Information

17.3: Heart - Biology


Lub Dub

Lub dub, lub dub, lub dub... That’s how the sound of a beating heart is typically described. In a normal, healthy heart, those are the only two sounds that should be audible when listening to the heart through a stethoscope. If a physician assistant hears something different from the normal lub dub sounds, it’s a sign of a possible heart abnormality. What causes the heart to produce the characteristic lub dub sounds? Read on to find out.

The heart is a muscular organ behind the sternum (breastbone), slightly to the left of the center of the chest. The function of the heart is to pump blood through the blood vessels of the cardiovascular system. The continuous flow of blood through the system is necessary to provide all the cells of the body with oxygen and nutrients and to remove their metabolic wastes.

Structure of the Heart

The heart has a thick muscular wall that consists of several layers of tissue. Internally, the heart is divided into four chambers through which blood flows. Blood flows in just one direction through the chambers due to heart valves.

Heart Wall

As shown in Figure (PageIndex{2}), the wall of the heart is made up of three layers, called the endocardium, myocardium, and pericardium.

  • The endocardium is the innermost layer of the heart wall. It is made up primarily of simple epithelial cells. It covers the heart chambers and valves. A thin layer of connective tissue joins the endocardium to the myocardium.
  • The myocardium is the middle and thickest layer of the heart wall. It consists of cardiac muscle surrounded by a framework of collagen. There are two types of cardiac muscle cells in the myocardium: pacemaker cells, which have the ability to contract easily; and pacemaker cells, which conduct electrical impulses that cause the cardiomyocytes to contract. About 99 percent of cardiac muscle cells are cardiomyocytes, and the remaining 1 percent are pacemaker cells. The myocardium is supplied with blood vessels and nerve fibers via the pericardium.
  • The epicardium is the third layer which is a part of the pericardium, a protective sac that encloses and protects the heart. The pericardium consists of two membranes (visceral pericardium called epicardium and parietal pericardium), between which there is a fluid-filled cavity. The fluid helps to cushion the heart and also lubricates its outer surface.

Heart Chambers

As shown in Figure (PageIndex{3}), the four chambers of the heart include two upper chambers called atria (singular, atrium) and two lower chambers called ventricles. The atria are also referred to as receiving chambers because blood coming into the heart first enters these two chambers. The right atrium receives blood from the upper and lower body through the superior vena cava and inferior vena cava, respectively; and the left atrium receives blood from the lungs through the pulmonary veins. The ventricles are also referred to as discharging chambers because the blood leaving the heart passes out through these two chambers. The right ventricle discharges blood to the lungs through the pulmonary artery, and the left ventricle discharges blood to the rest of the body through the aorta. The four chambers are separated from each other by dense connective tissue consisting mainly of collagen.

Heart Valves

Figure (PageIndex{3}) also shows the location of the four valves of the heart. The heart valves allow blood to flow from the atria to the ventricles and from the ventricles to the pulmonary artery and aorta. The valves are constructed in such a way that blood can flow through them in only one direction, thus preventing the backflow of blood. The four valves are the:

  1. tricuspid valve, which allows blood to flow from the right atrium to the right ventricle.
  2. the mitral valve, which allows blood to flow from the left atrium to the left ventricle.
  3. pulmonary valve, which allows blood to flow from the right ventricle to the pulmonary artery.
  4. the aortic valve, which allows blood to flow from the left ventricle to the aorta.

The tricuspid and mitral valves are also called atrioventricular (or AV) valves because they are found between the atrium and the ventricle. The pulmonary and aortic valves are also called semilunar valves because they are shaped like half-moons.

Coronary Circulation

The cardiomyocytes of the muscular walls of the heart are very active cells because they are responsible for the constant beating of the heart. These cells need a continuous supply of oxygen and nutrients. The carbon dioxide and waste products they produce also must be continuously removed. The blood vessels that carry blood to and from the heart muscle cells make up the coronary circulation. Note that the blood vessels of the coronary circulation supply heart tissues with blood and are different from the blood vessels that carry blood to and from the chambers of the heart as part of the general circulation. Coronary arteries supply oxygen-rich blood to the heart muscle cells. Coronary veins remove deoxygenated blood from the heart muscle cells.

  • There are two coronary arteries: a right coronary artery that supplies the right side of the heart and a left coronary artery that supplies the left side of the heart. These arteries branch repeatedly into smaller and smaller arteries and finally into capillaries, which exchange gases, nutrients, and waste products with cardiomyocytes.
  • At the back of the heart, small cardiac veins drain into larger veins and finally into the great cardiac vein, which empties into the right atrium. At the front of the heart, small cardiac veins drain directly into the right atrium.

