3.Treatments: Surgery, Radiation, Chemotherapy, Immunological Control and Genetic Control

Problem Set #3

1.Unlimited growth of cells that robs the host of nutrients. Leukemia – white blood cell cancers originating in the bone marrow. Sarcomas – solid tumors from mesoderm tissue. Lymphomas – abnormally large numbers of lymphocytes originating in the lymph nodes or spleen. Carcinomas – solid tumors from epithelial tissue. 2.Environmental causes: Carcinogens such as components of cigarette smoke, asbestos, X-rays, and viruses. Genetic causes: Single-gene, polygenic inheritance, chromosome aberrations, and somatic mutation. 3.Treatments: Surgery, radiation, chemotherapy, immunological control and genetic control. 4. a)Schizophrenia: Most common mental disorder; onset in early adulthood; characteristic sweat variants. b)Manic Depression (Bipolar disorder): Alternate between euphoric, violent behavior and deep states of depression. c)Epilepsies (Seizures): Due in part to heredity; high fevers in childhood. d)Alcoholism: Brain degeneration; possible genetic involvement; alcoholic dehydrogenase; aldehyde dehydrogenase variants. e)Parkinson Disease: Loss of body control; do not metabolize dopamine normally. f)Huntington Disease: Autosomal dominant; degeneration of the brain; onset typically 40-45 years of age. 5.Trisomy 21, Trisomy 18, Trisomy 13, XXY, and XYY. 6.Genetic involvement: Simple Mendelian inheritance, polygenic heredity, and chromosome aberrations. Environmental causes: Prenatal, peri-natal, and post- natal care. 7.Better nutrition today, more people live to “old age,” lifestyle changes, exposure to more mutagens and carcinogens today, use of antibiotics, immunizations, and other medical advances. 8.Euploid: Whole sets of chromosomes, e.g., n = haploid or monoploid, 2n = diploid, 3n = triploid, 4n = tetraploid. Aneuploid: Cells with one or more chromosome(s) extra or missing, e.g., trisomy 21 or 45, XO Turner Syndrome. 9.Gene (allele) frequencies and genotype frequencies remain the same for successive generations if the following conditions are met: 1. The population is infinitely large. 2. Mating is random. 3. There is no selection. 4. There is no mutation. 5. There is no migration. 10.To help their clients comprehend the medical facts involved, appreciate the way heredity contributes to the disorder, understand the recurrence risks, choose the course of action which seems appropriate to them in view of their risk, the background, their religious perspectives, etc. 11.Evidence against A.D.: Expect at least one of the parents of III-2 and III-4 to be affected; A.R.: No evidence against; X.D.: All daughters of I-2 would have to be affected; Mother of II-4 would have to be affected; Mother of III-4 would have to be affected; One (or both) parent(s) of III-2 would have to be affected; X.R.: Expect father of III-2 to be affected; Expect all sons of II-6 to be affected; Y.: All sons of I-1 would have to be affected; Father of III-4 would have to be affected; No females could be affected.

Test #3 Keys April 23, 1999 1a. RFLP Analysis/DNA Testing/DNA "Fingerprinting" - A means of cutting DNA into pieces, separating them and observing the # and sizes of them. Since DNA samples (cells) from different individuals are unique, this method enables absolute identification. Useful in forensics, paternity testing, accidents, military, adoption, immigration, etc. 1b. Polygenic Inheritance - Characteristics due to many genes (and often many environmental factors, too), e.g., height, weight, I.Q., etc. 1c. MZ:DZ Concordance Values of 100:37 - Would indicate that the characteristic is determined entirely by genes, e.g., ABO blood type or Freckles. 1d. RhoGAM - Infection of anti-Rh antibodies into Rh- mother after she has delivered Rh+ baby. Purpose is to destroy any Rh+ cells in mother’s system that may have been transmitted from baby. This will keep mother from making her own anti-Rh antibodies and eliminate any risk of Rh incompatibilities in subsequent Rh+ fetus. 1e. Heritability for Weight = 0.78 - Means that ~ 75-80% of the factors influencing adult weight are genetic, the remaining ~ 20-25% environmental. 1f. I.Q. Correlations of 0.16 for Adopted Children and their Adopted Parents and 0.36 for Adopted Children and their Biological Parents - Adopted kids are (for I.Q.) only a little bit like their environmental parents (low correlation value), but a good bit more like their genetic parents (higher correlation value). Genetics appears to be the more important factor.

