KEY 2005 7 03 Problem Set 7 KEY NO DUE DATE This problem set is to provide practice on concepts from lectures 30 36 1 The following pedigree shows the inheritance of an autosomal recessive trait in a specific family This trait is caused by a specific allele g at the G g locus You have some reason to suspect that the G g locus is linked to an SSR on chromosome 6 called SSR41 You obtain blood samples from each member of the family and perform a PCR reaction on the DNA of each individual that allows for the genotyping of SSR41 The results of the PCR reactions are shown below each family member in the pedigree in a schematic of an agarose gel in which you have loaded the PCR reactions from each family member into a separate well in the gel A allele B allele C allele D allele paternally inherited allele at SSR41 C C D C C D maternally inherited allele at SSR41 B C B B C C paternally inherited allele at G g locus g g g g g g maternally inherited allele at G g locus g g G G g g a Fill in the tables above to indicate which alleles have been passed on to each child from their mother and father 1 KEY b Whose alleles the mother s or the father s or both should you follow to calculate the LOD score for the linkage of the SSR to the G g locus You want to follow the alleles of the parent who is heterozygous at both the disease locus and the SSR locus so you can tell which of the children are parental and which are recombinant In this case that parent is the mother c Draw all possible phases for the parent s you listed in part b G g B C inherited from grandpa inherited from grandma Since you know the genotypes of the mother s parents there is only one possible phase for the mother d For each phase you drew you drew in part c state how many children are recombinants and how many children are parentals given that phase GB from mother gC from mother GC from mother gB from mother parental parental recombinant recombinant Therefore child 1 is recombinant the other 5 are all parental e Calculate the LOD score for this family at theta 0 04 for the linkage of the SSR to the G g locus For the numerator of the odds ratio you assume that the SSR and G g locus are linked Since theta 0 04 this means you d expect 4 recombinants and 96 parentals There are two types of recombinants GC and gB Each type of recombinant will occur at equal frequencies so there is a 2 chance of any child getting GC from the mother and a 2 chance of any child getting gB from the mother Each type of parental will occur at equal frequencies so there is a 48 chance of any child getting GB from the mother and a 48 chance of any child getting gC from the mother Chances of the mom creating each type of gamete GB 48 gC 48 GC 2 gB 2 2 KEY Child one got Bg The chance of this is 2 Child one got Cg The chance of this is 48 Child one got BG The chance of this is 48 Child one got BG The chance of this is 48 Child one got Cg The chance of this is 48 Child one got Cg The chance of this is 48 The chance that you saw these six kids would be 2 48 48 48 48 48 For the denominator of the odds ratio you assume that the SSR and G g locus are NOT linked UN linkage corresponds to theta 0 5 because UN linkage gives 50 parentals and 50 recombinants Since theta 0 5 this means you d expect 50 recombinants and 50 parentals There are two types of recombinants GC and gB Each type of recombinant will occur at equal frequencies so there is a 25 chance of any child getting GC from the mother and a 25 chance of any child getting gB from the mother Each type of parental will occur at equal frequencies so there is a 25 chance of any child getting GB from the mother and a 25 chance of any child getting gC from the mother Chances of the mom creating each type of gamete GB 25 gC 25 GC 25 gB 25 Child one got Bg The chance of this is 25 Child one got Cg The chance of this is 25 Child one got BG The chance of this is 25 Child one got BG The chance of this is 25 Child one got Cg The chance of this is 25 Child one got Cg The chance of this is 25 The chance that you saw these six kids would be 25 25 25 25 25 25 LOD log of the odds ratio log 10 0 48 5 0 02 1 0 32 0 25 6 3 KEY f At what theta value would you achieve the maximal LOD score for this family knowing everything you know about them You d expect to achieve the maximal LOD score when theta the fraction of recombinant children that you actually have in your family In this case 1 in 6 children were recombinant so you d expect the maximum LOD score when theta 1 6 0 17 g What is the LOD score value for the theta value you listed in part f If theta 0 17 you d expect 83 total parentals and 17 total recombinants log 10 0 42 5 0 08 1 0 63 0 25 6 h If you had never seen the genotyping results for this family and only had their pedigree available what would have been the theoretical maximum LOD score value that you could have ever calculated for this family Hint Start by thinking about which theta value could give you the maximum possible LOD score The theoretical maximum LOD score for an SSR and a trait locus from a 6 child family in which there is one relevant parent whose phase you do indeed know occurs if all children are parentals If all children are parentals then the optimal LOD score value would occur at a theta 0 Thus the theoretical maximum is log 10 0 5 6 1 8 0 25 6 i If you had never seen the genotyping results for this family and only had their pedigree available what is the minimum number of kids that the family would have had to have contained in order to reach a theoretical maximum LOD score that is 3 log 10 0 5 x 3 0 25 x Solving for x x at least 10 children 4 KEY 2 A tumor results when a cell in the body loses control over cell growth and division such that the cell divides many times forming a ball of cells Cancer can be extremely harmful to the organism when these …
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