Blood Circulation Through the Heart

Figure (PageIndex{4}) shows how blood circulates through the chambers of the heart. The right atrium collects blood from two large veins, the superior vena cava (from the upper body) and the inferior vena cava (from the lower body). The blood that collects in the right atrium is pumped through the tricuspid valve into the right ventricle. From the right ventricle, the blood is pumped through the pulmonary valve into the pulmonary artery. The pulmonary artery carries the blood to the lungs, where it enters the pulmonary circulation, gives up carbon dioxide, and picks up oxygen. The oxygenated blood travels back from the lungs through the pulmonary veins (of which there are four) and enters the left atrium of the heart. From the left atrium, the blood is pumped through the mitral valve into the left ventricle. From the left ventricle, the blood is pumped through the aortic valve into the aorta, which subsequently branches into smaller arteries that carry the blood throughout the rest of the body. After passing through capillaries and exchanging substances with cells, the blood returns to the right atrium via the superior vena cava and inferior vena cava, and the process begins anew.

Cardiac Cycle

The cardiac cycle refers to a single complete heartbeat, which includes one iteration of the lub and dub sounds heard through a stethoscope. During the cardiac cycle, the atria and ventricles work in a coordinated fashion so that blood is pumped efficiently through and out of the heart. The cardiac cycle includes two parts, called diastole and systole, which are illustrated in Figure (PageIndex{5}).

  • During diastole, the atria contract and pump blood into the ventricles, while the ventricles relax and fill with blood from the atria.
  • During systole, the atria relax and collect blood from the lungs and body, while the ventricles contract and pump blood out of the heart.

Electrical Stimulation of the Heart

The normal, rhythmical beating of the heart is called sinus rhythm. It is established by the heart’s pacemaker cells, which are located in an area of the heart called the sinoatrial node (Figure (PageIndex{6})). The pacemaker cells create electrical signals by the movement of electrolytes (sodium, potassium, and calcium ions) into and out of the cells. For each cardiac cycle, an electrical signal rapidly travels first from the sinoatrial node to the right and left atria so they contract together. Then the signal travels to another node, called the atrioventricular node (also shown in Figure (PageIndex{6})), and from there to the right and left ventricles, which also contract together, just a split second after the atria contract.

The normal sinus rhythm of the heart is influenced by the autonomic nervous system through sympathetic and parasympathetic nerves. These nerves arise from two paired cardiovascular centers in the medulla of the brainstem. The parasympathetic nerves act to decrease the heart rate, and the sympathetic nerves act to increase the heart rate. Parasympathetic input normally predominates. Without it, the pacemaker cells of the heart would generate a resting heart rate of about 100 beats per minute, instead of a normal resting heart rate of about 72 beats per minute. The cardiovascular centers receive input from receptors throughout the body and act through the sympathetic nerves to increase the heart rate as needed. For example, increased physical activity is detected by receptors in muscles, joints, and tendons. These receptors send nerve impulses to the cardiovascular centers, causing sympathetic nerves to increase the heart rate. This allows more blood to flow to the muscles.

Besides the autonomic nervous system, other factors can also affect the heart rate. For example, thyroid hormones and adrenal hormones such as epinephrine can stimulate the heart to beat faster. The heart rate also increases when blood pressure drops or the body is dehydrated or overheated. On the other hand, cooling of the body and relaxation, among other factors, can contribute to a decrease in the heart rate.

Feature: Human Biology in the News

When a patient’s heart is too diseased or damaged to sustain life, a heart transplant is likely to be the only long-term solution. The first successful heart transplant was undertaken in South Africa in 1967. For the past two decades in the United States, about 2,400 hearts were transplanted each year. The problem is that far too few hearts are available for transplant, and many patients die each year waiting for a life-saving heart to become available.

Hearts for transplant have to be used within four hours of the death of the donor. In addition, hearts can only come from brain-dead individuals whose hearts are removed while they are still healthy. Then the hearts are placed on ice inside picnic coolers to be transported to a waiting recipient. The four-hour window means that traffic jams, bad weather, or other unforeseen delays often result in a heart being in less than optimal condition by the time it arrives at its destination. Unfortunately, there is no way to know if the heart will start up again after it is transplanted until it is actually placed in the recipient’s body. In up to seven percent of cases, a transplanted heart does not work and has to be removed.

