They had met four years earlier in the hemophilia clinic where Greg was waiting for his brother Jeff to get an injection of factor viii, a protein that helps the blood to clot. When a person’s factor viii level is very low (less than normal), even the smallest cuts can be troublesome and uncontrolled internal bleeding is common. Complications include swelling, joint damage, and an increased likelihood of neurological complications due to antibacterial bleeding. Even simple surgical procedures such as tooth extractions become far more risky. Jeff condition was noted by his Trinitarian shortly after birth when his circumcision bled profusely.
Since then, Jeff has received monthly injections of factor viii, either at home or (twice a year) at a clinic where his physical condition is reviewed by a physician’s assistant. At first these injections contained clotting factor isolated from the blood of human donors but, for the last 7 years or so, he has received recombinant clotting factor, which is genetically engineered. It was in that clinic waiting room that Greg struck up a conversation with Olga, who was waiting for her uncle to finish his exam and receive an injection of clotting factor. Like Jeff, Alga’s uncle also suffered from hemophilia A due to factor viii deficiency.
Beginning with this common experience, Jeff and Olga quickly fell in love and were married the following year. They are now thinking about starting a family of their own, but are concerned about the risks of passing on genetic diseases to their children. They know for example that hemophilia A is an inherited disease, and several of Serge’s relatives suffer from monotonic dystrophy, a muscle weakening disease that also runs in families. As a first step, the genetic counselor has asked them to fill out a reiterative history listing their relatives, relationships, and if they were affected by any genetic diseases that they know of.
The forms are seen below. NAME: Greg have one brother and one sister, neither of whom are married. My brother suffers from factor VIII deficiency, but no one else in my family does. My mother has two brothers and one sister. One of my uncles and one of my aunts are affected by monotonic dystrophy. My affected aunt married an unaffected man and they have a young, seemingly unaffected daughter. My other uncle is unaffected, as is my mother. Our primary care doctor has said that because both y mother and uncle are over fifty years old and show no symptoms, they do not have the disease. My father is completely normal.
He was adopted from an orphanage and nothing is known about his family. My maternal grandmother was an only child who also suffered from monotonic dystrophy. Her husband (my grandfather) was one of seven children (four boys and three girls). No one in the family seems to know much about the health status of my grandfather or his brothers. Both of my parents are alive but all of my grandparents are deceased. NAME: Olga have two brothers, one of whom has factor VIII deficiency. The brother with he disease is married to a woman who does not have the disease. They have two young boys, both normal.
My father is an only child who does not suffer from anything and his parents also are only children who do not suffer from any diseases. They are all still living. My maternal grandmother is healthy and had a sister who died just after birth. She married my grandfather who was one of four children, all boys, none of whom were affected by any disease that anyone is aware of. My grandparents had two children, my mother and my uncle. My uncle has hemophilia but my mom doesn’t. My uncle married my aunt (who is unaffected) and they had two children, neither of whom showed any sign of any disease.
Their boy is still single but their girl got married, to a normal man, and had a son, who has hemophilia A. Meeting with the Genetic Counselor “Good afternoon” said the woman rising to greet them, “I’m Dry. Eclectic. It’s good to finally meet you in person. ” “Nice to finally put a face to the voice. I’m Greg and this is my wife Olga. ” “Nice to meet you,” Olga said, taking a seat across the desk from Dry. Eclectic. “This whole having-kids thing is more nerve-wracking when you really start to think about it. ‘You’re doing exactly the right thing. There is no sense in worrying about things unless you have to.
