Diseases: Sex Linked and Sex Influencedby Richard NixonHonors BiologyMrs. LindaDecember 19, 1994There are thousands of cases of sex linked and sex influenced diseasesworldwide. These diseases can range from a social inconvenience, to a fatalailment. In sex linked diseases, like Muscular Dystrophy, hemophilia and colorblindness, only males are affected.
When a man infected with a sex linkeddisease has children, all his sons are normal, but all of his daughters arecarriers. When a carrier woman and an uninfected man have children, half of thesons are normal, and half of the sons are affected; half of the daughters arecarriers and half of the daughters are normal. Only males are affected becausethe sex linked diseases affect the X chromosome. Males have one X chromosomeand one Y chromosome, so they need to use that X, whether it is flawed or not.Females on the other hand, have two X chromosomes, so if one is defective, theycan use their second X chromosome. Duchenne’s Muscular Dystrophy(DMD) isdefined as “a genetic disease characterized by defective muscle cells that cannot produce a protein called dystrophins (Science News 380). In patients ofhemophilia, there is a deficiency of a protein needed for blood clotting,causing this hereditary bleeding disorder.
In red/green color blindness, thebroadest form of color blindness that affects six percent of the population, thecones in the retina that receive green light do not function properly. Unlikesex linked diseases, sex influenced diseases are not reserved solely for themale. However, the diseases occur in males much more frequently than in females.This is because sex influenced diseases occur from imbalances in testosterone,much more highly concentrated in males. Baldness and gout are two diseases thatare a result of these hormonal imbalances.
Baldness is defined as the lack orloss of hair. Permanent baldness strikes on a hereditary basis because thehormonal imbalances tend to be passed from generation to generation. Gout is ahereditary metabolic disorder that involves recurrent acute attacks of severeinflamm ation of joints.
Sex linked diseases are born when sex genes, that compose two of the 46chromosomes, are mutated by an error in copying genes in reproduction. One ofthese sex linked diseases is Duchenne’s Muscular Dystrophy. DMD is a diseasethat has rightfully been gaining some headlines recently, as the disease istaking the lives of young children. Several cures have been brought up recentlyin the medical society, but none have paid any dividends. According to theMuscular Dystrophy Association, one in every 2500 boys are infected withmuscular dystrophy. The defective gene is found at the top of the X chromosome.
This gene is the largest known to exist. In patients of DMD, this gene iseither missing or severely mutilated. The symptoms of DMD are fatal.By ageeleven, the victims weaken fast. Normally, muscle deterioration begins in thelower legs and then moves up the body of the patient. Generally, victims are intheir early twenties when they die from either heart failure or diaphragmfailure.(The diaphragm is the muscle that makes breathing possible.
) One motherof a Duchenne’s Muscular Dystrophy patient says succinctly, “Eventually thesekids get bedridden and then they die.”(Grady 87) It is imperative to find acure for Duchenne’s Muscular Dystrophy so we can save the lives of thousands ofinnocent children.One of the major researchers working on a cure for DMD is Dr. Peter K. Lawof the Cell Therapy Research Foundation.
Law has been in the field for overtwenty years and has made many discoveries. In 1972, Law’s doctoral thesisproved that dystrophic muscle cells have abnormal cell membranes. This showedthat the disease was caused by a muscle defect, not a nerve defect as waspreviously thought. Since it was clear that it was a muscle defect, Law triedto transplant both whole and minced muscle into mice. The minced muscle provedto be too damaged to operate, and the whole muscle was so large that it diedbefore an adequate blood and nerve supply was developed.
At this point, sincethe whole muscle was too large but was the only feasible solution, he decided totransplant whole muscles of a baby mouse into an adult mouse. This muscle wasnot damaged, because it was not minced, and it was not too large, because thebaby muscle is considerably smaller than an adult muscle. Not only did themouse survive, but normal function was restored to diseased adult muscle.