A medical device company in Massachusetts named TransMedic was featured in many news stories when it developed the Organ Care System, commonly referred to as “heart in a box.” The system takes a new approach to maintain donated hearts until they are transplanted. The box is heated and contains a device that pumps oxygenated blood through the heart while it is being transported to the recipient. This extends the time up to 12 hours that the heart can remain healthy and usable. It also allows the heart to be monitored so it is kept in optimal condition while it is on the route. The end result, ideally, is that the recipient gets a healthier heart with less chance of failure of the new organ and a lower risk of death.

As of mid-2016, the heart-in-a-box system had already been used for several successful heart transplants in other countries. At that time, the system was also undergoing clinical trials in the United States to assess its effectiveness in promoting positive recipient outcomes. Developers of the heart-in-a-box predict that the system could increase the number of usable donor hearts by as much as 30 percent, thus greatly increasing the number of patients who are saved from death due to heart failure.

Review

  1. What is the heart, where is located, and what is its function?
  2. Outline the structure of the heart.
  3. Describe the coronary circulation.
  4. Summarize how blood flows into, through, and out of the heart.
  5. Define the cardiac cycle, and identify its two parts.
  6. Explain what controls the beating of the heart.
  7. a. What are the two types of cardiac muscle cells in the myocardium?

    b. What are the differences between these two types of cells?

  8. Match each of the three layers of the walls of the heart (endocardium, myocardium, and pericardium) with the description that best matches it below.

    a. Protects the heart

    b. Covers the heart valves

    c. Responsible for the beating of the heart

  9. Is the blood flowing through the mitral valve oxygenated or deoxygenated? Explain your reasoning.

  10. True or False. The coronary arteries carry blood to the heart.

  11. True or False. Systole is when the heart is contracting, diastole is when the heart is fully relaxed.

  12. Explain why the blood from the cardiac veins empties into the right atrium of the heart. Focus on function rather than anatomy in your answer.

Explore More

More women than men die of heart disease, but heart research has long focused on men. In the following TED talk, pioneering doctor C. Noel Bairey Merz shares what we know and don't know about women's heart health, including the very different heart attack symptoms women experience and why doctors often miss them.


17.3 Whole-Genome Sequencing

In this section, you will explore the following questions:

Connection for AP ® Courses

Information presented in section is not in scope for AP ® . However, you can study information in the section as optional or illustrative material.

Teacher Support

With older techniques, identification of pathogenic bacteria is a time consuming process that may take days or weeks. Previously, identification of the tuberculosis bacteria can take up to six weeks. The development of DNA microarrays has enabled clinical laboratories to shorten that time to hours, with better specificity of the identification. This has provided physicians with the information they need to get patients on the most effective antibiotic therapy rapidly, providing better care and preventing the infectious agent from spreading to more hosts.

Although there have been significant advances in the medical sciences in recent years, doctors are still confounded by some diseases, and they are using whole-genome sequencing to get to the bottom of the problem. Whole-genome sequencing is a process that determines the DNA sequence of an entire genome. Whole-genome sequencing is a brute-force approach to problem solving when there is a genetic basis at the core of a disease. Several laboratories now provide services to sequence, analyze, and interpret entire genomes.

Whole-exome sequencing is a lower-cost alternative to whole genome sequencing. In exome sequencing, only the coding, exon-producing regions of the DNA are sequenced. In 2010, whole-exome sequencing was used to save a young boy whose intestines had multiple mysterious abscesses. The child had several colon operations with no relief. Finally, whole-exome sequencing was performed, which revealed a defect in a pathway that controls apoptosis (programmed cell death). A bone-marrow transplant was used to overcome this genetic disorder, leading to a cure for the boy. He was the first person to be successfully treated based on a diagnosis made by whole-exome sequencing.

