(1) people who are asymptomatic, but carry a gene that increases the probability that they will develop the disease.
(2) individuals who are heterozygotes (carriers) for some recessive or X-linked genetic condition, but who remain asymptomatic
(3) individuals with one or more genetic polymorphisms that are not known to cause any medical condition
(4) imediate relatives of individuals with known or presumed genetic
diseases.
People in category 1
(a) individuals with conditions that can be treated before the symptoms become manifest, so that the disease is not disabling (PKU)
(b) individuals whi in the future will be affected by unteatable and fatal conditions (Huntington's disease)
(c) individuals who have diseases that vary in the severity or the effectiveness of the treatment
(d) individuals who have genes that do not necessary lead to disease, but could increase the probability of a disease (cancer, diabetes, heart disease)
(e) individuals whio have genes that make them suscepatable to envirnmental
factors or toxins.
2. Male and female carriers of autosomal recessive traits, as well as
women who are carriers of X-linked diseases.
3. Individuals with benign genetic polymorphisms (e.g. blood group polymorphisms)
Think about groupings for points
2 and 3
TYPICAL PATHWAYS -selection
| ATP | |||
| ^ | |||
| dADP | |||
| ^ | |||
| AMP | <---ARPT
**8 aza A **6 diaminopurine |
<-------<---ADENINE + PRPP | |
| ^ | |||
| adenosuccinate | |||
| ^ | |||
| de novo pathway | ^ (arrow up) | ||
| PURINE---11 ENZYMES + PRPP BIOSYNTHESIS | -->IMP <-- | <...HGPRT-
**8 AZA A |
<---HYPOXANTHINE |
| **AMINOPTERIN | v (arrow down) | ||
| v | |||
| XMP | |||
| v | |||
| GMP | <-----HGPRT
** 8 AZA A OR 6 THIOGUANINE |
<---GUANINE + PRPP | |
| v | |||
| GDP | |||
| v | |||
| dGTP |
NOTES: 1) Any of the drugs** can kill normal cells because they enter the pathways as analogues of a normal component
2) 8 AZA A or 6-Thioguanine (examples)
cannot enter the pool IF HGPRT is absent
=======================
A few notes and diagrams concerning HAT
HAT MEDIA contains hypoxanthine,
aminopterin and thymidine
| dUMP-------------------> | dTMP-->--->---> | DNA |
| *AMINOPTERIN | ^ | |
| TK |
A normal cell will grow in the presence of aminopterin IF thymidine is present
Remember that hypoxanthine has to
be present for IMP synthesis in the presence of the an aminopterin block
In conditions of NO SELECTION, thymidine
kinase is not necessary because it could be formed from dUMP
NOTE: TK- cells cannot use thymidine
or BUDR