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17.3 Whole-Genome Sequencing

Biology17.3 Whole-Genome Sequencing

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Table of contents
  1. Preface
  2. Unit 1. The Chemistry of Life
    1. 1 The Study of Life
      1. Introduction
      2. 1.1 The Science of Biology
      3. 1.2 Themes and Concepts of Biology
      4. Key Terms
      5. Chapter Summary
      6. Visual Connection Questions
      7. Review Questions
      8. Critical Thinking Questions
    2. 2 The Chemical Foundation of Life
      1. Introduction
      2. 2.1 Atoms, Isotopes, Ions, and Molecules: The Building Blocks
      3. 2.2 Water
      4. 2.3 Carbon
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    3. 3 Biological Macromolecules
      1. Introduction
      2. 3.1 Synthesis of Biological Macromolecules
      3. 3.2 Carbohydrates
      4. 3.3 Lipids
      5. 3.4 Proteins
      6. 3.5 Nucleic Acids
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
  3. Unit 2. The Cell
    1. 4 Cell Structure
      1. Introduction
      2. 4.1 Studying Cells
      3. 4.2 Prokaryotic Cells
      4. 4.3 Eukaryotic Cells
      5. 4.4 The Endomembrane System and Proteins
      6. 4.5 The Cytoskeleton
      7. 4.6 Connections between Cells and Cellular Activities
      8. Key Terms
      9. Chapter Summary
      10. Visual Connection Questions
      11. Review Questions
      12. Critical Thinking Questions
    2. 5 Structure and Function of Plasma Membranes
      1. Introduction
      2. 5.1 Components and Structure
      3. 5.2 Passive Transport
      4. 5.3 Active Transport
      5. 5.4 Bulk Transport
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    3. 6 Metabolism
      1. Introduction
      2. 6.1 Energy and Metabolism
      3. 6.2 Potential, Kinetic, Free, and Activation Energy
      4. 6.3 The Laws of Thermodynamics
      5. 6.4 ATP: Adenosine Triphosphate
      6. 6.5 Enzymes
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    4. 7 Cellular Respiration
      1. Introduction
      2. 7.1 Energy in Living Systems
      3. 7.2 Glycolysis
      4. 7.3 Oxidation of Pyruvate and the Citric Acid Cycle
      5. 7.4 Oxidative Phosphorylation
      6. 7.5 Metabolism without Oxygen
      7. 7.6 Connections of Carbohydrate, Protein, and Lipid Metabolic Pathways
      8. 7.7 Regulation of Cellular Respiration
      9. Key Terms
      10. Chapter Summary
      11. Visual Connection Questions
      12. Review Questions
      13. Critical Thinking Questions
    5. 8 Photosynthesis
      1. Introduction
      2. 8.1 Overview of Photosynthesis
      3. 8.2 The Light-Dependent Reactions of Photosynthesis
      4. 8.3 Using Light Energy to Make Organic Molecules
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    6. 9 Cell Communication
      1. Introduction
      2. 9.1 Signaling Molecules and Cellular Receptors
      3. 9.2 Propagation of the Signal
      4. 9.3 Response to the Signal
      5. 9.4 Signaling in Single-Celled Organisms
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    7. 10 Cell Reproduction
      1. Introduction
      2. 10.1 Cell Division
      3. 10.2 The Cell Cycle
      4. 10.3 Control of the Cell Cycle
      5. 10.4 Cancer and the Cell Cycle
      6. 10.5 Prokaryotic Cell Division
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
  4. Unit 3. Genetics
    1. 11 Meiosis and Sexual Reproduction
      1. Introduction
      2. 11.1 The Process of Meiosis
      3. 11.2 Sexual Reproduction
      4. Key Terms
      5. Chapter Summary
      6. Visual Connection Questions
      7. Review Questions
      8. Critical Thinking Questions
    2. 12 Mendel's Experiments and Heredity
      1. Introduction
      2. 12.1 Mendel’s Experiments and the Laws of Probability
      3. 12.2 Characteristics and Traits
      4. 12.3 Laws of Inheritance
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    3. 13 Modern Understandings of Inheritance
      1. Introduction
      2. 13.1 Chromosomal Theory and Genetic Linkage
      3. 13.2 Chromosomal Basis of Inherited Disorders
      4. Key Terms
      5. Chapter Summary
      6. Visual Connection Questions
      7. Review Questions
      8. Critical Thinking Questions
    4. 14 DNA Structure and Function
      1. Introduction
      2. 14.1 Historical Basis of Modern Understanding
      3. 14.2 DNA Structure and Sequencing
      4. 14.3 Basics of DNA Replication
      5. 14.4 DNA Replication in Prokaryotes
      6. 14.5 DNA Replication in Eukaryotes
      7. 14.6 DNA Repair
      8. Key Terms
      9. Chapter Summary
      10. Visual Connection Questions
      11. Review Questions
      12. Critical Thinking Questions
    5. 15 Genes and Proteins
      1. Introduction
      2. 15.1 The Genetic Code
      3. 15.2 Prokaryotic Transcription
      4. 15.3 Eukaryotic Transcription
      5. 15.4 RNA Processing in Eukaryotes
      6. 15.5 Ribosomes and Protein Synthesis
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    6. 16 Gene Expression
      1. Introduction
      2. 16.1 Regulation of Gene Expression
