Day 6, April 14

Hello! Today we have continued working by making a video and powerpoint presentation to show our class what we have learned through this case study. Hopefully it will be as informational as these past posts.

Day 5, April 12

Hello! Today we have continued asnwering questions to further understand our case study.
The first set of questions has to do with population genetics:

1. What is the second equation?
   The second equation is p2+2pq+q2=1
   i. p2=Normal (NN)
   ii. pq=Carrier (Na)
   iii. q2=Affected (AA)
2. The incidence of cystic fibrosis in Hispanic Americans is 1/4500 while in African Americans cystic fibrosis is seen in 1 of every 15,000 births. What is the carrier frequency for each of this populations?
   1/4500 = 0.000222 = q2
   i. q = = 0.01490
   ii. p+q=1
   1. 1-0.01490=0.98510=p
   iii. 2pq=2(0.98510)(0.01490)=0.02936
   1/15000=0.000066=q2
   i. q = = 0.00812
   ii. p+q=1
   1. 1-0.00812=p
   iii. 2pq=2(0.99188)(0.00812)=0.01611
3. What is the probability of two Hispanic Americans having a child with cystic fibrosis, given that there is no history of the disease in either’s family?
   Carol is an African American woman who does not suffer from CF. Both of her parents are healthy, but her brother has cystic fibrosis. Carol is planning a family with her husband Marcus, who is also an African American but who has no history of CF in his family. What is the probability of them having a child with CF?
   The parents are carriers of CF. Thus, there is a 50% chance that Carol is a carrier too.

The next set of questions will resolve any loose ends that have been left out:

1. What are some of the risks and benefits of genetic testing as it relates to legal (not medical) issues?
   Some of the legal risks of genetic testing are loss of insurance, exclusion from employment, or other forms of discrimination.
   The problem is that genetic testing tests the LIKELIHOOD OF OCCURRENCE of diseases. For instance the presence of a cancer causing gene may indicate predisposition but does not guarantee that the person will contract the disease: How should an employer or insurer respond? The ethical, social and legal implications of these technological advances have been the subject of significant scrutiny and concern.
2. Do you think an unintended consequence of genetic testing could be that people would be less liable to seek medical care out of fear that they could later be denied life or death insurance? What laws should be used to govern the use of genetic data of this type?
   An unintended consequence of genetic testing could be that people would be less liable to seek medical care out of fear that they could later be denied life or death insurance
   To govern the use of genetic data, laws of confidentiality should be enacted. However, it is legally impossible to disable health plans or organizations from accessing such information.

Day 4, April 11

Hello! Today we began making our presentation video and continued answering more of the questions in the case study.

Now we will discuss autosomal recessive traits:

1. What are the hallmarks of an autosomal recessive trait?
   Autosomal recessive traits are characterized by males and females being having equal chances of becoming affected, the recurrence risk to the unborn sibling of an affected is individual is ¼, the trait is characteristically found in siblings not parents of affected or the offspring of the affected. Also, the parents of the children may be related depending on the rarity of the trait in the population.
2. What does consanguineous mean? Why is this concept especially important when discussing recessive genetic disorders?
   Consanguineous refers to people being of the same blood and descended from the same ancestors. This is important when discussing recessive genetic disorders because they are transmitted or inherited genetically through a person’s ancestors. The parent may therefore be related and consanguineous mating may be taking place.
3. What is it about the inheritance pattern of factor VIII deficiency seen in Greg and Olga’s pedigree that point toward it not being an autosomal recessive trait?
   Autosomal recessive traits affect both males and females equally. Factor VIII deficiency, on the contrary, only affect male, while women may be carriers of the disease. As shown in the pedigree, no females are affected.

Now that autosomal recessive traits have been discussed we proceed to the concept of X-linked recessive inheritance:

1. What are the the characteristics of X-linked recessive inheritance?
   X-linked recessive inheritance is characterized bynever being passed on from father to son, since fathers give their sons their Y chromosome. Also, all affected males in a family are related through their mothers and the trait or disease is typically passed from an affected grandfather, through his carrier daughters, to half of his grandsons.
2. Why does a son never inherit his father’s defective X chromosome?
   A son never inherits his father’s defective X chromosome because they only inherit the father’s Y chromosome which determines that the child develops as a boy.
3. What is required for a woman to display a sex-linked recessive trait?
   For a sex linked recessive trait to be displayed, the pressence of a Y chromosome is required. Since women do not have a Y chromosome they can only be carriers of the trait.
4. What is the chance that Mrs. Smith carries the gene for factor VIII deficiency? Calculate the probability that she will pass it to her offspring. Will male children be affected in a different way than female children?
   There is a 50% chance that Mrs. Smith carries the gene for factor VIII deficiency and there is a 25% chance that her female offspring is a carrier. There is a 25% cance that she will have an unnaffected female offspring and 50% chance of having an unaffected male offspring.
5. What is the chance that Mr. Smith carries the factor VIII gene? Can he pass the gene on to his sons? His daughters? How will each be affected?
   There is no chance that Mr. Smith carries the factor VIII gene; he is not affected either. Accordingly, he cannot pass the factor VIII gene to his offspring.

