2020生物信息学学习领取12国外收集chapter5.pdfVIP

CHAPTER 5 GENERAL SUMMARY 5.1 OVERALL SUMMARY Chromosomal rearrangements, such as deletions, duplications, inversions and translocations, account for a broad spectrum of human g ic disorders, luding Triple-X, Klinefelter, Turner, Down, Edwards, Patau, DiGeorge, Smith-Magenis, Williams, Prader-Willi and Angelman syndrome, to name just a few examples (Iliopoulos 2006; Kesler 2007; Tucker 2007; Mégarbané 2009; Tartaglia 2010; Wikström 2011). In order to unravel dosage-sensitive genomic regions and genes, and to gain better understanding of the development and pathophysiology of these human diseases, chromosomal rearrangements need to be generated in model organisms. The mouse is an excellent organism of choice because it shares many similarities with humans, both in terms of biology and g ics, and because its genome can be easily modified using chromosome engineering techniques, allowing the generation of defined chromosomal rearrangements. To date, many mouse models carrying defined genomic rearrangements have been successfully developed (Corral 1996; Jiang 1998; Sago 1998; Yang 1998; Kimber 1999; Lindsay 1999; Tsai 1999; Zheng 1999; Puech 2000; Lindsay 2001; Merscher 2001; Walz 2003; Walz 2003; Olson 2004; Yan 2004; Bi 2005; Skryabin 2007; Li 2009), giving new insights into dosage-sensitive genes involved in these human g ic disorders, and unravelling the molecular and cellular mechanisms underlying these pathologies. During my PhD I have used chromosome engineering techniques to develop two monosomic mouse models carrying defined chromosomal deletions syntenic with 21q11.2!q21