Answers to Review Questions s2

Chapter Twenty-Two

ANSWERS TO REVIEW QUESTIONS

1. The exome is the portion of the genome composed of exons and encodes proteins. A genome is all the genetic information in a cell, characteristic of the species; the exome is a small percent of the genome.

2. Helped assign genes to specific chromosomes.

3. Cytogenetic maps associate genes with chromosomes or chromosome bands. Linkage maps use recombination frequencies to order genes by relative distances. Physical maps use overlapping DNA sequences to give the physical location of genes along chromosomes. Sequence maps depict the linear order of nucleotides. Newer maps include gene expression, SNPs, methylation, and gene interactions.

4. Researchers identified markers associated with the disease causing genes. Chromosome walking created a map from overlapping DNA sequences that included genes of interest.

5. Concerns over cost, allocation of scarce research funding, potential benefits, and issues of privacy and genetic discrimination.

6. Copy number variants are only counted once in sequencing because they do not change the sequence.

7. The sequencing of the human genome did not reveal what genes actually do. Sequencing the initial genome did not reveal how people vary.

8. Pieces must be overlapped to derive the sequence, so several genome copies must be used. The more copies, the fewer parts of the sequence are missed.

9. A common variant has not been selected against. Its persistence argues for its safety.

10. The microbiome affects human gene expression.

11. Conserved DNA sequences represent genes selectively retained through evolution, suggesting that they have a vital function. Genes that are highly conserved in organisms past a point of increased complexity reveal great changes in life, such as the minimum gene set required for life, fundamental distinctions among the three domains of life, the basic blueprint of an animal and what makes humans unique.

12. An inversion does not alter the sequence so would not show up in exome sequencing. It might show up in genome sequencing if it is included in different fragments.

13. Limitations: exome and genome sequencing do not provide information about the effects of the environment, gene expression interactions, or repeats.

14. Does benefit outweigh risk? Does it work? Will it help people who can’t use existing products?

15. Types of information learned from knowing genome sequences: what recessive genes are carried; mutations that will manifest in the future; which drugs are likely to be effective with minimal side effects.

ANSWERS TO APPLIED QUESTIONS

1. Genetic and genomic information can help a health care provider to diagnose disease. For example, a person may have anemia for many reasons, inherited and acquired (such as from a poor diet). Knowing the genetic cause can indicate the most appropriate treatment, but the symptoms of anemia might have been what led a person to contact a health care provider, and be tested to detect the anemia. Then genetic testing could have provided much more specific information. The other way around, diagnosing based on a genetic or genomic test, can lead to a false positive due to incomplete penetrance. Genetic tests are less helpful and precise for multifactorial conditions because many causative factors each contribute to a different degree.

2. A standard diagnostic test is less precise than a DNA-based test. A DNA test provides information on the mechanism of the illness.

3. An advantage is cost savings. Disadvantages are missing diagnoses and stereotyping people, which could be construed as discrimination.

4. Opinion

5. Genome sequencing can reveal de novo cases—genetic disease that arises from spontaneous mutation and therefore is not in the family.

6. A child born with symptoms that no one else in the family has, and that does not match a known syndrome.

ANSWERS TO WEB ACTIVITIES

1. The first phase of eMERGE associated variants (such as SNPs) to clinical measurements and other phenotypes in many people. The second phase is applying that information to refine genetic risk assessment, prevention, diagnosis, and choice of treatment. Issues such as privacy and accessibility are also being examined.

2. Individual hu43860C at the Personal Genome Project is a 246-pound white male who stands 6 feet, 5 inches tall. He has chest pain, high triglycerides, narcolepsy, and squamous cell carcinoma. He takes Flonase and a statin drug. His genome sequence indicates that he is a heterozygote for a form of Charcot-Marie-Tooth disease, alpha-1-anti-trypsin deficiency (inherited emphysema), Bardet-Biedl syndrome, and right ventricular cardiomyopathy. He will likely develop age-related macular degeneration. If he were female, he would be at slightly elevated risk of having a child with Down syndrome.

3. Genome analysis of thyroid tumors from 500 patients revealed gene variants associated with more serious disease that is likely to spread.

4. Affordability of exome and genome sequencing.

5. Identification of gene variants in people with mitochondrial disease, autism, epilepsy, intellectual disability, metabolic conditions to determine which drugs are likely to work and offer suggestions about diet.

ANSWERS TO CASE STUDIES AND RESEARCH RESULTS

1. (a) AAGCTAAT and TAGCTACT (b) 4 and 8 (c) 1 (d) 1 due to variability (e) Fish #3

2. Such an experiment might be considered unethical and would be difficult to control, but compare a group of individuals who base their lifestyle choices on knowledge of their genomes (theirs or their health care providers) to a matched group who do not have genome information, and compare their long-term health.

3. a. phenotype b. a heterozygote for either of the mutations that his parents have, or wild-type c. 1 in 4 d. dominant e. the mother is a manifesting heterozygote