained very much in the gray area. Basic questions such as,
How many alternative splice variants are there for my gene product? or
How many exons are in my transcript? or
Which part of the sequence belongs to which exon?,
can become a matter of dispute depending on which database you visit and occasionally the time of day you visit that particular site.

The National Center for Biotechnology Information (NCBI) webserver AceView, provides one of the better screenings for alternative splice variants for a given gene but not without its share of weaknesses. Screening numerous cDNA sequences for a given gene, AceView breaks down the possible splice variants and gives each variant its own accession identification number (yet another accession identification number to chalk up on a yellow Post-It). However, we caution that you check and recheck the splice variants for your gene as they may often not be a variant at all.

As an example of this we left human ALDH1A3 variant 3 (ALDH1A3_v3) in our database to demonstrate graphically that just because it is reported in AceView, GenBank, RefSeq, Ensembl TransView etc. as an alternative splice variant does not necessarily mean it is actually an alternative splice variant for your gene.

This kind of thing is ubiquitous throughout the major sequence databases and is just one of many. Another example is ALDH8A1_v3.

Our goal is to catalog the existing accession identification numbers available from the major databases to the corresponding alternative splice variant based upon that accession's reported sequence using our proprietary alignment software.

These sequences are continually aligned to the latest genomic sequence assemblies released by NCBI for a given species (i.e. the current assembly for Homo sapiens is NCBI Build 36.3, March 26, 2008 reference assembly). A catalog of alternative splice variants as well as a number of features are produced in both a graphical and tabular format available to the end-users for personal use or reproduction and include,
  • positional coordinates of transcript features (5'untranslated region, coding sequence, 3' untranslated region, polyA signal, polyA tail, etc.)
  • positional coordinates of exons on the transcripts,
  • positional coordinates of triplet codons and peptide translation of these transcripts,
  • positional coordinates of exons on the genomic sequence,
  • positional coordinates of introns on the genomic sequence as well as sequences for the introns
  • information regarding differences in the sequences between the transcripts and the genomic sequence assembly (insertions, deletions and single nucleotide polymorphisms).


We developed this system for several reasons.

We want to ensure that users have the latest available data based upon the latest sequence assemblies released to the community. This isn't always the case when sifting thru other databases.

For example a number of GenBank accessions provide sequence coordinates for coding sequences, UTR's and exon positions according to SPLIGN or some other alignment software on a very dated genomic sequence assembly. However, more recent assemblies do not necessarily reflect those coordinates and may be misleading. We have also noted software errors in EBI's Ensembl curation engine that on occasion does not appropriately translate the transcript sequence or may report a 2-base deletion in the transcript sequence as an actual intron thereby inaccurately recording the number of exons and potentially the number of alternative splice variants for a given gene.

Therefore it is the goal of our curation system to provide users a degree of confidence with the details provided for the latest transcript and genome assemblies and the coordinates derived in a simplified graphical and tabular user interface.

To view this information, select a Gene Record from the 'ALDH Gene Superfamily' menu and click on 'Click Here for Graphical and Tabular Details' found under the Molecular Features Section.

We hope you find this useful and we welcome all input to help make this system a friendlier and useful tool for all. Let us know what you think!

Click to Enlarge
Figure 1. Graphical representation of aligned alternative splice variants now available for Aldehyde Dehydrogenases. Easily distinguish the similarities and differences of ALDH splice variants for a given gene.
 
Click to Enlarge
Figure 2. Detailed graphical representation for each accession ID that has been determined to have valid exon and intron structural integrity. SNPs, Insertions or Deletions found within these sequences are reported and easily viewable for the sequence.
 
Click to Enlarge
Figure 3. Primary peptide sequences are available and sequence anomalies are visually presented.
 
Click to Enlarge
Figure 4. A detailed report of alternative splice variants with hotlinks to source information and details regarding the accession number.
 
Click to Enlarge
Figure 5. Tabular report for each accession ID with sequence information and positional coordinates for the transcript sequence and corresponding genomic sequence.
 
 
 

Aldehyde Dehydrogenase Enzyme Kinetics for Substrates and Inhibitors Section Incorporated

(Posted by William Black, 2007-10-23)
We have added the Enzyme Kinetics for Substrates and Inhibitors section under each ALDH Gene record. This is a compilation of data derived from the literature available from Pubmed and under certain circumstances some data from unpublished studies. We are in a constant state of adding data to this section and would be greatly appreciative for any manuscripts our users recommend for incorpation into the website.
Click to Enlarge
Figure 1.
 
 
 

ALDH Molecular Features Section Revised

(Posted by William Black, 2007-09-30)
The Molecular Features section for each ALDH was revised to reflect proper references for data presented. Each entry is detailed with the Accession Numbers or links to where the data are derived. Also, a number of accession numbers from the various databases were updated and/or retired due to the latest builds from NCBI / EBI, accordingly.
 
 
 

Aldehyde Dehydrogenase, Alcohol Use, and Flushing / Hives

(Posted by William Black, 2007-07-06)
Over the years we have received an enormous number of e-mails regarding questions about facial flushing that may occur following consumption of an alcoholic beverage. As so often is the case, their doctor fails to provide a detailed reason for such an incidence but may mention aldehyde dehydrogenase which leads them to us!

To be frank, we were not exactly prepared for these kind of questions as we were more focused on the molecular biology and chemistry of this gene superfamily. However the web is a wonderful tool that brings users with a vast range of scientific backgrounds together. As a result, I am preparing a Section within the ALDH Overview detailing the role of aldehyde dehydrogenases in the flushing syndrome experienced by so many.
Click to Enlarge
Figure 1.
 
 
 

ALDH.ORG Version 3 Released!

(Posted by William Black, 2007-07-05)
The site is being significantly revised in hopes of providing users with an easier access system to data sought.

At this time, we are releasing the human, mouse and rat ALDH records as a beta test to work out the growing pains as well as obtain valuable feedback from users. Several sections for each ALDH will not be immediately available (polymorphisms, alternative splicing, and substrates specificities) but will be released in the coming weeks.

Please feel free to contact us if you have any questions or comments with the site.
Click to Enlarge
Figure 1.
 
 
 

ALDH Database Revision - Murine Aldh1a7 and Aldh1a4

(Posted by William Black, 2007-04-04)
Mus musculus (mouse) Aldh1a7 and Rattus norvegicus (Norway rat) Aldh1a4 pairwise alignments of their gene products demonstrate 92% sequence homology using ClustalW (version 1.83). Under the nomenclature guidelines for aldehyde dehydrogenases, this homology is indicative that these sequences are in fact orthologs. As a result, these two ALDH's were submitted to the major databases for revision, accordingly, and are annotated under Aldh1a7.
Click to Enlarge
Figure 1. Pairwise alignment of Mouse Aldh1a7 (NCBI Entrez Protein: NP_058968) and Rat Aldh1a4 (NCBI Entrez Protein: NP_058968) demonstrates 92% sequence homology using ClustalW (version 1.83).
 
 

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