Down Syndrome Transcriptome GEDDs

Terms

Lamina associated domains(LADs): Areas of the chromosome which interact with the nuclear lamina. Are highly conserved across species and are often repressed.

H3K4me3: Histone 3, Lysine 4, trimethylated. The fourth amino acid on the third histone is a trimethylated lysine.

Supernumerary: Present in excess

RPKM: Reads per kilobase per million per million.

Mouse Strains

Ts65Dn: Mouse model for down syndrome.

Figures

Figure 1: FC is correlated to conserved areas of the chromosome.

Figure 2: More highly expressed genes are more likely to be downregulated in T1DS and vice versa.

Figure 3: GEDDs are retained even in iPSC.

Figure 4: Loss of repression is consistent in syntenic regions across species. B conveys the DS mouse matches DS human, but not non-DS human.

Figure 5": iLAD genes are not different between the T1DS and T2N, but LADs are different.

Figure 6: There is a correlation between replication time and FC, and between H3K4me3 modification and FC.

Take away

Dosage hypothesis is not entirely true. Instead, differential regulation of epigenetic factors, by triplicated genes (HLCS maybe?), is a large driving factor.