The Science Practice Challenge Questions contain additional test questions related to the material in this section that will help you prepare for the AP exam. These questions address the following standards:
[APLO 2.23][APLO 3.5][APLO 3.20][APLO 3.21]

Strategies Used in Sequencing Projects

The basic sequencing technique used in all modern day sequencing projects is the chain termination method (also known as the dideoxy method), which was developed by Fred Sanger in the 1970s. The chain termination method involves DNA replication of a single-stranded template with the use of a primer and a regular deoxynucleotide (dNTP), which is a monomer, or a single unit, of DNA. The primer and dNTP are mixed with a small proportion of fluorescently labeled dideoxynucleotides (ddNTPs). The ddNTPs are monomers that are missing a hydroxyl group (–OH) at the site at which another nucleotide usually attaches to form a chain (Figure 17.12). Each ddNTP is labeled with a different color of fluorophore. Every time a ddNTP is incorporated in the growing complementary strand, it terminates the process of DNA replication, which results in multiple short strands of replicated DNA that are each terminated at a different point during replication. When the reaction mixture is processed by gel electrophoresis after being separated into single strands, the multiple newly replicated DNA strands form a ladder because of the differing sizes. Because the ddNTPs are fluorescently labeled, each band on the gel reflects the size of the DNA strand and the ddNTP that terminated the reaction. The different colors of the fluorophore-labeled ddNTPs help identify the ddNTP incorporated at that position. Reading the gel on the basis of the color of each band on the ladder produces the sequence of the template strand (Figure 17.13).

Early Strategies: Shotgun Sequencing and Pair-Wise End Sequencing

In shotgun sequencing method, several copies of a DNA fragment are cut randomly into many smaller pieces (somewhat like what happens to a round shot cartridge when fired from a shotgun). All of the segments are then sequenced using the chain-sequencing method. Then, with the help of a computer, the fragments are analyzed to see where their sequences overlap. By matching up overlapping sequences at the end of each fragment, the entire DNA sequence can be reformed. A larger sequence that is assembled from overlapping shorter sequences is called a contig . As an analogy, consider that someone has four copies of a landscape photograph that you have never seen before and know nothing about how it should appear. The person then rips up each photograph with their hands, so that different size pieces are present from each copy. The person then mixes all of the pieces together and asks you to reconstruct the photograph. In one of the smaller pieces you see a mountain. In a larger piece, you see that the same mountain is behind a lake. A third fragment shows only the lake, but it reveals that there is a cabin on the shore of the lake. Therefore, from looking at the overlapping information in these three fragments, you know that the picture contains a mountain behind a lake that has a cabin on its shore. This is the principle behind reconstructing entire DNA sequences using shotgun sequencing.

Originally, shotgun sequencing only analyzed one end of each fragment for overlaps. This was sufficient for sequencing small genomes. However, the desire to sequence larger genomes, such as that of a human, led to the development of double-barrel shotgun sequencing, more formally known as pairwise-end sequencing . In pairwise-end sequencing, both ends of each fragment are analyzed for overlap. Pairwise-end sequencing is, therefore, more cumbersome than shotgun sequencing, but it is easier to reconstruct the sequence because there is more available information.

Next-generation Sequencing

Since 2005, automated sequencing techniques used by laboratories are under the umbrella of next-generation sequencing , which is a group of automated techniques used for rapid DNA sequencing. These automated low-cost sequencers can generate sequences of hundreds of thousands or millions of short fragments (25 to 500 base pairs) in the span of one day. These sequencers use sophisticated software to get through the cumbersome process of putting all the fragments in order.

Evolution Connection

Comparing Sequences

A sequence alignment is an arrangement of proteins, DNA, or RNA it is used to identify regions of similarity between cell types or species, which may indicate conservation of function or structures. Sequence alignments may be used to construct phylogenetic trees. The following website uses a software program called BLAST (basic local alignment search tool).

Under “Basic Blast,” click “Nucleotide Blast.” Input the following sequence into the large "query sequence" box: ATTGCTTCGATTGCA. Below the box, locate the "Species" field and type "human" or "Homo sapiens". Then click “BLAST” to compare the inputted sequence against known sequences of the human genome. The result is that this sequence occurs in over a hundred places in the human genome. Scroll down below the graphic with the horizontal bars and you will see short description of each of the matching hits. Pick one of the hits near the top of the list and click on "Graphics". This will bring you to a page that shows where the sequence is found within the entire human genome. You can move the slider that looks like a green flag back and forth to view the sequences immediately around the selected gene. You can then return to your selected sequence by clicking the "ATG" button.

  1. The bacterial protein will be more similar to the human protein than the yeast protein.
  2. The bacterial protein will be more similar to the yeast protein than the human protein.
  3. The yeast protein will be more similar to the human protein than the bacterial protein.
  4. The bacterial and yeast protein will share a similar sequence, but the human protein will be unrelated to either.

