Page 407 - Carrahers_Polymer_Chemistry,_Eighth_Edition

370 Carraher’s Polymer Chemistry

receptors and the immunoglobulins. The gene segments encoding the amino-terminated part of the
immunoglobulin proteins are also quite susceptible to mutation. The result is a collective popula-
tion of B cells within most of us with the ability of producing the needed vast number of antibodies.
Thus, gene variety is produced near to the event of our conception.
As noted before, a single gene may play several roles, or at least the proteins derived from them
may. Several genes have been associated with the early onset of Alzheimer’s disease, two found on
chromosome 14, one on chromosome 21, and interestingly one on chromosome 19, none other than
APOE. It is not unexpected (many results are not unexpected after the fact) that a blood-lipid related
gene is associated with a brain disease. It has been found for some time that those with Alzheimer’s
disease had high cholesterol levels. Again, the bad actor is the E4 variety. For those families that are
prone to Alzheimer’s disease, those with no E4 gene have about a 20% change of contracting the dis-
ease; those with one E4 almost 50% with a mean age of 75 for onset; and those with two E4 genes,
the probability is more than 90% with the mean age of onset about 68 years of age. Other genes also
affect the incidence of Alzheimer’s disease. For instance the incidence of contracting the disease is
much higher for whites with the same E4 amounts in comparison to blacks and Hispanics.
th
The difference between E4 and E3 is a signal base pair, the 334 base pair with the E4 having a
G instead of an A.
The body is a marvelous “machine,” growing and learning, and performing its own maintenance.
Much of this maintenance is a sort of self preservation or self protection to maintain its own original
molecular design. Involved with much of this are DNA repair enzymes that continuously monitor
the genome to correct damaged nucleotides and nucleotide sequences that are damaged through

self-inflected mutations or through environmentally related damage such as exposure to various
chemical agents and radiation. There are currently about 150 known human DNA repair genes
where the function (or at least one function) is know along with its location within the genome.
The particular sequence is also known for most of these. The sequences for many of these have
been know for several years but the specific location and proximity to other genes has only become

known with the recent human genome project. These repair genes perform a number of functions.
MSH2 and MSH3 found on chromosomes 2 and 5 are involved with mismatch and loop recognition
repair; a group of genes known as fanconi anemia (FAN) genes, are found on chromosomes 3, 6, 9,
11, 16, and so on and are involved with repair of DNA cross-links; and so forth. The overall shape
of these DNA repair proteins is rapidly being uncovered and active sites being identifi ed.
Now let us look briefly at an aspect of aging. We are given, or so we are told in literature, our

four score or 80 years. We are not able to describe why eighty, but can comment on why this num-
ber is not much larger. The human genome is much longer lived and its copying has occurred many
times. Yet the cells in our body have only replicated a few times in comparison. Even the more
active cells have replicated only several hundred times. Part of the answer resides on chromosome
14 in a gene called TEPI. This gene forms a protein that is part of the telomerase system. Lack of
telomerase causes senescence. Addition of telomerase allows some cells a much longer lifetime.
Telomers, produced by telomerase, occur at the end of chromosomes. These telomers are included
in the so-called junk with a seemingly uncoded sequence, TTAGGG. This sequence is repeated
many times. This sequence is the same for all mammals and is the same for most living species.
Typically, each time the chromosome is reproduced, the number of “telomer sequences” decreases,
at the average rate of about 30 base pairs a year, and may be partially responsible for the various
cells “wearing out.” By the time we reach our four score years, we have lost about 40% of the
telomer sequences.
The telomerase contains RNA, which is used as the template for making telomeres, and a protein
part that resembles reverse transcriptase, the enzyme responsible for the production of transposons
and retroviruses. Telomerase acts to repair the ends of chromosomes relengthening the telomere
ends. Thus, the lack of telomerase appears to cause the ageing and eventual death of at least some of
our cells. The relation to aging is much less certain, and surely more complicated. Thus, those with
Werner’s syndrome, where rapid aging occurs, start out with the same average length of telomers,

9/14/2010 3:41:27 PM
K10478.indb 370 9/14/2010 3:41:27 PM
K10478.indb 370