Deck 15: Genomes and Genomics

Question 1

The gene controlling ABO blood type and the gene underlying nail-patella syndrome are said to show linkage. What does that mean in terms of their relative locations in the genome? What does it mean in terms of how the two traits are inherited with respect to each other?

Answer 1

Genes that are linked, or said to show linkage, mean that those (two or more) genes are located on the same chromosome. They are usually inherited together because they reside on the same arm of a chromosome, and chromosomes are usually inherited in whole units. Linked genes are usually inherited together, unless a recombination even occurs between the arms of two homologous chromosomes, swapping out one gene for another.

Question 2

Hemophilia and color blindness are both recessive conditions caused by genes on the X chromosome. To calculate the recombination frequency between the two genes, you draw a large number of pedigrees that include grandfathers with both hemophilia and color blindness, their daughters (who presumably have one chromosome with two normal alleles and one chromosome with two mutant alleles), and the daughters' sons. Analyzing all the pedigrees together shows that 25 grandsons have both color blindness and hemophilia, 24 have neither of the traits, 1 has color blindness only, and 1 has hemophilia only. How many centimorgans (map units) separate the hemophilia locus from the locus for color blindness?

Answer 2

A centimorgan (cM) is a genetic mapping unit, in distance, that describes the distance between two genes on a chromosome. One cM is equal to one percent of the frequency that a recombination event will occur between two genes during meiosis. The closer the genes, the smaller the distance, the less likely a recombination event will occur.
We have 2 out of 51 persons who inherited an X chromosome that underwent a recombination event between the gene loci that cause hemophilia and color blindness. We find the percentage of recombination, which is 2/51 to be 0.0392, or 3.92 percent, or 3.92 cM.

Question 3

Before the advent of recombinant DNA technology, why was it so difficult for geneticists to map human genes by using pedigrees? How did recombinant DNA technology help move things forward?

Answer 3

Before recombinant DNA (deoxyribonucleic acid) technology, many pedigrees across several generations were needed to map human genes. To increase difficulty, the genes studied would need to have an explicit phenotype. It may be relatively easy to obtain many pedigrees, but to find them for rare genetic diseases was more difficult.
Recombinant DNA technology allowed genetics to create gene maps without having to span across many generations along family lineages. The genes in question did not need to express phenotypes, because genetic markers identified genotypes. This eliminated many of the challenges that geneticist faced before the advent of recombinant DNA technology.

Question 4

In what years did the publicly funded Human Genome Project begin and end? What were the scientific goals of the HGP?

Question 5

How many nucleotides does the human genome contain?

Question 6

Which of the following best describes the process of DNA sequencing?
a. DNA is separated on a gel, and the different bands are labeled with fluorescent nucleotides and scanned with a laser.
b. A laser is used to fluorescently label the nucleotides present within the DNA, the DNA is run on a gel, and then the DNA is broken into fragments.
c. Nucleotides are scanned with a laser and incorporated into the DNA that has been separated on a gel, and then the DNA is amplified with PCR.
d. Fragments of DNA are produced in a reaction that labels them with any of four different fluorescent dyes, and the fragments then are run on a gel and scanned with a laser.
e. DNA is broken down into its constituent nucleotides, and the nucleotides are then run on a gel and purified with a laser.

Question 7

Which of the following is NOT an activity carried out in the field of bioinformatics?
a. collecting and storing DNA sequence information produced by various genome sequencing projects
b. analyzing genome sequences to determine the location of genes
c. determining the three-dimensional structure of proteins
d. comparing genomes of different species
e. none of these

Question 8

How did the sequencing strategy used by the Human Genome Project differ from that used by Celera Corporation?

Question 9

Once an organism's genome has been sequenced, how do geneticists usually go about trying to pinpoint the locations of the genes?

Question 10

What percentage of the DNA in the genome actually corresponds to genes? How much is actually protein-coding exons? What makes up the rest?

Question 11

When the human genome sequence was finally completed, scientists were surprised to discover that the genome contains far fewer genes than expected. How many genes are present in the human genome? Scientists have also found that there are many more different kinds of proteins in human cells than there are different genes in the genome. How can this be explained?

