A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome - PubMed (original) (raw)

The WBS region at 7q11.23. The rearrangement breakpoints in translocation patient 11719 and inversion patient 15441, as determined by FISH, are shown (top). We determined the locations of _Not_I sites for PFGE on the basis of both DNA sequence analysis and published work. The four probes used for interphase FISH are represented in color as they appear in Fig. 2. The 18 probes used to fine-map the inversion breakpoints and to test for subtle chromosome rearrangements are indicated by gray circles. (left to right: RP11-421B22, RP5-845I21, RP4-635O5, HSC7E610, CTB-23I15, CTA-208H19, CTA-315H11, cos16g10, cos82c2, cos34b3, RP11-122H9, cos209c11, RP11-267N24, RP11-54H15, CTB-139P11, CTA-356E1, CTB-122E10, HSC7E139). Genes are depicted as arrows where the transcriptional orientation (5′ to 3′) is known, and as blocks when it is not known. An additional seven genes mapping between WBSCR14 and ELN were recently reported at the 2001 International Congress of Human Genetics (L.F. Magano et al.). DNA sequence scaffolds from Celera (component 3 assembly) and the public genome project are shown. Repetitive gene sequences within the duplicons are color-coded as in the legend; the duplicons themselves are presented as large vertical boxes shaded blue. The duplicons consist of actively transcribed genes (FKBP6, GTF2I, GTF2IRD2 and NCF1), highly conserved pseudogenes with near-identical genomic structure (GTF2IP1, GTF2IP2, NCF1P1, NCF1P2, GTF2IRD2P1, FKBP6P1, FKBP6P2) and pseudogenes corresponding to ancestral progenitors found at other sites on chromosome 7 (_PMS2_-like genes, three STAG3 pseudogenes and POM pseudogenes)–,. Blocks of direct and inverted repeats exist between the duplicons. These are represented as A, B and C according to established nomenclature. They include directly repeated blocks of DNA sequences greater than 65 kb in length with 98% identity within clones CTA-269P13 and CTA-350L10, and larger, inverted blocks spanning more than 120 kb, also with 98% identity within clones RP11-313P13 and RP5-953A4. We also identified a 1-kb sequence with 85% similarity to the pMD24 telomere-associated sequence in each WBS duplicon (in the same orientation as GTF2I/GTF2IP1). All probes are available upon request; additional information can be found at

http://www.genet.sickkids.on.ca/chromosome7/

. The minimal regions to which the inversion breakpoints could be localized, based on our analysis, are depicted by horizontal boxes at the bottom of the figure.