Allele specific timing profiles.

<p>A: Principle of the TimEX methods: DNA content from cells in the G1 and S phases of the cell cycle is compared. Cells in G1 contain 2 copies of each genomic region. By contrast, cells in S contain between 2 and 4 copies of each genomic regions and the number of copies in S is inversely proportional to replication timing. The S/G1 ratio can therefore be used as a surrogate for replication timing. B: Histograms representing the DNA content profiles of exponentially growing cultured basophilic erythroblasts (presort), of the same cells after sorting the S phase fraction (post sort) and of circulating white blood cells that are almost exclusively in the G1 phase of the cell cycle. Cells were labeled with Propidium iodide for 15 minutes. C: Pedigree of family FNY01. D. Plots illustrating the replication timing of the maternal and paternal homologs in a 10 Mb region on chr16 for FNY01 3_2 and 3_3. The data was generated by binning the read depth of heterozygous SNPs in 500 bp windows, applying a Gaussian smoothing filter (sigma = 100 kp) and calculating the S/G1 ratio for the maternal and the paternal homologs. The profiles are discontinuous because some reion of the genome did not contains any heterozygous SNPs. Replication of the homologs is tightly regulated. The location of Refseq genes is indicated below the timing profiles to give a sense of scale. E: Scatter-plots of the S/G1 ratios of the allele-depth of heterozygous SNPs in 5 kb windows for the maternal and paternal homologs. Coefficient of correlation between the two homolog is very high (r² = 0.95). F: Histogram of the distribution of the difference between the S/G1 ratio of the maternal and paternal homologs. The two homologs replicate within 48 minutes of each other in about 88% of the genome. The black bars represent the asynchronous regions.