Maybe I can set your mind at ease a little bit. To begin with, I know that you’re both concerned about factor viii deficiency and monotonic dystrophy because of the family history. Is there anything else that you’d like to know? ” “Well,” began Olga, ‘the fact that we both have these diseases in our family and there is a chance that we could pass them on to our children has opened our eyes a little bit, but we’d also like to know if you can predict other diseases that don’t run in our family. Like my best friend n high school had cystic fibrosis and she died when she was only twenty four, and was sick almost all the time. “Okay, well, cystic fibrosis doesn’t look like it is in either of your family histories so it’s probably not worth worrying about. But, we can spend a little time going over the chance that you both carry a gene that has never before shown its face. The first step is we have to convert the family information you two have provided into a graphical representation called a pedigree. From there we can begin to correlate family relationships with the appearance of specific diseases. ” Answer Question #1 Part 2?Autocross Dominant Traits “Great, so this looks like an accurate representation of your family, right? Dry. Eclectic asked. “Looks good to me,” replied Greg. “My family is so small, there’s not much to miss until you get to my grandparents,” said Olga. “Well, factor viii deficiency and monotonic dystrophy are inherited in completely different ways. Come to think of it, you asked about CB as well and “CB? ” asked Greg. “Cystic fibrosis,” Dry. Eclectic continued. “l was about to say that cystic fibrosis is inherited in a manner different than both of the other diseases you are concerned about, but let’s tackle them one at a time. Monotonic dystrophy is an autocross dominant disease and it is the easiest to pick out of a pedigree. Now Greg, even though you have an uncle and aunt as well as a grandmother who all have the disease, you don’t and there is no way that you will pass this disease on to your children. So that is the first piece of good news. ” “But don’t a lot of genetic diseases skip a generation? ‘ Greg asked. “And even if doesn’t, my mom has two siblings with the disease. Could she be a carrier and just pass the disease on to me? For that matter, could I be a carrier? “Yes, could he be a carrier? ” Olga added. Absolutely not,” Dry. Eclectic said. “Let me show you why. ” Answer Questions #2-5 Part 3?Autocross Recessive Traits “Well, I certainly feel better about that,” said Greg. “l guess there is no reason to worry about passing on MD to our children. They’ll just have to worry about inheriting their father’s incredible good looks, fabulous sense of humor, creativity ” “And modesty Hold on a second, God’s gift to the world,” Olga chimed in. ‘We still haven’t talked about factor viii deficiency, which is why we came here in the first place. “Well,” Dry. Eclectic began, “factor viii deficiency is what’s known s a sex-linked disease. Before we get to that, let’s take a look at a disease with a slightly simpler mode of inheritance. Many traits, whether or not they are considered to be diseases, are described as autocross recessive traits. These are the ones you alluded to earlier when you talked about diseases that skip generations and about people being carriers. Some common recessive traits include albinism, sickle cell disease, and cystic fibrosis, which I promise we will get to, Olga.
Now, let’s look at some of the rules governing these types of traits. ” Answer Questions #6-9 Part 4?Sex-Linked Inheritance Aright,” Olga began, “so factor viii deficiency is sex-linked because it only affects men. Does it require the presence of testosterone or something like that? “No, but there are many traits that do depend on the presence or absence of sex hormones. We call them sex-influenced traits. Sex-linked traits get their name from the fact that the genes that cause them are carried on the X chromosome, which is one of the chromosomes responsible for determining what sex a person will become.
Let’s take a look at how factor viii deficiency runs in both your families. ” Answer Questions #10-14 Part 5?Unsettled Issues So, is it possible to test for each of these diseases? ” asked Greg. “Yes, but for the sake of practicality, or expense, as some would say, we only test for those diseases that are reasonably likely based on a patient’s history. We wouldn’t for example test either of you for the presence of the CB allele. ” “Wait a minute,” Olga began, “what about a disease that doesn’t show up until later in life.
Serge’s uncle didn’t show any symptoms of monotonic dystrophy until he was something like forty … ” “Forty three,” Greg corrected. ‘Yeah, anyway, if a genetic test shows that you are going to get a genetic disease ND it becomes part of your medical history, could an insurance company exclude it as a pre-existing condition, even though you don’t have it yet? ” ‘Well, the law is actually quite unsettled about the issue. Genetic testing has the power to predict the occurrence, or at least the likelihood of occurrence, of many diseases?cancer, Alchemist’s disease, and diabetes just to name a few.
