Disorders: Microdeletion and Duplication Syndromes

Based on Lupski JR, Stankiewicz P: Genomic disorders: the genomic basis of disease, Totowa, NJ, 2006, Humana Press; Cooper GM, Coe BP, Girirajan S, et al: A copy number variation morbidity map of developmental delay. Nat Genet 43:838-846, 2011; and Weischenfeldt J, Symmns O, Spitz F, et al: Phenotypic impact of genomic structural variation: insights from and for human disease. Nat Rev Genet 14:125-138, 2013.

It is this mechanistic association with segmental duplications that distinguishes this subgroup of deletion and duplication syndromes from others whose breakpoints are highly variable and are not associated with any identifiable genomic feature(s), and whose mechanistic basis appears idiopathic (see Table 6-1). Here we focus on syndromes involving chromosome 22 to illustrate underlying genomic features of this class of disorders.

Deletions and Duplications Involving Chromosome 22q11.2


Figure 6-4 Model of rearrangements underlying genomic disorders. Unequal crossing over between misaligned sister chromatids or homologous chromosomes containing highly homologous copies of segmentally duplicated sequences can lead to deletion or duplication products, which differ in the number of copies of genes normally located between the repeats. The copy number of any gene or genes (e.g., A, B, and C) that lie between the copies of the repeat will change as a result of these genome rearrangements. For examples of genomic disorders, segmental duplications, and the size of the deleted or duplicated region, see Table 6-3.

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Disorders: Microdeletion and Duplication Syndromes

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