Wednesday, November 22, 2006

"Down Syndrome Critical Region" isn't?

Gnome writes "Down syndrome (DS) results from the most common viable human chromosomal abnormality, occurring in 1 out of 700 live births. In addition to an entire extra chromosome 21 (free trisomy), DS is also caused by translocated or duplicated portions of chromosome 21. In 1987, the "Down Syndrome Critical Region" (DSCR) was mapped to the short arm of chromosome 21 using quantitative Southern blots of genomes of DS patients and rare patients with ostensibly normal karyotypes. The DSCR was later refined as a 5.4 megabase region around 21q22.3. Known genes in the DSCR are highly conserved between humans and mice (on chromosome 16). Chimeric mice containing a human chromosome 21 exhibit learning deficits and cardiac defects reminiscent of Down syndrome. Even the fruit fly homolog of the DSCR regulates learning. Now, investigators generated transgenic mice with precise DSCR trisomy or monosomy by clever use of asymmetric Cre-Lox sites. They report that mice with three copies of the DSCR do not show the same facial skeletal abnormalities found in mice with larger duplicated regions. Surprisingly, trisomic DSCR mice are larger and monosomic DSCR are smaller than normal, though mice trisomic through a ~3-fold larger, overlapping region are smaller than normal. The authors state that these results refute the predictions of the nearly 3 decade old hypothesis that DS is caused by dose effects of genes within the DSCR."
PubMed Olson et al. Science 2004 Oct 22;306(5696):687-90
A Chromosome 21 Critical Region Does Not Cause Specific Down Syndrome Phenotype

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