Chromosomal microdeletions: dissecting del22q11 syndrome

@article{Lindsay2001ChromosomalMD,
  title={Chromosomal microdeletions: dissecting del22q11 syndrome},
  author={Elizabeth A. Lindsay},
  journal={Nature Reviews Genetics},
  year={2001},
  volume={2},
  pages={858-868}
}
  • E. Lindsay
  • Published 1 November 2001
  • Biology, Medicine
  • Nature Reviews Genetics
Identifying the genes that underlie the pathogenesis of chromosome deletion and duplication syndromes is a challenge because the affected chromosomal segment can contain many genes. The identification of genes that are relevant to these disorders often requires the analysis of individuals that carry rare, small deletions, translocations or single-gene mutations. Research into the chromosome 22 deletion (del22q11) syndrome, which encompasses DiGeorge and velocardiofacial syndrome, has taken a… Expand
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References

SHOWING 1-10 OF 124 REFERENCES
The 22q11 deletion syndromes.
  • P. Scambler
  • Biology, Medicine
  • Human molecular genetics
  • 2000
TLDR
Current efforts are directed at the study of engineered chromosome mouse models which offer the potential to dissect at least some of the developmental pathways disrupted in this intriguing group of malformation syndromes. Expand
Cloning a balanced translocation associated with DiGeorge syndrome and identification of a disrupted candidate gene
TLDR
Disruption of a gene in 22q11.2 by the breakpoint and haploinsufficiency of this locus in deleted DGS patients make it a strong candidate for the major features associated with this disorder. Expand
A common molecular basis for rearrangement disorders on chromosome 22q11.
TLDR
Models are presented to explain how the LCR22s can mediate different homologous recombination events, thereby generating a number of rearrangements that are associated with congenital anomaly disorders. Expand
Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse.
TLDR
It is suggested that heterozygous deletion of this portion of the DGCR is sufficient for sensorimotor gating abnormalities, but not sufficient to produce the common features of DGS/VCFS in the mouse. Expand
Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders?
TLDR
This review examines whether one or multiple genes can be implicated in the pathogenesis of these segmentally aneusomic syndromes, which include Angelman, Alagille, Williams, Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and DiGeorge/velocardiofacial. Expand
Cloning and comparative mapping of the DiGeorge syndrome critical region in the mouse.
TLDR
This work has mapped 19 murine homologues of genes and nine EST groups from the region deleted in DiGeorge syndrome and found them to be linked on mouse chromosome 16, confirming and extending previous analyses and the contig resources toward the generation of targeted deletions in the mouse. Expand
Molecular mechanism for duplication 17p11.2— the homologous recombination reciprocal of the Smith-Magenis microdeletion
TLDR
Molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. Expand
Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease.
TLDR
It is proposed that haploinsufficiency for TUPLE1 is at least partly responsible for DiGeorge syndrome and related abnormalities. Expand
Cloning of a balanced translocation breakpoint in the DiGeorge syndrome critical region and isolation of a novel potential adhesion receptor gene in its vicinity.
TLDR
The construction of a cosmid contig spanning the translocation breakpoint and the isolation of a gene mapping 10 kb telomeric to the breakpoint are reported, which could play a role in neural crest cells migration, a process which has been proposed to be altered in DiGeorge syndrome. Expand
Chromosome engineering in mice
TLDR
It is reported here that defined deficiencies, inversions and duplications extending to 3-4 cM can be constructed in embryonic stem cells by consecutive targeting of loxP recombination substrates to the end points of a genetic interval followed by Cre-induced recombination, which reconstructs a positive selectable marker which facilitates direct selection of clones with a chromosome structure specific to the relative orientation of theloxP sites. Expand
...
1
2
3
4
5
...