Animal models for human contiguous gene syndromes and other genomic disorders
Genet. mol. biol
;
27(3): 305-320, Sept. 2004. ilus, tab
Article
in English
| LILACS
| ID: lil-366172
RESUMO
Genomic disorders refer to a group of syndromes caused by DNA rearrangements, such as deletions and duplications, which result in an alteration of normal gene dosage. The chromosomal rearrangements are usually relatively small and often difficult to detect cytogenetically. In a subset of such conditions the rearrangements comprise multiple unrelated contiguous genes that are physically linked and thus have been referred to as contiguous gene syndromes (CGS). In general, each syndrome presents a complex clinical phenotype that has been attributed generally to dosage sensitive gene(s) present in the responsible chromosomal interval. A common mechanism for CGS resulting from interstitial deletion/duplication has recently been elucidated. The DNA rearrangements result from nonallelic homologous recombination (NAHR) utilizing flanking low-copy repeats (LCRs) as recombination substrates. The resulting rearrangements often involve the same genomic region, a common deletion or duplication, making it difficult to assign a specific phenotype or endophenotype to a single responsible gene. The human and mouse genome sequencing projects, in conjunction with the ability to engineer mouse chromosome rearrangements, have enabled the production of mouse models for CGS and genomic disorders. In this review we present an overview of different techniques utilized to generate mouse models for selected genomic disorders. These models foment novel insights into the specific genes that convey the phenotype by dosage and/or position effects and provide opportunities to explore therapeutic options.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
DNA
/
Chromosome Disorders
/
Disease Models, Animal
Limits:
Animals
/
Humans
Language:
English
Journal:
Genet. mol. biol
Journal subject:
Genetics
Year:
2004
Type:
Article
/
Project document
Affiliation country:
United States
Institution/Affiliation country:
Baylor College of Medicine/US
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