10.7554/eLife.01754.007 Figure 4. Structural mapping of mutations that interfere with binding and CD4 downregulation.
Through the use of genetic models systems and the mapping of mutations that cause human diseases, it has been well-established that errors in these processes underlie a wide range of maladies, including birth defects, cancer, kidney disease, and neuronal degeneration.
Therefore, we modeled the RIP1 DD structure based on the structure of Fas DD (PDB id 3OQ9) and mapped the mutations that might disrupt the formation of the RIP1 DD/FADD DD complex on the modeled structure of RIP1 DD.
Map positions of mutations that were mapped in our project and cloned by other researchers are shown together with the ZMAP positions of the affected genes (publicly available from ZFIN [10]).
Except lin(bh25) and unc sy5415), all other loci were uniquely assigned to linkage groups by standard 2-factor mapping using known mutations that serve as reference (Table 6, also see [ 21]).
ATRX was discovered to map the genetic mutations that lead to the ɑ-thalassemia, mental retardation, X-linked (ATRX) syndrome (Gibbons et al., 1995).
We mapped coding sequence mutations that are unique to the DT40 genome; mutations inactivating the PIK3R1 and ATRX genes likely contributed to the oncogenic transformation.
We report here c-CBL mutations that mapped not only to the RING finger domain, but also to the TKB domain, proline-rich domain and the C-terminal region, but none mapped to the linker region as reported in the AML studies described above [23], [24], [25], [26], [29].
This was in the 1980s, and molecular biology was just beginning to take off, so it quickly became feasible to map and identify the mutations that could complement the phenotyping studies we had already done.