2a. T 2b. F - DZ (or MZ is not increasing) 2c. F - retina (eye) cancer 2d. F - much more so than by

3a. Yes Yes 3b. No Yes

4a. B 4b. D 4c. D 4d. A 4e. C 4f. B

5a. B 5b. A 5c. D 5d. B 5e. C 5f. C (or D)

6a. A 6b. B 6c. C 6d. D

7a. X-linked recessive - No, Since II-3 is affected, her son (III-2) would have to be as well. 7b. X-linked dominant - No, For III-1 to be affected, his mother (II-1) would also have to be affected. 7c. Y-linked trait - No, II-3, a female, is affected . . . females don’t have a Y. Also, there are two father-son discrepancies: II-2 is not affected, yet his father (I-2) and son (III-1) are. II-4 is affected, but his son (III-1) is not. (Either answer is sufficient.) 7d. autosomal dominant - No, For III-1 to be affected, one of his parents (II-1 or II-2) would also have to be. 7e. autosomal recessive - No, Since II-3 and II-4 are both affected, their children would also have to be; III-2 is not.

8a. 7 x 6 = 42 8b. 1 x 6 = 6 - N1N1N2N2N3N3 8c. 18 to 36

9a-c. Up to 9 points (3 for each "argument") for well thought-out, documented, explained, etc. reasons for the Gillen visit being a semester highlight.

10. 5 points on Class Attendance Record

11.Signature

November 24, 1999 1a. Nondirective Counseling - The approach genetic counselors use, where diagnoses are made, tests are done, explanations given, recurrence risks calculated, prognoses provided, support offered, etc. without ever telling anyone what to do. GC'' assist counselees in searching a decision, but don't push them one way or another. 1b. Hyperplasia - The proliferation without control characteristic of cancer. Cancer cells continue to move through the cell cycle without the normal checks/check points. Although slowly, these unchecked cell divisions eventually produce large #s of cells. 1c. Lawrence Gillen - Brother of Rachel. Rachel has Down Syndrome. Other family members are also impacted +/- by Down Syndrome. Brother Lawrence shared his perspective with us in GN 301. 1d. Mental Illness, NOT Mental Retardation - Any of many central nervous system (CNS) problems which result in mental instability or diminished function. Examples include: schizophrenia, bipolar disorder, Alzheimer disease and many more. Most are multifactorial, i.e., have many genes and many environmental factors contributing to their cause. 1e. Teratogen - Any agent which causes a birth defect. Example: Thalidomide (an anti-nauseant) causes limb malformation when exposure is at critical stages of prenatal development. Teratogens are not necessarily mutagens, e.g., thalidomide is not. . .i.e., it does not alter the DNA.

2a. B 2b. D 2c. B 2d. A

3a. F - Fetal Alcohol Syndrome 3b. T 3c. T 3d. F - fraternal than identical 3e. F - slower 3f. T

4a. A 4b. A 4c. C 4d. C

5a. 100%G______100%E Cystic Fibrosis Heart Disease 5b1. Heart Disease - due to a mix (say, 50:50) of genetic and environmental factors; multifactorial; runs in families; environment, stress, diet, etc. make a difference; polygenic. 5b2. Cystic Fibrosis - Mendelian inheritance; autosomal recessive inheritance (gene/locus on chromosome 7) is responsible for causing Cystic Fibrosis . . . i.e., a 100% genetic cause; environmental factors, e.g., improved treatment is enabling longer and higher quality lives, thus environment is somewhat important, too.

6a. D 6b. E 6c. A 6d. C

7. That both Genetics and Environment play a significant role. This is based on the fact that I.Q. correlations between an adopted individual and his biological family (Parent = 0.36; sibling = 0.38) are positive, and so are the correlation values between the adopted child and their environmental family members (0.16 and 0.30).

8a. Yes, it could be. 8b. No - For III-2 to be affected, her father (II-2) would also have to be. He is not. 8c. Yes, it could be. 8d. No. Two Females (II-2 and III-2) are affected. Females do not have a Y chromosome. There is also a father-son discrepancy between II-1 and III-1. (Either explanation is sufficient, both are not needed.) 8e. No - For II-3 to be affected, his mother I-1 would have to be. She is not.

9. Up to 10 points for exceptionally thorough, well documented, clearly communicated and convincing elaboration of why the one they chose was the more important GN 301 experience.

