Medinfo.ufl

1. http://medinfo.ufl.edu/other/ord/exec_comm_oct2007.pptThe Mouse models Core

2. Question: Should we bring a panel of Advanced Recombinant Inbred (ARI) C57BL/6J (B) x DBA/2J (D) Mice to Gainesville?

6. What makes the BXD ARI mice or the CTC RI mice even more powerful is the availability of bioinformatics tools that aloows us to analyze phenotypes in the context of genotypic variations using algorithms, SNP and MS data to map QTLs modulating each measued phenotype ( relative survival, blood pressure, liver enzyme etc -- each is a phenotype .What makes the BXD ARI mice or the CTC RI mice even more powerful is the availability of bioinformatics tools that aloows us to analyze phenotypes in the context of genotypic variations using algorithms, SNP and MS data to map QTLs modulating each measued phenotype ( relative survival, blood pressure, liver enzyme etc -- each is a phenotype .

8. This slide shows how the mice are generated: The B6 are mated to D2 to generate F1 mice, which are all identical. The F1 mice are crossbred to generate the F2 population -- in this process recombinations in chromosomes take place in a random fashion such that each F2 mouse has different combination of the parental chromosomes. Because the genetic diversity of the F2 generation is random -- you cannot reproduce an interesting phenotype if you found it -- it is gone. So, now we randomly pair a male and female from the F2 and assign each pair as the new ancestors of teach of the RI lines. The progeny of the F2 parents are brother-sister bred for 20 generations at which point the chromosome is fixed and homozygosity is achieved for each line. Because the F2 parents were all genetically distinct, each of the derived BXD lines is also genetically distinct from each other, yet members of the same line are identical (inbred). The entire panel is 100 ( 40 regular RI 60 ARI). The ARI mice were derived by Williams et al in Memphis and they are more powerful than the RI mice because they have twice as many recombinations in their chromosomes and this expedites mapping disease associated genes and pathways. So now we can imagine having 100 cloned individuals, with an endless “n” per clone. You can use large numbers of mice per experiment/time point; you can combine data from different experiments because they are highly reproducible (same clone) etc.This slide shows how the mice are generated: The B6 are mated to D2 to generate F1 mice, which are all identical. The F1 mice are crossbred to generate the F2 population -- in this process recombinations in chromosomes take place in a random fashion such that each F2 mouse has different combination of the parental chromosomes. Because the genetic diversity of the F2 generation is random -- you cannot reproduce an interesting phenotype if you found it -- it is gone. So, now we randomly pair a male and female from the F2 and assign each pair as the new ancestors of teach of the RI lines. The progeny of the F2 parents are brother-sister bred for 20 generations at which point the chromosome is fixed and homozygosity is achieved for each line. Because the F2 parents were all genetically distinct, each of the derived BXD lines is also genetically distinct from each other, yet members of the same line are identical (inbred). The entire panel is 100 ( 40 regular RI 60 ARI). The ARI mice were derived by Williams et al in Memphis and they are more powerful than the RI mice because they have twice as many recombinations in their chromosomes and this expedites mapping disease associated genes and pathways. So now we can imagine having 100 cloned individuals, with an endless “n” per clone. You can use large numbers of mice per experiment/time point; you can combine data from different experiments because they are highly reproducible (same clone) etc.

9. The “Collaborative Cross” The effort to generate a much larger number of genetically disticnt inbred mice has been taken over by he complex trait consortium. There are 8, fully sequenced founder strains, and they are bred according to a scheme generated by ken manly to maximize random breeding and thus recombinations per chromosome. The breeding schema is shown in the slide. At the end you see a depiction of a typical chromosome from a mice, where each chromosome is a random mosiac of the founders. The CTC mice, like the BXD mice, will be fully genotyped and fully sequenced ( their parents are fully sequenced) and they have a much higher level of recombination -- this makes the mapping much faster and the ability to narrow down the genes in the mapped interval much smaller that it will be possible to identify your gene in a matter of days.The effort to generate a much larger number of genetically disticnt inbred mice has been taken over by he complex trait consortium. There are 8, fully sequenced founder strains, and they are bred according to a scheme generated by ken manly to maximize random breeding and thus recombinations per chromosome. The breeding schema is shown in the slide. At the end you see a depiction of a typical chromosome from a mice, where each chromosome is a random mosiac of the founders. The CTC mice, like the BXD mice, will be fully genotyped and fully sequenced ( their parents are fully sequenced) and they have a much higher level of recombination -- this makes the mapping much faster and the ability to narrow down the genes in the mapped interval much smaller that it will be possible to identify your gene in a matter of days.