1. Sticky finger disease (Sf) has been found to be the major cause of kleptomania in the United States. The disease segregates as an autosomal recessive trait.

    1. Briefly describe how you would use a set of random clones from a human genome library to identify sequences that map close to the Sf gene. Be sure to indicate what makes a clone useful for this purpose. 

    2. One such clone is found and used to screen the DNA from a number of different mouse/human hybrid lines with the following results. Use the data to determine the chromosomal location of the Sf gene. (+ indicates that the indicated human chromosome is found in the cell line and that the DNA from the line hybridizes to the cloned probe.)

Chromosome

Probe

Cell line

1

2

3

5

6

7

9

10

14

16

18

+

1

-

+

-

-

-

+

+

-

+

-

+

-

2

+

+

-

-

-

+

+

+

-

-

-

-

3

+

-

-

-

+

-

+

+

-

+

-

+

4

-

+

+

+

-

+

-

-

+

-

+

+

5

-

-

+

+

-

+

+

+

+

-

+

+

6

-

+

+

-

-

-

+

+

+

-

+

-

7

+

-

-

+

-

-

+

+

-

+

+



    1. You find that a second clone also lies near the Sf gene and you test both as probes against DNA from families with Sf individuals. Examine the following lod scores and state which clone you would use for genetic counseling and why you would use tha t clone.



Recombinant fraction

0.00

0.05

0.10

0.20

0.30

0.40

clone A

1.21

2.42

3.20

2.01

0.53

0.22

clone B

3.94

1.98

1.15

0.79

0.21

-0.60



    1. A couple comes to you for genetic counseling, because both husband and wife come from families with individuals with Sf disease. From your previous studies of the disease you know that a number of different mutations have arisen in the gene through time. Thus, it is probably not a good idea to test only the DNA from the husband and wife.

      1. Why? 

      2. What information would you need to adequately counsel the couple? 

     

  1. Answer TRUE or FALSE.  If the statement is TRUE, explain or give a supporting example.  If the statement is FALSE, either correct the statement or give a counterexample. 

    A LOD score of -3 shows statistically significant linkage.

     

  1. Explain the following:

    1. How polymorphisms can be used to determine the map position of a gene on a C. elegans chromosome.

    2. How LOD scores can be used to determine the significance of the mapping of a human disease gene.

     

    Answers