10a. A 10b. C 10c. D 10d. B 10e. A

11. Up to 5 points on Class Attendance Record.

12. Signature

April 28, 2000 1a. Nondirective Counseling – The approach/method that genetic counselors use. Information about tests available, treatment options, probabilities of occurrence, prognoses, etc. are given to counselees without telling them what course of action to take. 1b. Metastasis – The spreading nature of cancer . . . from site of origin to other tissues and organs. Movement is via the circulatory and lymphatic systems. 1c. Sarcoma – A relatively rare (~2% of all cancers) class of cancers, involving bone, muscle, cartilage, fat tissue, often difficult to treat. 1d. Heritability (h2) = 0.78 for Weight – Means that ~78% of the factors that influence weight are genetic ones; the remaining ~ 22% of weight is determined by environment. 1e. Genetics and Mental Retardation – Of known causes of mental retardation, ~ 2/3 are due to genetics. Categorically, some cases are due to Mendelian (single gene) genotypes, others due to chromosome abnormalities, and some due to polygenic (multifactorial) factors.

2a. E, A 2b. A 2c. C 2d. D 2e. D

3a. C 3b. A 3c. C 3d. A 3e. B 3f. C

4a. Adoptive Biological “Parent” 0.16 0.36 “Sibling” 0.30 0.38

4b. That both G and E are influencing I.Q. test results, i.e., G because adopted kids’ I.Q.s are positively correlated with their genetic parents (0.36) and genetic siblings (0.38). E because the same adopted kids’ I.Q.s correlate positively with their adopted “parents” (0.16) and adopted “siblings” (0.30).

5. Up to 10 points for a well thought-out, well documented, well communicated response, which puts their experience with Cam Brasington or the Gillens in a “Genetics in Human Affairs” context. 6a. X-linked dominant – No; (Lots of exceptions; any one will suffice.) All daughters and mothers of affected males must all be affected. None of them are. 6b. X-linked recessive – Yes 6c. Y-linked trait – No; II-1 and III-2 are not alike. Can’t have a father-son discrepancy. 6d. autosomal recessive – Yes 6e. autosomal dominant – No; Neither of the parents of III-2 are affected. At least one of them (II-1 or II-2) must be.

7a. B 7b. A 7c. D 7d. D

8a. F; lower 8b. T 8c. F; more slowly 8d. F; fraternal than identical 8e. F; not known to be inherited, both genetic and environmental 8f. F; are not

9a-b. Up to 4 points for each of two different, well explained responses that speak to different examples/conditions/situations from the video.

9.Up to 5 points for Class Attendance Record.

10.Signature

December 1, 2000 1. a. MZ:DZ Concordance values of 75:20 for characteristic A – This characteristic would be largely genetic due to the nearly 4-fold higher concordance in MZ twins than in DZ twins. Not completely genetic though since the MZ value is not 100. b. RhoGAM – Injection of Anti-Rh antibody. Used to destroy Rh+ cells from fetus which may have entered Rh- mother during delivery. Prevents incompatibility problems in subsequent Rh+ pregnancies. c. Metastasis – The spreading nature of cancer cells from site of origin to other locations in the body. This aspect/feature of many cancers is, like others, due to genes. d. Guevodoces – A sex developmental abnormality. XY individuals with abdominally located testes appear at birth to be female . . . a result of failure to activate testosterone. At puberty, they masculinize . . . penis forms. e. Type O Blood – One of 4 ABO blood types. Neither A nor B antigens are produced. OO genotype. Often called the “Universal Donor”.

2a. D 2b. D, A 2c. C 2d. A 2e. C

3a. D 3b. C 3c. D 3d. A 3e. D

4a. D 4b. B 4c. D 4d. C

5a. T 5b. F; are not mentally retarded 5c. F; DZ instead of MZ 5d. F; lower 5e. F; genetic or a mix of genetic and environmental 5f. F; slower than

6a. Y-linked trait – Yes 6b. X-linked dominant – No; III-1 and III-3 are affected males without affected mothers which is not possible. Also, III-2 is not affected, yet her father is, which isn’t possible. (Either answer is sufficient). 6c. Autosomal recessive – Yes 6d. X-linked recessive – Yes 6e. Autosomal dominant – Yes

7a. influenced or conditioned 7b. B’B’ 7c. BB 7d. O 7e. 1 or 100%

8. Adoptive Biological “Parent” 0.16 0.36 “Sibling” 0.30 0.38

That both genetics and environment contribute to I.Q. The evidence supporting genetics: the positive correlations (0.36 and 0.38) for adopted kids and their biological parents and biological siblings respectively. The evidence for environment: the positive correlations (0.16 and 0.30) for the adopted child and their adopted “parents” and “siblings” respectively. 9a. G’G’ G’G’ G’G’ G’G’ (homozygous recessive for all 4 loci) 9b. G’G G’G G’G G’G 9c. ½ x ½ x ½ x ½ = 1/16 9d. G’1G1 G’2G’2 G3G3 G’4G4 1) 1 (smallest) 7 (largest) 2) 0 (No chance)

10.Up to 4 points for well thought-out explanation that discusses the immunogenetic principles involved.

