and washed with abundant water. Once they were dried, images were re- corded using a camera (DP70; Olympus) on a research microscope (Provis AX70; Olympus) with photomicrography controller (Olympus). They were captured with immersion oil at room temperature using DP Controller and DP Manager softwares (Olympus) with a Plan-Apochromat 100× 1.40 oil objective to get a 1,000 magnification. Metaphases were analyzed for har- lequin staining. Each color switch was scored as one SCE. Statistical analysis and p:q ratio determination Fisher’s exact test (two sided) was used to calculate statistical significance of proportions of short telomeres in G3 littermates, T-SCE, SFEs, MTSs, chromosome fusions, fragments, breaks, and aneuploidy. The Wilcoxon- Mann-Whitney rank sum test was used for statistical comparison of median telomere length in MEFs. Statistical comparison of survival data was performed using the log rank (Mantel-Cox test). p:q telomere ratios were calculated using telomere length values from TFL-Telo for p and q arms of individual chromosomes. Ratios were calculated by dividing q/p, and proportions of chromosomes with p:q ratios greater than fivefold (q/p ≥ 5 or ≤ 0.2) were calculated. Chromosome arms with SFEs were deemed to have p:q ratios ≥5 (Morrish and Greider, 2009). A two-sided Student’s t test was used to calculate the statistical significance of p:q ratios and SCE. Unless otherwise indicated in the figure legend, all data with error bars represent mean ± SEM. Online supplemental material Fig. S1 shows that cells derived from human Seckel patients show increased telomere fragility. Fig. S2 shows that telomerase deficiency does not worsen cranial phenotypes of Seckel mice. Online supplemental material is avail- able at http://www.jcb.org/cgi/content/full/jcb.200908136/DC1. We thank R. Serrano, E. 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