Use of Whole-Genome Sequences of Model Organisms

The first genome to be completely sequenced was of a bacterial virus, the bacteriophage fx174 (5368 base pairs) this was accomplished by Fred Sanger using shotgun sequencing. Several other organelle and viral genomes were later sequenced. The first organism whose genome was sequenced was the bacterium Haemophilus influenzae this was accomplished by Craig Venter in the 1980s. Approximately 74 different laboratories collaborated on the sequencing of the genome of the yeast Saccharomyces cerevisiae, which began in 1989 and was completed in 1996, because it was 60 times bigger than any other genome that had been sequenced. By 1997, the genome sequences of two important model organisms were available: the bacterium Escherichia coli K12 and the yeast Saccharomyces cerevisiae. Genomes of other model organisms, such as the mouse Mus musculus, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis. elegans, and humans Homo sapiens are now known. A lot of basic research is performed in model organisms because the information can be applied to genetically similar organisms. A model organism is a species that is studied as a model to understand the biological processes in other species represented by the model organism. Having entire genomes sequenced helps with the research efforts in these model organisms. The process of attaching biological information to gene sequences is called genome annotation . Annotation of gene sequences helps with basic experiments in molecular biology, such as designing PCR primers and RNA targets.

Link to Learning

Click through each step of genome sequencing at this site.

Review the Sanger sequencing method as pictured. Make a case for how deep sequencing offers an improvement on Sanger sequencing.

  1. Deep sequencing allows for much faster sequencing of short DNA strands as compared to Sanger sequencing, which reads only short sequences of DNA at a slow rate, and it avoids Sanger's issues with chain termination and separation.
  2. Sequence coverage is higher in Sanger sequencing as compared to deep sequencing.
  3. Sanger sequencing is suitable when there is only one nucleotide difference between chains, whereas deep sequencing is suitable when there is more than one nucleotide difference between chains.
  4. Sanger sequencing reads and sequences a genome multiple times, whereas deep sequencing accurately reads sequences the whole genome in a single time.

Uses of Genome Sequences

DNA microarrays are methods used to detect gene expression by analyzing an array of DNA fragments that are fixed to a glass slide or a silicon chip to identify active genes and identify sequences. Almost one million genotypic abnormalities can be discovered using microarrays, whereas whole-genome sequencing can provide information about all six billion base pairs in the human genome. Although the study of medical applications of genome sequencing is interesting, this discipline tends to dwell on abnormal gene function. Knowledge of the entire genome will allow future onset diseases and other genetic disorders to be discovered early, which will allow for more informed decisions to be made about lifestyle, medication, and having children. Genomics is still in its infancy, although someday it may become routine to use whole-genome sequencing to screen every newborn to detect genetic abnormalities.

In addition to disease and medicine, genomics can contribute to the development of novel enzymes that convert biomass to biofuel, which results in higher crop and fuel production, and lower cost to the consumer. This knowledge should allow better methods of control over the microbes that are used in the production of biofuels. Genomics could also improve the methods used to monitor the impact of pollutants on ecosystems and help clean up environmental contaminants. Genomics has allowed for the development of agrochemicals and pharmaceuticals that could benefit medical science and agriculture.

It sounds great to have all the knowledge we can get from whole-genome sequencing however, humans have a responsibility to use this knowledge wisely. Otherwise, it could be easy to misuse the power of such knowledge, leading to discrimination based on a person's genetics, human genetic engineering, and other ethical concerns. This information could also lead to legal issues regarding health and privacy.


17.3 Whole-Genome Sequencing

By the end of this section, you will be able to do the following:

Although there have been significant advances in the medical sciences in recent years, doctors are still confounded by some diseases, and they are using whole-genome sequencing to discover the root of the problem. Whole-genome sequencing is a process that determines an entire genome’s DNA sequence. Whole-genome sequencing is a brute-force approach to problem solving when there is a genetic basis at the core of a disease. Several laboratories now provide services to sequence, analyze, and interpret entire genomes.

For example, whole-exome sequencing is a lower-cost alternative to whole genome sequencing. In exome sequencing, the doctor sequences only the DNA’s coding, exon-producing regions. In 2010, doctors used whole-exome sequencing to save a young boy whose intestines had multiple mysterious abscesses. The child had several colon operations with no relief. Finally, they performed whole-exome sequencing, which revealed a defect in a pathway that controls apoptosis (programmed cell death). The doctors used a bone-marrow transplant to overcome this genetic disorder, leading to a cure for the boy. He was the first person to receive successful treatment based on a whole-exome sequencing diagnosis. Today, human genome sequencing is more readily available and results are available within two days for about $1000.

