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Microdeletion Microduplication 谢伟伟 5/9/2012 Background Definition of microdeletion and microduplication  The loss (or gain )of a tiny piece of a chromosome, a piece so small its absence(or presence ) is not apparent on ordinary examination (using a regular light microscope to look at chromosomes prepared in the usual fashion).  A few common and well-known disease-causing rearrangements in this size-range example  3q29 microdeletion syndrome  3q29 microduplication syndrome  If you magnify chromosomes about 1000 times and look at them down a microscope, a small piece may be visibly missing from the end of the long arm of chromosome 3. Syndromes in DECIPHER: 58  https://decipher.sanger.ac.uk/syndromes  Overview  Aberrations  Phenotypes  Citations  Karyotype Syndromes  Microdeletion : cri du chat syndrome , Angelman, DiGeorge, Prader-Willi, and Williams syndromes...  Microduplication :Charcot-Marie-Tooth disease type 1A (CMT1A) and the microduplication 22q11.2 syndrome… Karyotype in 58 Del= Dup= reason  Copy-Number Variation  Genomic Architecture and Molecular Mechanisms of Formation 1. Low-Copy Repeats(LCRs) 2. Nonallelic Homologous Recombination 3. Nonhomologous End Joining(NHEJ) 4. Microhomology-Mediated Replication Error Mechanisms reason  Position effect  Dosage effect  Background genetype  Lyon hypothesis  Psendodicentric （假双着