Trinucleotide repeats triggers for genomic disorders 英文参考文献.docVIP

Kozlowski et al. Genome Medicine 2010,2:29 /content/2/4/29 MINIRE VIE W Trinucleotide repeats: triggers for genomic disorders? Piotr Kozlowski , Krzysztof Sobczak and Wlodzimierz J Krzyzosiak* ? ? transcription splicing and translation [3]. ese TNRs Abstract include repeats of CGG, CAG and AGG, which are overrepresented in human exons [4]. On the other hand, AAT, AAC and AAG are probably disadvantageous as they are negatively selected in exons [4]. TNR sequences undergo mutations at a very high frequency [5], and this may increase disease risk or trigger disease in speci?c conditions [6,7]. Among the various sequence repeats that shape the human genome, trinucleotide repeats have attracted special interest as a result of their involvement in a class of human genetic disorders known as triplet repeat expansion diseases. Recently, long TGG repeat tracts were shown to be implicated in a genomic disorder resulting from chromosome 14q32.2 deletion. Various dierent mechanisms might trigger this deletion, and looking at the problem from a structural biology perspective may help. Deeper insight into repeated sequences and their features may shed light on the mechanisms involved in this microdeletion and similar genomic rearrangements. Over the past two decades our thinking about the links between STRs and human diseases has been dominated by neurological disorders known as trinucleotide repeat expansion diseases (TREDs) [8,9]. ere are over 20 diseases that belong to this group, the best known of which are fragile X syndrome (FXS), myotonic dystrophy type 1 (DM1), Huntington’s disease (HD) and spino- cerebellar ataxias (SCAs). FXS is caused by an expanded CGG repeat located in the 5’ untranslated region (UTR) of the fragile X mental retardation 1 gene (FMR1); DM1 is triggered by an expanded CUG repeat located in the 3’ Genomic repeats and hu