Strategies Used in Sequencing Projects

The basic sequencing technique used in all modern day sequencing projects is the chain termination method (also known as the dideoxy method), which Fred Sanger developed in the 1970s. The chain termination method involves DNA replication of a single-stranded template by using a primer and a regular deoxynucleotide (dNTP), which is a monomer, or a single DNA unit. The primer and dNTP mix with a small proportion of fluorescently labeled dideoxynucleotides (ddNTPs). The ddNTPs are monomers that are missing a hydroxyl group (–OH) at the site at which another nucleotide usually attaches to form a chain (Figure 17.13). Scientists label each ddNTP with a different color of fluorophore. Every time a ddNTP incorporates in the growing complementary strand, it terminates the DNA replication process, which results in multiple short strands of replicated DNA that each terminate at a different point during replication. When gel electrophoresis processes the reaction mixture after separating into single strands, the multiple newly replicated DNA strands form a ladder because of the differing sizes. Because the ddNTPs are fluorescently labeled, each band on the gel reflects the DNA strand’s size and the ddNTP that terminated the reaction. The different colors of the fluorophore-labeled ddNTPs help identify the ddNTP incorporated at that position. Reading the gel on the basis of each band’s color on the ladder produces the template strand’s sequence (Figure 17.14).

Early Strategies: Shotgun Sequencing and Pair-Wise End Sequencing

In shotgun sequencing method, several DNA fragment copies cut randomly into many smaller pieces (somewhat like what happens to a round shot cartridge when fired from a shotgun). All of the segments sequence using the chain-sequencing method. Then, with sequence computer assistance, scientists can analyze the fragments to see where their sequences overlap. By matching overlapping sequences at each fragment’s end, scientists can reform the entire DNA sequence. A larger sequence that is assembled from overlapping shorter sequences is called a contig . As an analogy, consider that someone has four copies of a landscape photograph that you have never seen before and know nothing about how it should appear. The person then rips up each photograph with their hands, so that different size pieces are present from each copy. The person then mixes all of the pieces together and asks you to reconstruct the photograph. In one of the smaller pieces you see a mountain. In a larger piece, you see that the same mountain is behind a lake. A third fragment shows only the lake, but it reveals that there is a cabin on the shore of the lake. Therefore, from looking at the overlapping information in these three fragments, you know that the picture contains a mountain behind a lake that has a cabin on its shore. This is the principle behind reconstructing entire DNA sequences using shotgun sequencing.

Originally, shotgun sequencing only analyzed one end of each fragment for overlaps. This was sufficient for sequencing small genomes. However, the desire to sequence larger genomes, such as that of a human, led to developing double-barrel shotgun sequencing, or pairwise-end sequencing . In pairwise-end sequencing, scientists analyze each fragment’s end for overlap. Pairwise-end sequencing is, therefore, more cumbersome than shotgun sequencing, but it is easier to reconstruct the sequence because there is more available information.

Next-generation Sequencing

Since 2005, automated sequencing techniques used by laboratories are under the umbrella of next-generation sequencing , which is a group of automated techniques used for rapid DNA sequencing. These automated low-cost sequencers can generate sequences of hundreds of thousands or millions of short fragments (25 to 500 base pairs) in the span of one day. These sequencers use sophisticated software to get through the cumbersome process of putting all the fragments in order.

Evolution Connection

Comparing Sequences

A sequence alignment is an arrangement of proteins, DNA, or RNA. Scientists use it to identify similar regions between cell types or species, which may indicate function or structure conservation. We can use sequence alignments to construct phylogenetic trees. The following website uses a software program called BLAST (basic local alignment search tool).

Under “Basic Blast,” click “Nucleotide Blast.” Input the following sequence into the large "query sequence" box: ATTGCTTCGATTGCA. Below the box, locate the "Species" field and type "human" or "Homo sapiens". Then click “BLAST” to compare the inputted sequence against the human genome’s known sequences. The result is that this sequence occurs in over a hundred places in the human genome. Scroll down below the graphic with the horizontal bars and you will see a short description of each of the matching hits. Pick one of the hits near the top of the list and click on "Graphics". This will bring you to a page that shows the sequence’s location within the entire human genome. You can move the slider that looks like a green flag back and forth to view the sequences immediately around the selected gene. You can then return to your selected sequence by clicking the "ATG" button.