Sincethe transplantation of muscle in mice was so successful, Dr. Law tried to findsomething along those lines that would work in a human. He found a solution;myoblasts. A myoblast is a mature muscle cell. It is a long thin fiber thatcan be more than an inch long. Unlike cells of other types, myoblasts have over200 nuclei.
When they are damaged, the myoblasts call upon a reservoir ofsatellite cells; small immature cells that nestle inside the muscle fiber’souter sheath. Satellite cells are the key to muscle repair and regeneration.Thesatellites leave the fiber, divide and then flatten into spindle shaped forms-the myoblasts. Myoblasts repair muscle cells by fusing with the injured cell andthey share their nuclei with the injured cell’s nuclei. When these twomyoblasts fuse completely, new cells are formed.In 1970 Law thought of a procedure that would fuse healthy myoblasts withthe dystrophic one, hoping that the resulting hybrid would have some function.
However, Law had to perfect this procedure. One of the main problems was thatwhen the healthy myoblast cells were fused, the immune system would treat themas alien and attack them. According to Law, another thing they had to do was”…
to design and perfect a culture medium to mass-produce myoblasts and weedout other cells.”(Grady 90) Law explains yet another problem encountered,”Ifyou cram too many cells in the same spot, they might not survive.”(Grady 90)While Law was working on his myoblast experiments, another door was openedby the discovery of the exact gene that caused the dystrophy. Many scientiststhought that this gene therapy, rather than Law’s cell therapy, was the future.
But Law dismissed gene therapy saying, “To me, in reality, that science will notwork in our lifetime. First you must make a normal copy of the defective gene,which is enormous, and somehow insert it into a small virus to carry it into thehost. Then you must hope that the virus will attack the right cell in the body,get through the cell membrane, break into the nucleus, and splice itself intoplace inside the cell’s DNA. And then you expect that cell to function asnormal? Are you kidding me?”(Grady 91-92) Law also made it clear that in genetherapy you have to replace the exact right nucleus in the exact right gene. Incell therapy, it doesn’t matter which is the exactly right one that needsreplacement because all of the cells are being replaced.Just two years after he wrote off the gene therapy, in 1988,when theproblems were weeded out, Law injected healthy myoblasts into 19 dystrophic mice.The results of these tests were encouraging; 11 mice fared extremely well, 3showed moderate improvement and 5 rejected the myoblasts.
Another encouragingfact was that the life span was increased from nine months to nineteen months inthe mice that fared extremely well. With the success in the mice, Law decidedto launch phase I of his human experiments . Each of three boys received fourinjections of myoblasts from either their brother’s body or their father’s body.In two of the boys, these injections, which were given in the foot, were matchedin the other foot by placebo saline solutions so nobody except Law’s assistantwould know which foot the real injections were placed.
At the end of theexperiment, all three boys said that they felt that one foot was stronger thanthe other. The foot that felt stronger was the same foot that was injected withthe myoblasts in all three cases, and all three feelings of greater strengthwere backed up by muscle strength tests administered by Law.Although the results of Phase I seemed ideal, Law received some criticismfrom his peers. They said that he rushed too quickly into the human experimentswithout gaining complete assurance that it would work to perfection. Somescientists were concerned that the myoblast injection would have side-effects.
The criticism was not publicized to a wide extent, and it went virtuallyunnoticed after Law made a statement in which he said, “We have to move theresearch forward as quickly as possible. These are dying children. We have notime to lose.
“(Grady 88)In May 1991, after Phase I was considered to be a success, Law lunchedPhase II. As of July 24, 1992 Law had treated the major leg muscle of 32 boys,ages 6 to 14. For this process, Law removes an eraser-sized piece of musclefrom either the patients father or brother. Then, he grows the muscle in thelab until he has 5 million myoblasts. At the time of treatment, the patients gounder general anesthesia for 10 minutes, and receive 48 injections of myoblastsin 22 muscle groups.
