Page 80 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

72 Chapter 3 Extensions to Mendel’s Laws

GENETICS AND SOCIETY Crowd: © Image Source/Getty Images RF

Disease Prevention Versus the Right to Privacy
In one of the most extensive human pedigrees ever assembled, Figure A Pedigree showing the transmission of
a team of researchers traced a familial pattern of blindness back juvenile glaucoma. A small part of the genealogic tree: The
through five centuries of related individuals to its origin in a vertical transmission pattern over seven generations shows that
couple who died in a small town in northwestern France in a dominant allele of a single gene causes juvenile glaucoma.
1495. More than 30,000 French men and women alive today The lack of glaucoma in V-2 followed by its reappearance in
descended from that one fifteenth-century couple, and within VI-2 reveals that the trait is incompletely penetrant.
this direct lineage reside close to half of all reported French I
cases of hereditary juvenile glaucoma. The massive genealogi- 1 2
cal tree for the trait (when posted on the office wall, it was over II 1 2
100 feet long) showed that the genetic defect follows a simple
Mendelian pattern of transmission determined by the dominant III 1 2
allele of a single gene (Fig. A). The pedigree also showed that Male
the dominant genetic defect displays incomplete penetrance. IV 1 2 Female
Not all people receiving the dominant allele become blind; Blind
these sighted carriers may unknowingly pass the blindness- V 1 2 3 4 5 6 without diagnosis
causing dominant allele to their children. Glaucoma
Unfortunately, people do not know they have the disease VI
until their vision starts to deteriorate. By that time, their optic fi- 1 2 3 4 5 6
bers have sustained irreversible damage, and blindness is all VII
but inevitable. Surprisingly, the existence of medical therapies 1 2 3
that make it possible to arrest the nerve deterioration created a
quandary in the late 1980s. Because effective treatment has to
begin before symptoms of impending blindness show up, infor- By 1997, molecular geneticists had identified the gene
mation in the pedigree could have helped doctors pinpoint whose dominant mutant allele causes juvenile glaucoma. This
people who are at risk, even if neither of their parents is blind. gene specifies a protein called myocilin whose normal function
The researchers who compiled the massive family history there- in the eye is at present unknown. The mutant allele encodes a
fore wanted to give physicians the names of at-risk individuals form of myocilin that folds incorrectly and then accumulates ab-
living in their area, so that doctors could monitor them and rec- normally in the tiny canals through which eye fluid normally
ommend treatment if needed. However, a long-standing French drains into the bloodstream. Misfolded myocilin blocks the out-
law protecting personal privacy forbids public circulation of the flow of excess vitreous humor, and the resulting increased pres-
names in genetic pedigrees. The French government agency sure within the eye (glaucoma) eventually damages the optic
interpreting this law maintained that if the names in the glau- nerve, leading to blindness.
coma pedigree were made public, potential carriers of the dis- Knowledge of the specific disease-causing mutations in the
ease might suffer discrimination in hiring or insurance. myocilin gene has more recently led to the development of diag-
France thus faced a serious ethical dilemma: On the one nostic tests based on the direct analysis of genotype. (We de-
hand, giving out names could save perhaps thousands of peo- scribe methods for direct genotype analysis in Chapter 11.)
ple from blindness; on the other hand, laws designed to protect These DNA-based tests can not only identify individuals at risk,
personal privacy precluded the dissemination of specific names. but they can also improve disease management. Detection of the
The solution adopted by the French government at the time mutant allele before the optic nerve is permanently damaged al-
was a massive educational program to alert the general public lows for timely treatment. If these tests become sufficiently inex-
to the problem so that concerned families could seek medical pensive in the future, they could resolve France’s ethical dilemma.
advice. This approach addressed the legal issues but was only Doctors could routinely administer the tests to all newborns and
partially helpful in dealing with the medical problem, because immediately identify nearly all potentially affected children; pri-
many affected individuals escaped detection. vate information in a pedigree would thus not be needed.

each gene, two alleles exist; a 0 allele that contributes tween pure-breeding plants carrying only 0 alleles at each
nothing to height and a 1 allele that increases the height of height gene and pure-breeding plants carrying only 1 al-
a plant by one unit. All alleles exhibit incomplete domi- leles at each height gene? If only one gene were respon-
nance relative to alternative alleles of the same gene. The sible for height, and if environmental effects could be
phenotypes determined by all these genes are additive. discounted, the F 2 population would be distributed among
0 0
What would be the result of a two-generation cross be- three classes: homozygous A A plants with 0 height (they