title: Natural variation of gene models in Drosophila melanogaster.
abstract: BACKGROUND
  Variation within splicing regulatory sequences often leads to differences in gene models among individuals within a species. Two alleles of the same gene may express transcripts with different exon/intron structures and consequently produce functionally different proteins. Matching genomic and transcriptomic data allows us to identify putative regulatory variants associated with changes in splicing patterns.
  
  
  RESULTS
  Here we analyzed natural variation of splicing patterns in the transcriptomes of 81 natural strains of Drosophila melanogaster with known genotypes. We identified dozens of genotype-specific splicing patterns associated with putative cis-splicing quantitative trait loci (sQTL). The majority of changes can be explained by mutations in splice sites. Allelic-imbalance in splicing patterns confirmed that the majority are regulated mainly by cis-genetic effects. Remarkably, allele-specific splicing changes often lead to qualitative changes in gene models, yielding many isoforms not previously annotated. The observed alterations are typically outside protein-coding regions or affect only very short protein segments.
  
  
  CONCLUSIONS
  Overall, the sets of gene models appear to be flexible within D. melanogaster populations. The observed variation in splicing patterns are predicted to have limited effects on the encoded protein sequences. To our knowledge, this is the first sQTL mapping study in Drosophila.
authors.affiliation: University of Southern California, Los Angeles, CA, USA. kurmanga@usc.edu.|Institute for Information Transmission Problems (Kharkevich Institute), Moscow, Russia. kurmanga@usc.edu.
authors.forename: Yerbol Z
authors.initials: YZ
authors.lastname: Kurmangaliyev
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA. favorov@sensi.org.|Vavilov Institute of General Genetics, Moscow, Russia. favorov@sensi.org.|Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russia. favorov@sensi.org.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Favorov
authors.affiliation: University of Southern California, Los Angeles, CA, USA. osman.noha@yahoo.com.|National Research Center, Dokki, Giza, Egypt. osman.noha@yahoo.com.
authors.forename: Noha M
authors.initials: NM
authors.lastname: Osman
authors.affiliation: Memorial Sloan Kettering Cancer Center, Zuckerman Research Center, New York, NY, USA. lehmann@cbio.mskcc.org.
authors.forename: Kjong-Van
authors.initials: KV
authors.lastname: Lehmann
authors.affiliation: University of Southern California, Los Angeles, CA, USA. dcampo@usc.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Campo
authors.affiliation: University of Southern California, Los Angeles, CA, USA. msalomon@usc.edu.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Salomon
authors.affiliation: University of Southern California, Los Angeles, CA, USA. jtower@usc.edu.
authors.forename: John
authors.initials: J
authors.lastname: Tower
authors.affiliation: Institute for Information Transmission Problems (Kharkevich Institute), Moscow, Russia. gelfand@iitp.ru.|Lomonosov Moscow State University, Moscow, Russia. gelfand@iitp.ru.
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Gelfand
authors.affiliation: University of Southern California, Los Angeles, CA, USA. snuzhdin@usc.edu.|Saint Petersburg Polytechnical University, St Petersburg, Russia. snuzhdin@usc.edu.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Nuzhdin
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D017398:Alternative Splicing; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D005091:Exons; D020869:Gene Expression Profiling; D014644:Genetic Variation; D005838:Genotype; D008957:Models, Genetic; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D022821:RNA Splice Sites; D059467:Transcriptome
chemical_list: D022821:RNA Splice Sites