Animal models for human contiguous gene syndromes and other genomic disorders

Katherina Walz, Patricia Fonseca, James R. Lupski

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


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 enclophenotype 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. Copyright by The Brazilian Society Genetics.

Original languageEnglish (US)
Pages (from-to)305-320
Number of pages16
JournalGenetics and Molecular Biology
Issue number3
StatePublished - 2004
Externally publishedYes


  • Contiguous gene syndromes
  • Genomic disorders
  • Microdeletion
  • Microduplication

ASJC Scopus subject areas

  • Genetics


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