Question 12

One unexpected result of the sequencing of the human genome was the finding that mutations in a single gene can be responsible for multiple distinct disorders. For example, mutations in the RET gene can cause two different types of multiple endocrine neoplasias, familial medullary thyroid carcinoma, and Hirschsprung disease. How do you think mutations in a single gene can have such diverse effects?

Question 13

Sequence comparison studies revealed that the product of the CFTR (cystic fibrosis) gene has a strong similarity to proteins known to be involved in:
a. transcription
b. translation
c. transport of ions across the cell membrane
d. mRNA splicing
e. movement of proteins across the Golgi membrane

Question 14

You join a laboratory that studies a rare genetic disorder that causes affected individuals to have unusually fast-growing, bright green hair. You are joining the lab at a fortuitous moment, as the gene causing the disorder has just been cloned. Despite this breakthrough, however, it is still unclear what the function of the gene is, and the lab director asks you for suggestions about how to go about trying to determine this. What do you recommend?

Question 15

How does proteomics differ from genomics? What kinds of information can proteomics provide that is not available from genomics studies?

Question 16

How did the Human Genome Project attempt to deal with the social and ethical issues that were bound to arise from the sequencing of the human genome?

Question 17

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
Do James and Sally have any guarantees that the tests and recommendations are scientifically valid?

Question 18

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
Do you think that companies should be allowed to market such tests directly to the public, or do you believe that only a physician should be able to order them?

Question 19

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
What kinds of regulations, if any, should be in place to ensure that the results of these tests are not abused?

Question 20

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
Do you think parents should be able to order such a test for their children? What if the test indicates that a child is at risk for a disease for which there is no known cure?

Question 21

Both the Human Genome Project (HGP) and Celera's genome sequencing project were faced with an interesting dilemma: Whose DNA should be sequenced? Whose genome should serve as a "representative" human genome? The HGP and Celera answered the question in different ways. The HGP started with a collection of DNA samples from a large number of individuals and then randomly selected a small number of samples that were used for sequencing. Celera, in contrast, used a mixture of DNA samples from several individuals of diverse ethnicity (including, as was later revealed, the DNA of Celera's founder, Craig Venter). In both cases, because only a handful `of genomes were used in the sequencing, the final sequences represented only a small fraction of the total variation present in humanity.
In 1991, as the genome project got under way, a group of anthropologists and geneticists proposed carrying out an ambitious project to address this issue-namely, to study the genetic variation of all human populations. The Human Genome Diversity Project, as it came to be called, proposed to obtain blood samples from a wide variety of peoples throughout the world and to sequence their genomes in conjunction with the official human genome project. According to the organizers of the project, the information obtained in the project would shed light on the history of different human populations, illuminate the biological relationships between populations, and probably be useful for understanding the causes and genetic features of various diseases.
Although the proposal won some initial support, it soon ran into several major-and ultimately insurmountable-obstacles. Certain scientists questioned its scientific rationale, casting doubt on whether the project would yield important information about human history and disease. But the greatest difficulties came from many of the indigenous populations that the organizers hoped would be participating in the project. The subjects viewed the project suspiciously, raising questions about its true purpose and value: Who would "own" the genetic information that was generated during the project? Would it be patented? Who would benefit from drugs or other products developed by using the information? What other purposes could the genetic information be used for (either good or bad)? Wouldn't the millions of dollars that would be spent on the project be better used trying to help indigenous populations directly?
Despite the attempts of project organizers to address those questions, the critics never relented, and the project was essentially abandoned in the late 1990s. Since then, other alternative approaches have been initiated to try to address issues related to human genetic diversity, such as the HapMap project that officially got under way in 2002.
Is it ethical for scientists from developed countries to involve indigenous populations from less developed parts of the world in their research studies, or should they limit their studies to populations living in their own countries?

