Dear Anders, Thanks for doing this analysis. Can you tell us what your definition of a haplotype was in this situation? Was it a specific number of matching consecutive SNPs? My personal opinion is that reason #1 is the primary reason why relatively few autosomal haplotypes were seen in your analysis. I think that this situation again brings up a topic that we discussed on the ISOGG list in February: DNA recombination hotspots. Slide 29 in the presentation at www.stats.ox.ac.uk/~mcvean/DTC/BIOINF/Lectures/Recombination.ppt indicates that there are about 33,000 recombination hotspots found in the Phase II HapMap project. Slide 31 explains that the hotspot motif CCTCCCTNNCCAC accounts for 40% of all human hotspots. There is also a good review article on this topic in Nature Reviews Genetics, March 2010, p. 221-233. It would be helpful to have a complete list of these blocks and their associated boundaries. Eventually it makes sense for us to start looking at phased haplotypes for each block that is bounded by a hotspot and then try to associate each haplotype with a specific ancestor or series of ancestors. Some of these haplotype blocks have ancient origins going back to Neanderthal or Denisovan ancestors. Such blocks would contain about 30 SNPs on average using 23andMe version 3 data. Sincerely, Tim Janzen -----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of Anders Pålsen Sent: Friday, November 18, 2011 2:39 AM To: [email protected] Subject: [AUTOSOMAL-DNA] Autosomal Haplotype Clustering Patterns - Actual or Error? List, I have found this pattern of haplotype clustering within individuals from Norway, Sweden and Finland on Chr 1 using 38.5k SNP: This raises the questions why its like this. I suspect its the following reasons: 1. The effect of recombination splitting or killing haplotypes. However the maximum haplotype size in clusters is 500kb questions recombination as the effect. 2. The effect of limited population data. Its possible more individuals and populations would reduce the number of unique haplotype clusters. 3. The effect of undetected errors in the genotypes. However no correlation between high unique haplotypes found in individuals and high detected genotype error rate for these. 4. The effect of incorrect phasing as the result of errors in genotype or/and ordinary phasing error as result of the model used. 5. The effect of haplotype or mutation extinction. Recent individual haplotypes or mutations have limited spread generally, while older haplotype clusters or mutations have larger geographic spread. Do anyone else have more suggestions to explain this? Anders

Thanks for your reply Tim. I have to make a correction about #1. Its not 500kb but maximum 500 consecutive SNP. I also tried some more parameters after this posting at #1. I reduced it first to maximum 100 SNP but it only reduced to 1324 unique haplotype clusters from the initial 1344. Reducing it further to max 10 SNP only reduced to 1189 unique haplotype clusters. Reducing it even more to 5 SNP reduced only to 962 unique haplotype clusters. First if reducing it to 2 SNP it dropped much down getting only 277 unique haplotype clusters remained. Using maximum 1 SNP crashed the software. It make sense that allowing for larger haplotypes generate more unique haplotypes than allowing only for smaller haplotypes. So what I infer from this is that these unique haplotype clusters is rather small and not very large. These numbers have been generated from software made for finding genetic diseases from haplotypes where you mark individuals with certain traits cases and check them vs the controls. If there is any haplotype strongly associated with a trait the associated haplotype is found. These haplotypes are usually not very large. Just check the SNP used by 23andme health section.. So is also the cases with these haplotypes. The software do for many haplotypes infer parent-child relationships between them indicating that haplotype mutations are in the picture at least when I check at the individual level. Anders ________________________________ Fra: Tim Janzen <[email protected]> Dear Anders,     Thanks for doing this analysis.  Can you tell us what your definition of a haplotype was in this situation?  Was it a specific number of matching consecutive SNPs?  My personal opinion is that reason #1 is the primary reason why relatively few autosomal haplotypes were seen in your analysis. ... Tim Janzen