Use of Whole-Genome Sequences of Model Organisms

British biochemist and Nobel Prize winner Fred Sanger used a bacterial virus, the bacteriophage fx174 (5368 base pairs), to completely sequence the first genome. Other scientists later sequenced several other organelle and viral genomes. American biotechnologist, biochemist, geneticist, and businessman Craig Venter sequenced the bacterium Haemophilus influenzae in the 1980s. Approximately 74 different laboratories collaborated on sequencing the genome of the yeast Saccharomyces cerevisiae, which began in 1989 and was completed in 1996, because it was 60 times bigger than any other genome sequencing. By 1997, the genome sequences of two important model organisms were available: the bacterium Escherichia coli K12 and the yeast Saccharomyces cerevisiae. We now know the genomes of other model organisms, such as the mouse Mus musculus, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis. elegans, and humans Homo sapiens. Researchers perform extensive basic research in model organisms because they can apply the information to genetically similar organisms. A model organism is a species that researchers use as a model to understand the biological processes in other species that the model organism represents. Having entire genomes sequenced helps with the research efforts in these model organisms. The process of attaching biological information to gene sequences is genome annotation . Annotating gene sequences helps with basic experiments in molecular biology, such as designing PCR primers and RNA targets.

Link to Learning

Click through each genome sequencing step at this site.

Genome Sequence Uses

DNA microarrays are methods that scientists use to detect gene expression by analyzing different DNA fragments that are fixed to a glass slide or a silicon chip to identify active genes and sequences. We can discover almost one million genotypic abnormalities using microarrays whereas, whole-genome sequencing can provide information about all six billion base pairs in the human genome. Although studying genome sequencing medical applications is interesting, this discipline dwells on abnormal gene function. Knowing about the entire genome will allow researchers to discover future onset diseases and other genetic disorders early. This will allow for more informed decisions about lifestyle, medication, and having children. Genomics is still in its infancy, although someday it may become routine to use whole-genome sequencing to screen every newborn to detect genetic abnormalities.

In addition to disease and medicine, genomics can contribute to developing novel enzymes that convert biomass to biofuel, which results in higher crop and fuel production, and lower consumer cost. This knowledge should allow better methods of control over the microbes that industry uses to produce biofuels. Genomics could also improve monitoring methods that measure the impact of pollutants on ecosystems and help clean up environmental contaminants. Genomics has aided in developing agrochemicals and pharmaceuticals that could benefit medical science and agriculture.

It sounds great to have all the knowledge we can get from whole-genome sequencing however, humans have a responsibility to use this knowledge wisely. Otherwise, it could be easy to misuse the power of such knowledge, leading to discrimination based on a person's genetics, human genetic engineering, and other ethical concerns. This information could also lead to legal issues regarding health and privacy.


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17.3: Heart - Biology

For years, scientists have known about the relationship between depression and heart disease. At least a quarter of cardiac patients suffer with depression, and adults with depression often develop heart disease. What researchers now want to know is “why.” So far, they have unearthed a treasure trove of important clues, but a definitive explanation on the curious nature of this relationship has yet to emerge.

It is a puzzle: Is depression a causal risk factor for heart disease? Is it a warning sign because depressed people engage in behaviors that increase the risks for heart disease? Is depression just a secondary event, prompted by the trauma of major medical problems, such as heart surgery? Experts say the urgent need for answers is clear: According to the World Health Organization, 350 million people suffer from depression worldwide, and 17.3 million die of heart disease each year, making it the number one global cause of death.

The promising news, they say, is that new insights are emerging because of the data researchers continue to amass, scientific innovation, and heightened public awareness. It was in part because of better diagnostic tools and an increased recognition of the prevalence of depression that scientists could establish a connection between depression and heart disease in the first place.

“Thirty years of epidemiological data indicate that depression does predict the development of heart disease,” said Jesse C. Stewart, Ph.D., an associate professor of psychology in the School of Science at Indiana University-Purdue University Indianapolis (IUPUI).

Stewart noted that there is now “an impressive body of evidence” showing that, compared with people without depression, adults with a depressive disorder or symptoms have a 64 percent greater risk of developing coronary artery disease (CAD) and depressed CAD patients are 59 percent more likely to have a future adverse cardiovascular event, such as a heart attack or cardiac death.

But, does depression cause heart disease? Is it a risk factor on its own?

Many investigators recoil at the use of the word "cause" because almost all evidence connecting heart disease and depression comes from observational studies.

