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What can you conclude about the gene(s) encoding VH and CH?

Recall that allelic forms of Ig constant regions exist. In the mouse, the locus encoding Ig heavy chain constant regions is named IgH. The inbred mouse strains BALB/c and C57BL/6 have different IgH alleles: BALB/c mice are IgHa and C57BL/6 mice are IgHb. They also differ in their humoral response to phosphorylcholine (PC). While both strains make equivalent amounts of PC-specific serum antibody, the response in BALB/c mice is dominated by antibodies with a VH region called "T15," which can be detected with an antiserum (anti-T15). In contrast, the PC-specific antibodies made by C57BL/6 mice don't use the T15 VH.
In the early 1970's it was suggested that variable and constant regions were encoded by SEPARATE GENES! To investigate the genetic relationship between V-region and C-region genes, two researchers typed the mice listed in the table below for IgH, then immunized the mice with PC-BSA. They assayed the resulting PC-specific responses for T15 VH by testing dilutions of each mouse's serum for precipitation with anti-T15. The results are shown in the table (attached)
? What can you conclude about the gene(s) encoding VH and CH?
? Do these data disprove the hypothesis that V and C regions are encoded for by separate genes? Explain your reasoning.

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Solution Preview

If two genes are linked, they always segregate together. In this case, making the antibody would always appear in the mice with IgHa and not making an antibody would be with the IgHb. Let's see what we have by drawing out the crosses along the way.

F1: a+ X b- = ab+-

x a+
b- ab+-

F2: ab+- X ab+-

Not linked: the possible alleles are a+, a-, b+, b-
Drawing out ...