A common molecular basis for rearrangement disorders on chromosome 22q11

Lisa Edelmann, Raj K. Pandita, Elizabeth Spiteri, Birgit Funke, Rosalie Goldberg, Nallasivam Palanisamy, R. S K Chaganti, Ellen Magenis, Robert J. Shprintzen, Bernice E. Morrow

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Abstract

The chromosome 22q11 region is susceptible to rearrangements that are associated with congenital anomaly disorders and malignant tumors. Three congenital anomaly disorders, cat-eye syndrome, der(22) syndrome and velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) are associated with tetrasomy, trisomy or monosomy, respectively, for part of chromosome 22q11. VCFS/DGS is the most common syndrome associated with 22q11 rearrangements. In order to determine whether there are particular regions on 22q11 that are prone to rearrangements, the deletion end-points in a large number of VCFS/DGS patients were defined by haplotype analysis. Most VCFS/DGS patients have a similar 3 Mb deletion, some have a nested distal deletion breakpoint resulting in a 1.5 Mb deletion and a few rare patients have unique deletions or translocations. The high prevalence of the disorder in the population and the fact that most cases occur sporadically suggest that sequences at or near the breakpoints confer susceptibility to chromosome rearrangements. To investigate this hypothesis, we developed hamster-human somatic hybrid cell lines from VCFS/DGS patients with all three classes of deletions and we now show that the breakpoints occur within similar low copy repeats, termed LCR22s. To support this idea further, we identified a family that carries an interstitial duplication of the same 3 Mb region that is deleted in VCFS/DGS patients. We present models to explain how the LCR22s can mediate different homologous recombination events, thereby generating a number of rearrangements that are associated with congenital anomaly disorders. We identified five additional copies of the LCR22 on 22q11 that may mediate other rearrangements leading to disease.

Original languageEnglish (US)
Pages (from-to)1157-1167
Number of pages11
JournalHuman Molecular Genetics
Volume8
Issue number7
DOIs
StatePublished - 1999

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Chromosome Disorders
DiGeorge Syndrome
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Chromosomes
Tetrasomy
Genomic Segmental Duplications
Monosomy
Homologous Recombination
Trisomy
Cricetinae
Haplotypes

ASJC Scopus subject areas

  • Genetics

Cite this

Edelmann, L., Pandita, R. K., Spiteri, E., Funke, B., Goldberg, R., Palanisamy, N., ... Morrow, B. E. (1999). A common molecular basis for rearrangement disorders on chromosome 22q11. Human Molecular Genetics, 8(7), 1157-1167. https://doi.org/10.1093/hmg/8.7.1157

A common molecular basis for rearrangement disorders on chromosome 22q11. / Edelmann, Lisa; Pandita, Raj K.; Spiteri, Elizabeth; Funke, Birgit; Goldberg, Rosalie; Palanisamy, Nallasivam; Chaganti, R. S K; Magenis, Ellen; Shprintzen, Robert J.; Morrow, Bernice E.

In: Human Molecular Genetics, Vol. 8, No. 7, 1999, p. 1157-1167.

Research output: Contribution to journalArticle

Edelmann, L, Pandita, RK, Spiteri, E, Funke, B, Goldberg, R, Palanisamy, N, Chaganti, RSK, Magenis, E, Shprintzen, RJ & Morrow, BE 1999, 'A common molecular basis for rearrangement disorders on chromosome 22q11', Human Molecular Genetics, vol. 8, no. 7, pp. 1157-1167. https://doi.org/10.1093/hmg/8.7.1157
Edelmann L, Pandita RK, Spiteri E, Funke B, Goldberg R, Palanisamy N et al. A common molecular basis for rearrangement disorders on chromosome 22q11. Human Molecular Genetics. 1999;8(7):1157-1167. https://doi.org/10.1093/hmg/8.7.1157
Edelmann, Lisa ; Pandita, Raj K. ; Spiteri, Elizabeth ; Funke, Birgit ; Goldberg, Rosalie ; Palanisamy, Nallasivam ; Chaganti, R. S K ; Magenis, Ellen ; Shprintzen, Robert J. ; Morrow, Bernice E. / A common molecular basis for rearrangement disorders on chromosome 22q11. In: Human Molecular Genetics. 1999 ; Vol. 8, No. 7. pp. 1157-1167.
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AU - Palanisamy, Nallasivam

AU - Chaganti, R. S K

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