All patients take cyclosporin, an immune systemsuppressive for six months to prevent the boys from rejecting the myoblasts.The muscle strength of each patient is recorded 3 months before treatment, atthe time of treatment, and three months after treatment. This test was alsosuccessful.
Muscle strength was reported to improve in 43% of the muscles by anaverage of 41% when compared to muscle strength before treatment. 38% of themuscles stopped deteriorating after treatment and 19% completely failed torespond.However, as in Phase I, Law’s success was accompanied with criticism. Themajor problem his peers had was that there were no controls. Says Robert H.Brown Jr.
of Massachusetts General Hospital in Boston during one meeting session,”I am astonished that you haven’t controlled for cyclosporin.(Thompson 473) Lawcounters, “We have a perfect control, strength before and after transfer on thesame muscle.”(Thompson 473) Law also says that the upper body of the patientacts as a control. Law says that another reason he does not use controls isbecause the saline solution is shown to speed up deterioration, and that wouldnot be ethically correct. His opposition, however says that since he only hadtwo patients with the placebo solution, so those results could not be verified.Another thing that was criticized was the use of muscle strength to measure theeffectiveness.
The three major components of the criticism is that the childrenmay not be using full exertion, that when you get older your strength getsgreater, and third, how do you know dystrophin produced this strength; whatabout the cyclosporin?The work done by Peter Law has been exemplary. He has found a methodfor prolonging the life of young DMD patients. Although the way Law went abouthis trials were controversial, moving as fast as possible is imperative becausethousands of children are having their ability to walk, and eventually theirlives taken away by this disease. If Law had waited, it may have been too late.Although there is a large controversy concerning Peter Law, the MuscularDystrophy Association should support him and encourage him to perfect a cure forthis disease.Another sex linked diseases that is similar to DMD in makeup, not insymptoms is hemophilia.
In hemophiliacs, a protein that clots blood is missingor abnormal due to a gene mutation that was formed in the duplication of sexgenes. The protein missing in hemophilia victims is antihemophilic globulin(AHG). Like in all sex linked diseases, only males can show symptoms, andfemales are the only carriers. The father of a hemophiliac may or may not beinfected, but the mother must be a carrier. A hemophiliac has received hismother’s bad X chromosome and his father’s Y. The same couple can also have anormal son who received his mother’s good X and his father’s Y. If the couplehas daughters she can receive her father’s X and her mother’s bad X, or mother’sgood X.
So, the chance of a hemophiliac boy being born when the mother is acarrier is one in four. Therefore the incidence of hemophilia is familial, asin the Russian royal family. In hemophiliacs ,the tendency to bleed becomesnoticeable at a young age and leads to severe anemia or even death.
Hemophiliacs often have large bruises and soft tissue of the skin from incidentsas small as lightly bumping into something. This bruising is much like thebruising of the elderly. Not only will bruises form, but bleeding will oftenoccur for no reason in the mouth, nose and gastrointestinal tract.
Once thevictim grows out of childhood, hemorrhages in knees , ankles, elbows and otherjoints occur frequently. These hemorrhages result in swelling which impairs thevictim’s function. Hemophilia patients are generally advised to refrain fromphysical activity . When hemorrhages occur, local application such as thrombinare applied that serve as a blood clotting mechanism, or blood is transfused.
A third type of a sex linked disease caused by a defective chromosome iscolor blindness. Red/green color blindness, the most common type that affectssix percent of the population, is caused by defective green cones in the retina.People with red-green color deficiency see blue and orange very clear and bright.Other colors, although different from the colors that normal people see, arealways the same to them and suit most victims fine because they have nothing tocompare the colors they see to(USA Today 16). Like hemophilia, Duchenne’sMuscular Dystrophy and all sex linked diseases, only males suffer the symptoms,and the females are the carriers. Although color blindness is a disease thataffects thousands of people, it is not a life-threatening disease.