Many people are not comfortable with that information being part of their medical records because they are afraid it could lead to a loss of insurance, losing out on a job, or some other form of discrimination. But,” Dry. Eclectic said with finality, “that is a subject to take up with lawmakers. It is entirely possible that after the conversation we’ve just had that you two know far more about the subject of genetic testing than your congressman or senators. If you’re concerned about the legal ramifications of genetic testing, you should let them know. It was a pleasure meeting both of you. “Likewise, Doctor. You really helped to put my mind at ease,” Olga said. “Yeah, I think we both feel a lot better, thanks,” said Greg. Answer Questions #15-17 Questions part 1 1 . What would a pedigree of Greg and Alga’s families look like? Construct the pedigree and concentrate simply on family relationships and affected persons. Serge’s Family Pedigree: Greg is the square outlined with red MD = monotonic dystrophy VII = factor VIII deficiency H = hemophilia Orange fill in = carrier for factor VIII Alga’s Family Pedigree: Olga is the circle outlined with red Resources http://education-portal. Mom/academy/lesson/pedigree-analysis-in-human -genetics-tutorial. HTML link to -7 min tutorial on creating a pedigree chart Part 2 2. Do autocross dominant disorders skip generations? No, because autocross dominant disorders do not skip generations. . Could Greg or his mother be carriers of the gene that causes monotonic dystrophy? No, Greg and his mother don’t have the disorder therefore they wouldn’t be carriers of it. 4. Is there a possibility that Serge’s aunt or uncle is homozygous for the monotonic dystrophy (MD) gene? No, there is not a possibility.
Serge’s grandmother would have also had to to be homozygous for the MD gene. You know that she is not homozygous because her husband did not have MD and only two of their four children have the disorder. 5. What is the possibility that Greg and Alga’s children could inherit the MD gene? Neither Greg nor Olga have MD so there is no chance that their children will. Human Genetics for First Year Students: Pedigree Construction http://www. OIC. Du/chaises/bums/bimbos/lessons. HTML -genetics-inheritance-patterns. HTML -11 min tutorial on interpreting pedigree Part 3 6. What are the hallmarks of an autocross recessive trait? . The traits are found in the siblings of the person that is affected, but not in the parents or the children of that person (it skips generations). 2. Females and males are equally likely to be affected 3. It has been found that the recurrence risk for an unborn child of the affected sibling is 25%4. The trait, to the blind eye, may appear as an isolated event in smaller families with only a few children 5. The parents of the affected children could possibly be there own “kin”. The more rare the trait is in the general population, the more probable it is that inbreeding was involved. 7. What does consanguineous mean?
Consanguineous is a term to describe being related by blood or family. 8. Why is this concept especially important when discussing recessive genetic disorders? This is important when discussing these genetic disorders because consanguineous mating causes a higher risk of passing the recessive disorder. . What is it about the inheritance pattern of factor viii deficiency seen in Greg and Alga’s pedigree that point toward it not being an autocross recessive trait? The inheritance pattern of Factor VIII deficiency points more toward it being a sex- linked trait instead of autocross recessive, because it is only seen in males on the pedigree.
Resources http://education-portal. Com/academy/lesson/what-is-hemophilia —symptoms-genetic-cause-treatment. HTML 7 min tutorial on hemophilia Part 4 10. What are the characteristics of X-Inked recessive inheritance? Males are more likely to be affected than females All the affected males in a family are related by their mothers The trait is usually passed down from an affected grandfather to his daughter, who then carries the trait and passes it on to 50% of her sons. The trait is never passed directly from father to son 11.
Why does a son never inherit his father’s defective X chromosome? A son will always be lucky enough to never inherit his father’s defective X chromosome because he inherits Y from his father, not X. 12. What is required for a woman to display a sex-linked recessive trait? The woman must be homozygous for the sex-linked recessive trait in order to display it. Return to the pedigree drawn earlier for Greg and Olga; mark those persons who are carriers of the factor viii deficiency gene. 13. What is the chance that Greg carries the factor viii gene?
There is no chance that Greg carries the factor VIII gene. 14. Can he pass the gene on to his sons? His daughters? How will each be affected? He will not pass this on to his sons because they inherit the Y chromosome from him- not the X chromosome. Greg will not pass the a gene on that is affected because he doesn’t have one. Human Genetics for First Year Students: X-Inked Recessive Inheritance http://www. OIC. Du/chaises/bums/bimbos/lessons. HTML Part 5 15. What are some of the risks and benefits of genetic testing as it relates to legal (not medical) issues?