lvandela@bccrc.ca

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Department:	Terry Fox Laboratory (@ the BCCRC since 2000)
Research Role:	Graduate Student/Postdoctoral Fellow Alumnus
Education:	B.A.Sc. (Engineering Physics), University of B.C., 1996
Birthplace:	Chilliwack, British Columbia, Canada
Phone:	604-675-8000 ext.7768

Research Interests:

My work has focused on the biological function of repetitive DNA. Transposable elements (TEs), in particular, are ubiquitous among eukaryotes, and their dysregulation has been shown to result in a broad spectrum of pathologies. TEs recognizable by current methods comprise more than 40 percent of human DNA. Elements transcribed by RNA polymerase II (pol II) are of special interest because of the enhancers, promoters, and splicing and polyadenylation signals they harbour, some of which have been shown to impact the regulation of nearby genes. Most mammalian TEs are known as retroelements because they arise as a result of RNA being reverse transcribed and reinserted elsewhere in the host genome.

Investigations of TE polymorphisms among primates have led to interest in other repeats, including those involved in DNA double-strand break repair

Thesis work

• Retroelement distributions in the human genome: We conducted a global analysis of the genomic densities of various families of TEs with respect to local nucleotide sequence composition and gene position. This work suggested that many endogenous retroviruses have negative impacts even some distance upstream and downstream of genes
• Analysis of TEs in the human and mouse transcriptomes: We conducted a global analysis of prevalence of TEs in mRNAs of known human and mouse genes by looking at the sequence they contribute to the untranslated regions of human mRNAs. We found that genes more likely permissive for TE sequence are also more often specialized in their function. Conversely, genes involved in very basic cellular life processes are significantly less likely to contain TEs in their transcripts.
• Analysis of genic distributions of retroviral-like repeat families in humans: To investigate further the phenomenon of TE orientation bias in genic regions, we analyzed genic distributions of endogenous retroviral-like (ERV) elements. We found significant variation in genic populations between families of ERVs. However, genic ERVs in the same orientation as the gene, regardless of family, showed a dramatic density reduction just inside the 5' borders of genes which persisted all across transcribed regions. This may be a reflection of the propensity of ERVs to cause premature polyadenylation or splicing. Further studies are warranted.
• Analysis of repeats and genomic stability: We analyzed retroelement stability after insertion by comparing loci of apparent retroelement insertion in the human and chimpanzee genomes with the orthologous loci in Rhesus monkey. Thirty-seven cases of precise retroelement deletion were found, and some of these were confirmed by PCR in a panel of primates. The presence of 7-20 bp flanking identical sequences likely mediates these deletions. By comparison, 10-20 fold more deletions occurred entirely internal to Alu elements, involving internal similar sequences.

Funding

Computer resources

Hardware

Most recently, analysis was done on a P4 2.6 GHz machine with 120 GB IDE HD and 1.2 GB RAM. Other analyses were done on machines at collaborator Patrik Medstrand's lab in Sweden.

My software

Machine-learning tools - A Hidden Markov Model aligner and an artificial neural network program for analysis of gene splicing. Both were written in C++.

MultAln - A multiple alignment program written for  Holger Hoos of the UBC CS department. It is written in C and compares performance of multiple sequence alignment methods.

Genomic analysis - A collection of command line Perl scripts that filters, summarizes, and analyzes mappings of repeat and gene data.

Sequence tools interface - Perl CGI scripts that provide interfaces to BLAST (Basic Local Alignment Search Tool) and sequence retrieval scripts.

See Also:

• Dixie L. Mager