title: Mapping of balanced chromosome translocation breakpoints to the basepair level from microdissected chromosomes.
abstract: The analysis of structural variants associated with specific phenotypic features is promising for the elucidation of the function of involved genes. There is, however, at present no approach allowing the rapid mapping of chromosomal translocation breakpoints to the basepair level from a single chromosome. Here we demonstrate that we have advanced both the microdissection and the subsequent unbiased amplification to an extent that breakpoint mapping to the basepair level has become possible. As a case in point we analysed the two breakpoints of a t(7;13) translocation observed in a patient with split hand/foot malformation (SHFM1). The amplification products of the der(7) and of the der(13) were hybridized to custom-made arrays, enabling us to define primers at flanking breakpoint regions and thus to fine-map the breakpoints to the basepair level. Consequently, our results will also contribute to a further delineation of causative mechanisms underlying SHFM1 which are currently unknown.
authors.affiliation: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Obenauf
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarzbraun
authors.forename: Martina
authors.initials: M
authors.lastname: Auer
authors.forename: Eva M
authors.initials: EM
authors.lastname: Hoffmann
authors.forename: Julie
authors.initials: J
authors.lastname: Waldispuehl-Geigl
authors.forename: Peter
authors.initials: P
authors.lastname: Ulz
authors.forename: Barbara
authors.initials: B
authors.lastname: Günther
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Duba
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Geigl
mesh_terms: D001483:Base Sequence; D002871:Chromosome Banding; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping / Q000379:methods*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005532:Foot Deformities, Congenital / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007834:Lasers; D008297:Male; D042282:Microdissection / Q000379:methods; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C100596:DLX5 protein, human; C491014:DLX6 protein, human; D018398:Homeodomain Proteins; C484606:SEM1 protein, human; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex