Reading assignment

Reading assignment

The common house mouse, Mus musculus, is a model organism for human diseases. As such, it has been recently utilized in QTL mapping to see which genes may contribute disproportionately to disease states. Unfortunately, because of its high rate of inbreeding and bottleneck effect when it was first developed as a model organism, it displays a high level of linkage disequilibrium such that QTLs can span 20-40 cM, containing hundreds of genes. This is a problem on two levels: One, while this resolution is great relative to the “double crossovers” of Morgan’s flies, it leaves much to be desired

in terms of quickly discovering traits that contribute to disease states. Two, using inbred lines such as mouse decreases verisimilitude—we’re trying to see how diseases work in humans, we should use animals with same genetic variance as humans. This is especially relevant because mice colonized the world with humans, and as such may show similar patterns of gene evolution and population structure. These authors found that QTL maps can be made to the resolution of 1 cM (about 100 kB in M. musculus) by using the wild conspecifics of these lab mice. In doing so,

they also found that wild mice have much lower rates of LD, comparable to humans. They do show a lot of homozygosity, which the authors attribute to some inbreeding and previous bottlenecks. The authors suggest that using wild mice to develop finer mapping resolution for QTLs, especially because they can use the same SNPs that they use for laboratory mice. That is to say, we can use the same tools available to us in lab mice on wild mice for experiments more relevant to populations of humans, as opposed to individuals. Questions: 1) Wild mice have a lot of homozygosity.

Would wild mouse populations (new world field mice, etc. ) show less homozygosity, and can we use them in these experiments when homozygosity somehow impedes the resolution of the mapping? 2) The text keeps saying that African populations are in a state of high linkage disequilibrium, and I’m assuming it is because they are in reproductive isolation. If mice are commensal with Africans as they are with other human populations, do they exhibit the same LD? Can we then use them as a model to look at disease states and disease traits in Africans?

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