Most colorblind people do not suffer, because they do not know that the color should bedifferent. Few problems, like traffic lights, hinder color blind people, and asCynthia Bradford, an opthamologist at the University of Oklahoma Health Sciences Center says, “With many people, you might not even know they’re color blindunless they tell you”(USA Today 16)Unlike sex linked diseases, sex influenced diseases do not affect onesex solely. Baldness, the lack or loss of hair, is caused by an imbalance oftestosterone.
Since it is caused by testosterone, much more concentrated inmales, sex influenced diseases are much more common in males.This imbalancecauses the destruction of hair follicles which causes the baldness to bepermanent. The largest type of baldness is male-pattern baldness that affectsforty percent of some male populations(Norton 2:826). Male-pattern baldness ishereditary, and varies in degree from generation to generation. Ironically,people with male pattern baldness have a higher percentage of body hair thanmost, and those Aborigines with male pattern baldness generally have bald calvesas well.
Although this disease is not life-threatening, baldness is a socialproblem. Almost every other man is a victim, and those who do suffer thedisease are prejudiced. Solutions, not cures to baldness to exist. The firstobvious option is the wig. Secondly, hair transplants are becoming more andmore frequent, and topical solutions such as minoxidil have helped to preventfurther balding in many cases, and reinitiate hair growth in a much smallerpercent of users.
The important thing to remember about sex influenced diseasesis that they are hereditary, but only to the extent of the amount oftestosterone produced. The genes tell the offspring the amount andconcentration of testosterone, not whether or not to lose hair. If the amountsof testosterone relayed are not normal, baldness may occur.A second sex influenced disease is gout. Gout is the “hereditary metabolicdisorder that is characterized by recurrent acute attacks of severe inflammationin one or more of the extremities”(Norton 5:392). This inflammation is causedby an excess deposition of uric acid in and about the joints. Like baldness,this condition strikes men predominantly, but can also be found in women.
Theexact cause of gout is not yet known, however, it is logical to believe that itis caused by the same hormonal imbalances as baldness, and that is why it isclassified as a sex influenced disease. Gout is inborn, however the symptoms donot occur until middle age. Before the attacks, small amount of uric acid buildup in the joints. All joints, especially the big toe, are susceptible.
Symptoms such as heat, redness of the skin, and extreme tenderness and painaccompany the affected joints. Numerous gout attacks can cause knobby bumps onthe affected joints. Acute cases of gout may come and go in a matter of a weekfor no apparent reason. Some circumstances , however, inhibit the symptoms ofgout. These circumstances include: emotional upset, diuresis, surgery, trauma,and the administration of certain drugs.
Cochicine is the classic treatmentfor gout, but new medicines have surfaced recently.Sex linked and sex influenced diseases are a problem that hurts our society.Although many of the diseases are just an inconvenience, others are fatal.
There is no fathomable way of preventing any of these diseases, unless genes canbe altered. The only medicine to treat theses diseases acts as a suppressant,not as an end to the diseases’s life. Hopefully, cures can be found to save thelives of young, innocent people who are affected with hemophilia, Duchenne’sMuscular Dystrophy and other fatal diseases.Works Cited”Color Blindness Misconceptions.” USA Today 120 (1992):16 “Foot Feat:transplant treats dystrophy.
” Science News 16 June 1990:380 Grady, Denise.”One foot forward.” Discover September 1990:86-93 Massie, Robert., and Massie,Suzanne.
Journey. New York: Alfred A. Knopf, 1961. Norton, Peter B.”baldness.” The New Encyclopedia Britannica. 1994 ed.
Norton, Peter B. “gout.”The New Encyclopedia Britannica. 1994 ed. Norton, Peter B.
“hemophilia.” TheNew Encyclopedia Britannica. 1994 ed. Thompson, Larry.
“Cell transplant resultsunder fire.” Science 257 (24 July 1992) 472-474