“Those who have elevated depressive symptoms are at increased risk for heart disease, and this association seems to be largely independent of the traditional risk markers for heart disease,” said Karina W. Davidson, Ph.D., professor at Columbia University Medical Center. Indeed, she said, the association between depression and heart disease is similar to the association of factors such as high cholesterol, hypertension, diabetes, smoking, and obesity and heart disease.

To establish a true cause-effect link between depression and heart disease, according to Stewart, scientists need evidence from randomized controlled trials showing that treating depression reduces the risk of future heart disease. In other words, what needs to be studied is whether treating depression prevents heart disease in the way treating high cholesterol and blood pressure does.

A 2014 paper by Stewart and his colleagues suggests that early treatment for depression, before the development of symptomatic cardiovascular disease, could decrease the risk of heart attacks and strokes by almost half. Now, with funding from the National Heart, Lung, and Blood Institute (NHLBI), Stewart is currently conducting the clinical trial he said would help answer this cause-effect question.

In the meantime, the existing evidence prompted the American Heart Association (AHA) to issue a statement in 2015 warning that teens with depression and bipolar disorder stand at increased risk for developing cardiovascular disease earlier in life, and urging doctors to actively monitor these patients and intervene to try to prevent its onset.

The prevalence of depression among cardiac patients ranges from 20 to 30 percent. “Even the lower limit of this ranges is more than double the prevalence of this treatable condition in the general population,” wrote Bruce L. Rollman, M.D. and Stewart in their 2014 study.

A recent study presented at the American College of Cardiology’s 66th Annual Scientific Session shows that patients are twice as likely to die if they develop depression after being diagnosed with heart disease. In fact, depression is the strongest predictor of death in the first decade after a heart disease diagnosis.

“We are confident that depression is an independent risk factor for cardiac morbidity and mortality in patients with established heart disease,” said Robert Carney, Ph.D., professor of psychiatry at Washington University School of Medicine. “However, depression is also associated with other risk factors, including smoking, so it can be difficult to disentangle its effects from those of other risk factors.”

In other words, cardiac patients with depression have worse outcomes, which translate to more deaths and repeated cardiovascular events. But how does depression have such an effect?

Researchers agree that while the pathways are not completely understood, there are many likely explanations. Some point to the biology of depression, such as autonomic nervous system dysfunction, elevated cortisol levels, and elevated markers of inflammation.

“There are also plausible behavioral explanations, such as poor adherence to diet, exercise, and medications, and a higher prevalence of smoking, that have been associated with depression with or without established heart disease,” said Ken Freedland, Ph.D., also from Washington University School of Medicine.

“We think that there are likely to be multiple pathways, and this has been one of the foci of our research over the years,” he said.


Pheromones

A pheromone is a chemical released by an animal that affects the behavior or physiology of animals of the same species. Pheromonal signals can have profound effects on animals that inhale them, but pheromones apparently are not consciously perceived in the same way as other odors. There are several different types of pheromones, which are released in urine or as glandular secretions. Certain pheromones are attractants to potential mates, others are repellants to potential competitors of the same sex, and still others play roles in mother-infant attachment. Some pheromones can also influence the timing of puberty, modify reproductive cycles, and even prevent embryonic implantation. While the roles of pheromones in many nonhuman species are important, pheromones have become less important in human behavior over evolutionary time compared to their importance to organisms with more limited behavioral repertoires.

The vomeronasal organ (VNO, or Jacobson’s organ) is a tubular, fluid-filled, olfactory organ present in many vertebrate animals that sits adjacent to the nasal cavity. It is very sensitive to pheromones and is connected to the nasal cavity by a duct. When molecules dissolve in the mucosa of the nasal cavity, they then enter the VNO where the pheromone molecules among them bind with specialized pheromone receptors. Upon exposure to pheromones from their own species or others, many animals, including cats, may display the flehmen response (shown in Figure 17.9), a curling of the upper lip that helps pheromone molecules enter the VNO.

Pheromonal signals are sent, not to the main olfactory bulb, but to a different neural structure that projects directly to the amygdala (recall that the amygdala is a brain center important in emotional reactions, such as fear). The pheromonal signal then continues to areas of the hypothalamus that are key to reproductive physiology and behavior. While some scientists assert that the VNO is apparently functionally vestigial in humans, even though there is a similar structure located near human nasal cavities, others are researching it as a possible functional system that may, for example, contribute to synchronization of menstrual cycles in women living in close proximity.

Figure 17.9.
The flehmen response in this tiger results in the curling of the upper lip and helps airborne pheromone molecules enter the vomeronasal organ. (credit: modification of work by “chadh”/Flickr)


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