Day 3, April 10 2008

Today, we have begun answering the questions. Questions 1-6 discuss pedigree construction and autosomal dominant traits.
1) What would a pedigree of Mr. and Mrs. Smith families look like? Concentrate simply on family relationships and affected persons.

• Their pedigrees would show family members who posess each disease. It will also the predominance of the disease in each gender. Based on the pedigrees of both families and the information the spouses acquire from the doctor about genetic information transmition, they will see it fit or unfit to have children.

2) Do autosomal dominant disorders skip generations?

• No, because every affected individual has an affected biological parent.

3)Could Mr Smith or his mother be carriers of the gene that causes myotonic dystrophy?

• No, because autosomal dominant traits, if possessed, are always manifested.

4)Is there a possibility that Mr Smith's aunt or uncle is homozygous for the myotonic dystrophy (MD) gene?

• No, because the father of Mr Smith's aunt and uncle did not possess the dominant trait so Mr Smith's uncle and aunt are heterozygous. Their mother passed the dominant trait to them.

5)Symptoms of myotonic dystrophy sometimes don’t show up until after age fifty. What is the possibility that Mr Smith's cousin has inherited the MD gene?

• Mr. Smith's cousin has a 50% chance of having inherited the disease because one of her parents is heterozygous for the autosomal dominant trait.

6)What is the possibility that Mr and Mrs Smith's children could inherit the MD gene?

• There is no possibility of the child inheriting the disease because he has no affected parent with myotonic dystrophy. Due to the fact that this is an autosomal dominant disease, if one of the parents had inherited it, they would show symptoms. Only Mr Smith has history of this disease, but neither of his parents (who are older than 50 years old) have it.

Day 2, April 4, 2008

We constructed the pedigree for Mr. and Mrs. Smith. We then continued by looking up extra information to better understand how genetic diseases are transferred from parents to children.

• With the understanding that almost all affected individuals are heterozygotes, and that in most matings involving a person with an autosomal dominant trait the other partner will be homozygous normal, there are four hallmarks of autosomal dominant inheritance.
  Except for new mutations, which are rare in nature and extremely rare on examination pedigrees, and the complexities of incomplete penetrance to be discussed later, every affected individual has an affected biological parent. There is no skipping of generations.
  Males and females have an equally likely chance of inheriting the mutant allele and being affected. The recurrence risk of each child of an affected parent is 1/2.
  Normal siblings of affected individuals do not transmit the trait to their offspring.
  The defective product of the gene is usually a structural protein, not an enzyme. Structural proteins are usually defective when one of the allelic products is nonfunctional; enzymes usually require both allelic products to be nonfunctional to produce a mutant phenotype.
  http://www.uic.edu/classes/bms/bms655/lesson3.html

Hallmarks of x-linked recessive inheritance:

• As with any X-linked trait, the disease is never passed from father to son.
• Males are much more likely to be affected than females. If affected males cannot reproduce, only males will be affected.
• All affected males in a family are related through their mothers.
• Trait or disease is typically passed from an affected grandfather, through his carrier daughters, to half of his grandsons.
• Retrienved from: http://www.uic.edu/classes/bms/bms655/lesson7.html

Hallmarks of Autosomal Recessive Inheritance:

• Males and females are equally likely to be affected.
• On average, the recurrence risk to the unborn sibling of an affected individual is 1/4.
• The trait is characteristically found in siblings, not parents of affected or the offspring of affected.
• Parents of affected children may be related. The rarer the trait in the general population, the more likely a consanguineous mating is involved.
• The trait may appear as an isolated (sporadic) event in small sibships.
• Retrieved from:
  http://www.uic.edu/classes/bms/bms655/lesson5.html

Day 1, April 3, 2008

We began working on our case study yesterday by reading the article and looking up any terms we did not know or understand. Here is a list of the terms that we looked up.

Autosomal:

• Pertaining to a chromosome that is not a sex chromosome; relating to any one of the chromosomes save the sex chromosomes.
• Retrieved from:
  http://www.medterms.com/script/main/art.asp?articlekey=15358

Hemophilia A:

• Hemophilia A is the most common type of hemophilia. It is also known as factor VIII deficiency or classic hemophilia. It is largely an inherited disorder in which one of the proteins needed to form blood clots is missing or reduced. In about 30% of cases, there is no family history of the disorder and the condition is the result of a spontaneous gene mutation.
  