11.Up to 5 points for Class Attendance Record

12.Signature

April 27, 2001 1. a. Nondirective Counseling – The approach used by genetic counselors with their counselees, where information, perspective, pros and cons, support, understanding, and empathy are provided without telling/indicating/suggesting what, if any, course of action to take with regard to their genetic situation. b. Concordance Values of 77:11 for Trait A – Trait A would be substantially genetic in that MZ twins are 7 times more often alike than are DZ twins. Trait A is not totally genetic, however, since MZ twins are not alike 100% of the time. c. Phenocopy – A characteristic caused by some environmental exposure which resembles a gene caused one. If it were gene caused it would be a phenotype. Thalidomide exposure prenatally can cause limb malformations, for example. d. Bipolar Disorder – A mental illness characterized by severe mood swings: high energy/invincibility to deep depression/despair. Also (formerly) called Manic Depression. MZ:DZ concordance values (high:low) indicate genetics is a major player. e. Carcinoma – 85% of cancers are of this type/category. Includes skin cancers, colon cancers, lung cancers, etc. Cancers of “body covering”/epithelial/epidermal . . . in origin types of tissues.

2a. C 2b. D, A 2c. C 2d E 2e. C

3a. T 3b. F; slower than 3c. T 3d. T 3e. T 3f. T 3g. F; lower 3h. F; genetic (or a mix of genetic and environmental factors)

4a. No; He or she would have (3 x 2) + (3 x 5) = 21 “units” 4b. 6 x 5 = 30 4c. (5 x 5) + 2 = 27 C’1C’1 C’2C’2 C’3C3; Yes

5a. X-linked recessive – Yes 5b. autosomal dominant – Yes 5c. Y-linked trait – No; Father-son discrepancy between I-2 and II-3. 5d. autosomal recessive – Yes 5e. X-linked dominant – No; Daughters and mothers of affected males must be affected, thus II-1 and III-1 should be affected, but they are not.

6.Up to 10 points for exceptionally well communicated, well documented responses. (These are not “free” points. Responses need to have substance.)

7a. B 7b. A 7c. B 7d. D

8a-b. Up to 4 points for each of two different, well thought-out and well communicated examples/conditions/situations from the video.

9. Adoptive Biological “Parent” 0.16 0.36 “Sibling” 0.30 0.38 a.I.Q. correlations are positive for adopted kids and their genetic/biological 1st degree relatives (0.36 and 0.38) even though they haven’t lived with them. No doubt the reason for the positive correlation is that they share genes. b.I.Q. correlations are positive for adopted kids and their adoptive “family” members (0.16 and 0.30), indicating that shared environment matters, too. Since these individuals have no genes in common, shared environment must be the explanation for the positive I.Q. correlation values.

10.Up to 5 points extra credit for Class Attendance Record.

11. Signature

November 30, 2001 1.

a. Genetics and Intelligence - Several different types of studies indicate that Genetics strongly influences Intelligence : Twin studies, comparison of IQs of adopted children and their genetic "family" members, population studies, etc. Heritability : h2 = 0.6 +/- 0.2. Environment is important too, but genes are at least (if not more so) as influential./li> b. Hyperplasia - Characteristic of cancer involving the uncontrolled proliferation of cells through unchecked cell divisions (mitosis). Cell cycling is not fast. Instead, it is without genetic control. c. Oncogenes vs. Tumor Suppressor Genes - Oncogenes act as "accelerators" of the cell cycle. Tumor Suppressor Genes act as "brakes" for the cell cycle. If mutations (greater than or equal to 12) occur in one or the other of these two gene families, cells lose control or regulation of their movement through the cell cycle, i.e., cancer. d. Siamese Twins - Siamese twins, such as Chang and Eng. Monozygotic (Identical twins) that failed to come completely apart. Siamese twinning is not inherited. e. Antibodies - Gene products made in response to the recognition of the presence of foreign antigens. Significant components of our immunogenetic system . . . our inherited (and varied) ability to protect ourselves.

