Sex differences in congenital heart disease in Down syndrome: study data from medical records and questionnaires in a region of Japan.

Reports indicate lower Down syndrome (DS) survival among females than among males in Australia, contrasting with female longevity in the general population. Using data on 1310 people with DS (626 females and 684 males) in Japan from five hospitals' medical records and questionnaires completed by parents of people with DS, we investigated sex differences in congenital heart disease (CHD), which may be related to mortality. The CHD rate was significantly higher for females (354, 57%) than for males (338, 49%; p=0.010). Significantly more females (199, 32%) than males (175, 26%) underwent surgery for CHD (p=0.018).

Integration of exogenous DNA into mouse embryonic stem cell chromosomes shows preference into genes and frequent modification at junctions.

Chromosomal integration of exogenous DNA in mammalian cells allows stable gene expression for a variety of biological applications. Although it is presumably mediated by DNA repair machinery, little is known regarding site preferences and other characteristics. We isolated and analyzed 256 chromosomal-plasmid DNA integration junctions from 158 plasmid integrants after electroporation in mouse embryonic stem (ES) cells. The frequency of integrations in transcription units (40%) showed a slight but significant increase over the frequency estimated by computer simulation of random events (30%), suggesting preferential integration into genes. Microarray analysis revealed preference into genes, which are expressed in mouse ES cells. In contrast, bias toward integrations around transcriptional start sites, CpG islands and repeat elements was not observed. Furthermore, all host chromosome sequences as well as the majority of plasmids (96%) at the integration junctions were modified by deletions and/or insertions of additional nucleotides. Detailed analyses revealed frequent stem loop/hairpin formation mediated by weak homologies near plasmid ends before integration. Our study sheds light on a natural fate of exogenous DNA, which preferentially integrates into transcriptionally active chromosomal sites and by an imprecise end-joining pathway, associated with highly frequent modification of the end sequences.