• Everyone inherits two sex chromosomes, X and Y, from his or her parents. A female inherits one X chromosome from her mother and one X chromosome from her father (XX). A male inherits one X chromosome from his mother and one Y chromosome from his father (XY). The gene that causes hemophilia is located on the X chromosome.A woman who gives birth to a child with hemophilia often has other male relatives who also have hemophilia. Sometimes, a baby will be born with hemophilia when there is no known family history. This means either that the gene has been "hidden" (that is, passed down through several generations of female carriers without affecting any male members of the family) or the change in the X chromosome is new (a "spontaneous mutation").
  There are four possible outcomes for the baby of a woman who is a carrier. These four possibilities are repeated for each and every pregnancy: 1. A girl who is not a carrier 2. A girl who is a carrier 3. A boy without hemophilia 4. A boy with hemophilia With each pregnancy, a woman who is a carrier has a 25% chance of having a son with hemophilia. Since the father's X chromosome determines the baby will be a girl, all the daughters of a man with hemophilia will be carriers. None of his sons, which is determined by the father through his Y chromosome, will have hemophilia.
• Retrieved from:
  http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=180&contentid=45&rptname=bleeding

Myotonic Dystrophy:

• Myotonic dystrophy type 1 (DM1) is an autosomal dominant, multi-system disorder that affects both smooth and skeletal muscles and may affect the central nervous system, heart, eyes, and/or endocrine systems.
• There are three types of DM1 that are distinguished by the severity of disease and age of onset. Mild DM1 is characterized by cataracts and sustained muscle contractions (myotonia). Classic DM1 is characterized by muscle weakness and wasting (atrophy), cataracts, myotonia and abnormalities in the heart’s conduction of electrical impulses. Congenital DM1 is characterized by muscle weakness (hypotonia), difficulty breathing, mental retardation and early death. DM1 is caused by an abnormality in the DMPK gene. Affected individuals have an increased number of copies of a portion of this gene called CTG. The greater the number of repeated copies of CTG, the more severe the disorder.Myotonic dystrophy type 2 (DM2), formerly called proximal myotonic myopathy (PROMM) is an autosomal dominant disorder with symptoms that are similar to DM1, but tend to be milder and more variable than DM1. DM2 is an autosomal dominant genetic disorder caused by an abnormality in the ZNF9 gene on chromosome 3q. Affected individuals have an increased number of copies of a portion of this gene.
• Retrieved from:
  http://www.webmd.com/brain/dystrophy-myotonic

Cystic Fibrosis:

• Cystic fibrosis is a disease that causes mucus in the body to become thick and sticky. This glue-like mucus builds up and causes problems in many of the body's organs, especially the lungs and the pancreas . People who have cystic fibrosis can have serious breathing problems and lung disease. They can also have problems with nutrition, digestion, growth, and development. There is no cure for cystic fibrosis and the disease generally gets worse over time. The life expectancy for people with cystic fibrosis has been steadily increasing over the past 40 years. On average, people who have cystic fibrosis live into their mid-to-late 30s, although new treatments are making it possible for some people to live into their 40s and longer.
• Cystic fibrosis is a genetic disorder. A child must inherit a specific gene from both parents to get cystic fibrosis.
• Cystic fibrosis is usually diagnosed at an early age. Although the symptoms are not the same for everyone, some common symptoms of a baby who has cystic fibrosis include:
  · A blocked small intestine at birth, which prevents the baby from passing his or her first stool
  · Very salty sweat or skin.
  · Diarrhea.
  · Not growing or gaining weight the way that other children do.
  · Breathing problems, lung infections, a cough that does not go away, and wheezing.
  Other symptoms may also develop in childhood such as:
  · Clubbing (rounding and flattening) of the fingers.
  · Rectal prolapse (when part of the rectum protrudes from the anus).
  · Growths (polyps) in the nose or sinuses.
• Retrieved from:
  http://children.webmd.com/tc/cystic-fibrosis-topic-overview

Case Study: Introduction

We are Rodolfo Diaz, Juan Guerrero, and Jorge Rivera, a group of students from Mrs. Giol's 11th grade biology class at Colegio San Ignacio who have begun working on a case study pertaining to the genetic transmission of factor VIII deficiency (Hemophillia A) and myotonic dystrophy. Mr. Smith and Mrs. Smith are a young couple who wish to have children, but they are worried about the chances of transmitting either disease to their offspring. Hence, they make a visit to a genetic counselor. Our objective in this project is to determine the chances of either disease being transmitted to their offspring.