Reviewer's report 
 Tracing Ancestry With Methylation Patterns:Most Crypts Appear Distantly Related in Normal Title: 
Adult Human Colon 
 1  7 November 2003 Version: Date: 
 Nick Wright Reviewer: 
Reviewer's report: 
1. Examining the figure 3 there remain very few observations-few crypt pairs and only the same few 
branched crypts. I have commented upon the importance of the three-dimensional lattice in the context of inter-crypt relationships in my previous review. The conclusions are far-reaching to be based on such a small number of observations, as I previously remark. 
2. A major point is that there are no positive controls; attached crypts were examined in the colon of 
a patient with quiescent ulcerative colitis. In disease states, the number of crypts apparently in fission can rise rapidly to very high levels ~ 30-40 %. It is generally considered that this is indeed a 
regenerative phenomenon and therefore indeed due to fission. One would then think, a priori, that 
such apparently dividing crypts should be closely related as the fission event would have definitely occurred within the last hours or days. If the methodology is appropriate, then one might expect that these crypts would be closely-related and this would allay fears that the method is not capable of 
picking up closely-related crypts. 
If this could be done, then this would give added verisimilitude to the proposal that crypts apparently 
fission in normal or quiescent mucosa are either (a) taking a very long time to divide or (b) in the 
process of fusion. 
This is an interesting paper, which raises interesting proposals and conclusions. It would be much 
more valuable if the above points, and especially point 2 could be considered. 
Reviewer's report 
 Tracing Ancestry With Methylation Patterns:Most Crypts Appear Distantly Related in Normal Title: 
Adult Human Colon 
 1  7 November 2003 Version: Date: 
 Nick Wright Reviewer: 
Reviewer's report: 
1. Examining the figure 3 there remain very few observations-few crypt pairs and only the same few 
branched crypts. I have commented upon the importance of the three-dimensional lattice in the context of inter-crypt relationships in my previous review. The conclusions are far-reaching to be based on such a small number of observations, as I previously remark. 
2. A major point is that there are no positive controls; attached crypts were examined in the colon of 
a patient with quiescent ulcerative colitis. In disease states, the number of crypts apparently in fission can rise rapidly to very high levels ~ 30-40 %. It is generally considered that this is indeed a 
regenerative phenomenon and therefore indeed due to fission. One would then think, a priori, that 
such apparently dividing crypts should be closely related as the fission event would have definitely occurred within the last hours or days. If the methodology is appropriate, then one might expect that these crypts would be closely-related and this would allay fears that the method is not capable of 
picking up closely-related crypts. 
If this could be done, then this would give added verisimilitude to the proposal that crypts apparently 
fission in normal or quiescent mucosa are either (a) taking a very long time to divide or (b) in the 
process of fusion. 
This is an interesting paper, which raises interesting proposals and conclusions. It would be much 
more valuable if the above points, and especially point 2 could be considered. 
Please review this paper.
user
Reviewer's report 
 Tracing Ancestry With Methylation Patterns:Most Crypts Appear Distantly Related in Normal Title: 
Adult Human Colon 
 1  7 November 2003 Version: Date: 
 Nick Wright Reviewer: 
Reviewer's report: 
1. Examining the figure 3 there remain very few observations-few crypt pairs and only the same few 
branched crypts. I have commented upon the importance of the three-dimensional lattice in the context of inter-crypt relationships in my previous review. The conclusions are far-reaching to be based on such a small number of observations, as I previously remark. 
2. A major point is that there are no positive controls; attached crypts were examined in the colon of 
a patient with quiescent ulcerative colitis. In disease states, the number of crypts apparently in fission can rise rapidly to very high levels ~ 30-40 %. It is generally considered that this is indeed a 
regenerative phenomenon and therefore indeed due to fission. One would then think, a priori, that 
such apparently dividing crypts should be closely related as the fission event would have definitely occurred within the last hours or days. If the methodology is appropriate, then one might expect that these crypts would be closely-related and this would allay fears that the method is not capable of 
picking up closely-related crypts. 
If this could be done, then this would give added verisimilitude to the proposal that crypts apparently 
fission in normal or quiescent mucosa are either (a) taking a very long time to divide or (b) in the 
process of fusion. 
This is an interesting paper, which raises interesting proposals and conclusions. It would be much 
more valuable if the above points, and especially point 2 could be considered. 
assistant