a. T b. F, Rh c. F, less d. T e. T f. F, Heart Disease g. F, DZ (Fraternal) twinning runs in families, but MZ (identical) twinning does not h. T

a. B b. C c. A d. A

a. D b. C c. B d. D 5.

a. C b. E c. A d. D e. A

a. No *Since II-2 is affected, III-2 would have to be, but he is not. b. No *II-2 is an affected female, and females don't have a Y chromosome. *II-3 and III-4 represent a father-son discrepancy. They must be alike but are not. *I-2 and II-3 represent a father-son discrepancy. They must be alike but are not. *II-1 and III-2 represent a father-son discrepancy. They must be alike but are not. c. No *For III-4 to be affected, one (or both) of his parents must be affected, but neither is. d. No *Since III-4 is affected, his mother (II-4) would also have to be affected, but she isn't. e. No *Since II-1 and II-2 are affected, all their kids would have to be. III-2 is not.

a. No b. 24 = 16 c. No d. Any which require crossing over, e.g., ABCD or abcd . . . any which have "BC" or "bc" along with either kind of "A" and either kind of "D".

8. Up to 4 points for each of two different examples, explanations from the Conquering Cancer video.

9. Up to 5 points for a good description including the immunogenetic principles involved.

a. DNA from two or more sources is cut into pieces (using an enzyme). If the DNA samples are from different individuals there will be a different number and different sizes of pieces. When the DNA is separated, the band (DNA) of different individuals can be distinguished . . . a powerful means of determining identity. b. Any one of the following (or acceptable other) with a brief explanation. *Forensics *Paternity Testing *Military; MIAs *Accident Victim ID *Adopted Children *Immigration Identification

11. Signature

April 26, 2002 1.

a. Huntington Disease - Mental illness involving progressive brain degeneration, usually beginning in mid/late adult life (approximately around age 40+/-). Inherited as a simple autosomal dominant (excessive repeats of CAG codon in chromosome #4). b. Linked Genes - Two genes/loci on the same chromosome pair, e.g., "A" and "B". The "A" and "B" arrangement tends to stay together in gamete formation, although crossing over can shuffle them. c. Teratogen - An agent that causes a birth defect, e.g., thalidomide exposure early in prenatal development can cause limb malformations in the embryo/fetus. d. Metastasis - The spreading nature of cancer . . . from site of origin to elsewhere in the body via the circulatory or lymphatic systems. Frequently the new site is more problematic than the original one. e. Heritability (h2) for IQ = 0.6 +/- 0.2 - This indicates that approximately 60% +/- 20% of all the variation in IQ scores is attributable to genetics . . . the remaining approximately 40% to environment.

a. F, Cancer b. T c. F, known to have somewhat of a genetic bias d. T e. T f. F, lower g. T h. T

a. Based on the biological correlation: Since there is a similarity that is substantially positive (in the correlation value) for IQ between adopted kids and those with whom they share 1/2 their DNA, it is reasonable to conclude that the DNA in common is responsible. b. Based on the adoptive correlation: Similarly, there is a positive (albeit weakly so) correlation in IQ scores between adopted kids and those with whom they live. It is reasonable to conclude that the common environment is the explanation.

a. E b. B c. A d. C

a. A b. E c. D d. C e. A

a. No *Since III-3 is affected, his mother II-4 would have to be affected but she isn't. b. No *Since III-3 is affected, one or both of his parents would have to be affected, but neither is. c. Yes d. No *Since III-2 is affected, her father (II-1) would have to be affected, but he isn't. e. No *Two females are affected, but they don't have a Y. *Father-son discrepancy . . . I-2, II-3, and III-3 should all have the same phenotype but don't.

a. Yes b. 5 x 6 = 30 units (which is greater than 26) c. 2 x 6 = 12 d. 7 x 3 = 21 e. C1'C1 C2'C2 C3'C3, No

8. Up to 4 points for a good description including the immunogenetic principles involved.

a. T b. F, high c. F, are discouraged from sharing d. F, negative e. F, Some f. F, give up their baby for adoption because they felt it would not be well accepted in their society when they returned to Egypt. g. T h. T

10. Up to 3 points for any one case that Cam Brasington spoke about that is described in some detail.

a. B b. A c. D d. B e. D

12. Signature