Question 22

Both the Human Genome Project (HGP) and Celera's genome sequencing project were faced with an interesting dilemma: Whose DNA should be sequenced? Whose genome should serve as a "representative" human genome? The HGP and Celera answered the question in different ways. The HGP started with a collection of DNA samples from a large number of individuals and then randomly selected a small number of samples that were used for sequencing. Celera, in contrast, used a mixture of DNA samples from several individuals of diverse ethnicity (including, as was later revealed, the DNA of Celera's founder, Craig Venter). In both cases, because only a handful `of genomes were used in the sequencing, the final sequences represented only a small fraction of the total variation present in humanity.
In 1991, as the genome project got under way, a group of anthropologists and geneticists proposed carrying out an ambitious project to address this issue-namely, to study the genetic variation of all human populations. The Human Genome Diversity Project, as it came to be called, proposed to obtain blood samples from a wide variety of peoples throughout the world and to sequence their genomes in conjunction with the official human genome project. According to the organizers of the project, the information obtained in the project would shed light on the history of different human populations, illuminate the biological relationships between populations, and probably be useful for understanding the causes and genetic features of various diseases.
Although the proposal won some initial support, it soon ran into several major-and ultimately insurmountable-obstacles. Certain scientists questioned its scientific rationale, casting doubt on whether the project would yield important information about human history and disease. But the greatest difficulties came from many of the indigenous populations that the organizers hoped would be participating in the project. The subjects viewed the project suspiciously, raising questions about its true purpose and value: Who would "own" the genetic information that was generated during the project? Would it be patented? Who would benefit from drugs or other products developed by using the information? What other purposes could the genetic information be used for (either good or bad)? Wouldn't the millions of dollars that would be spent on the project be better used trying to help indigenous populations directly?
Despite the attempts of project organizers to address those questions, the critics never relented, and the project was essentially abandoned in the late 1990s. Since then, other alternative approaches have been initiated to try to address issues related to human genetic diversity, such as the HapMap project that officially got under way in 2002.
Do you think such a project would be likely to help indigenous populations? Do you think the objections to the project were reasonable?

Question 23

Both the Human Genome Project (HGP) and Celera's genome sequencing project were faced with an interesting dilemma: Whose DNA should be sequenced? Whose genome should serve as a "representative" human genome? The HGP and Celera answered the question in different ways. The HGP started with a collection of DNA samples from a large number of individuals and then randomly selected a small number of samples that were used for sequencing. Celera, in contrast, used a mixture of DNA samples from several individuals of diverse ethnicity (including, as was later revealed, the DNA of Celera's founder, Craig Venter). In both cases, because only a handful `of genomes were used in the sequencing, the final sequences represented only a small fraction of the total variation present in humanity.
In 1991, as the genome project got under way, a group of anthropologists and geneticists proposed carrying out an ambitious project to address this issue-namely, to study the genetic variation of all human populations. The Human Genome Diversity Project, as it came to be called, proposed to obtain blood samples from a wide variety of peoples throughout the world and to sequence their genomes in conjunction with the official human genome project. According to the organizers of the project, the information obtained in the project would shed light on the history of different human populations, illuminate the biological relationships between populations, and probably be useful for understanding the causes and genetic features of various diseases.
Although the proposal won some initial support, it soon ran into several major-and ultimately insurmountable-obstacles. Certain scientists questioned its scientific rationale, casting doubt on whether the project would yield important information about human history and disease. But the greatest difficulties came from many of the indigenous populations that the organizers hoped would be participating in the project. The subjects viewed the project suspiciously, raising questions about its true purpose and value: Who would "own" the genetic information that was generated during the project? Would it be patented? Who would benefit from drugs or other products developed by using the information? What other purposes could the genetic information be used for (either good or bad)? Wouldn't the millions of dollars that would be spent on the project be better used trying to help indigenous populations directly?
Despite the attempts of project organizers to address those questions, the critics never relented, and the project was essentially abandoned in the late 1990s. Since then, other alternative approaches have been initiated to try to address issues related to human genetic diversity, such as the HapMap project that officially got under way in 2002.
If a scientist makes a medically important discovery using DNA obtained from an indigenous group, should the discovery be patentable? How should any benefits arising from such a discovery be shared?