      3. 16.2 Prokaryotic Gene Regulation
      4. 16.3 Eukaryotic Epigenetic Gene Regulation
      5. 16.4 Eukaryotic Transcription Gene Regulation
      6. 16.5 Eukaryotic Post-transcriptional Gene Regulation
      7. 16.6 Eukaryotic Translational and Post-translational Gene Regulation
      8. 16.7 Cancer and Gene Regulation
      9. Key Terms
      10. Chapter Summary
      11. Visual Connection Questions
      12. Review Questions
      13. Critical Thinking Questions
    7. 17 Biotechnology and Genomics
      1. Introduction
      2. 17.1 Biotechnology
      3. 17.2 Mapping Genomes
      4. 17.3 Whole-Genome Sequencing
      5. 17.4 Applying Genomics
      6. 17.5 Genomics and Proteomics
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
  5. Unit 4. Evolutionary Processes
    1. 18 Evolution and the Origin of Species
      1. Introduction
      2. 18.1 Understanding Evolution
      3. 18.2 Formation of New Species
      4. 18.3 Reconnection and Rates of Speciation
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    2. 19 The Evolution of Populations
      1. Introduction
      2. 19.1 Population Evolution
      3. 19.2 Population Genetics
      4. 19.3 Adaptive Evolution
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    3. 20 Phylogenies and the History of Life
      1. Introduction
      2. 20.1 Organizing Life on Earth
      3. 20.2 Determining Evolutionary Relationships
      4. 20.3 Perspectives on the Phylogenetic Tree
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
  6. Unit 5. Biological Diversity
    1. 21 Viruses
      1. Introduction
      2. 21.1 Viral Evolution, Morphology, and Classification
      3. 21.2 Virus Infections and Hosts
      4. 21.3 Prevention and Treatment of Viral Infections
      5. 21.4 Other Acellular Entities: Prions and Viroids
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    2. 22 Prokaryotes: Bacteria and Archaea
      1. Introduction
      2. 22.1 Prokaryotic Diversity
      3. 22.2 Structure of Prokaryotes
      4. 22.3 Prokaryotic Metabolism
      5. 22.4 Bacterial Diseases in Humans
      6. 22.5 Beneficial Prokaryotes
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    3. 23 Protists
      1. Introduction
      2. 23.1 Eukaryotic Origins
      3. 23.2 Characteristics of Protists
      4. 23.3 Groups of Protists
      5. 23.4 Ecology of Protists
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    4. 24 Fungi
      1. Introduction
      2. 24.1 Characteristics of Fungi
      3. 24.2 Classifications of Fungi
      4. 24.3 Ecology of Fungi
      5. 24.4 Fungal Parasites and Pathogens
      6. 24.5 Importance of Fungi in Human Life
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    5. 25 Seedless Plants
      1. Introduction
      2. 25.1 Early Plant Life
      3. 25.2 Green Algae: Precursors of Land Plants
      4. 25.3 Bryophytes
      5. 25.4 Seedless Vascular Plants
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    6. 26 Seed Plants
      1. Introduction
      2. 26.1 Evolution of Seed Plants
      3. 26.2 Gymnosperms
      4. 26.3 Angiosperms
      5. 26.4 The Role of Seed Plants
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    7. 27 Introduction to Animal Diversity
      1. Introduction
      2. 27.1 Features of the Animal Kingdom
      3. 27.2 Features Used to Classify Animals
      4. 27.3 Animal Phylogeny
      5. 27.4 The Evolutionary History of the Animal Kingdom
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    8. 28 Invertebrates
      1. Introduction
      2. 28.1 Phylum Porifera
      3. 28.2 Phylum Cnidaria
      4. 28.3 Superphylum Lophotrochozoa
      5. 28.4 Superphylum Ecdysozoa
      6. 28.5 Superphylum Deuterostomia
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    9. 29 Vertebrates
      1. Introduction
      2. 29.1 Chordates
      3. 29.2 Fishes
      4. 29.3 Amphibians
      5. 29.4 Reptiles
      6. 29.5 Birds
      7. 29.6 Mammals
      8. 29.7 The Evolution of Primates
      9. Key Terms
      10. Chapter Summary
      11. Visual Connection Questions
      12. Review Questions
      13. Critical Thinking Questions
  7. Unit 6. Plant Structure and Function
    1. 30 Plant Form and Physiology
      1. Introduction
      2. 30.1 The Plant Body
      3. 30.2 Stems
      4. 30.3 Roots
      5. 30.4 Leaves
      6. 30.5 Transport of Water and Solutes in Plants
      7. 30.6 Plant Sensory Systems and Responses
      8. Key Terms
      9. Chapter Summary
      10. Visual Connection Questions
      11. Review Questions
      12. Critical Thinking Questions
    2. 31 Soil and Plant Nutrition
      1. Introduction
      2. 31.1 Nutritional Requirements of Plants
      3. 31.2 The Soil
      4. 31.3 Nutritional Adaptations of Plants
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    3. 32 Plant Reproduction
      1. Introduction
      2. 32.1 Reproductive Development and Structure
      3. 32.2 Pollination and Fertilization
      4. 32.3 Asexual Reproduction
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
  8. Unit 7. Animal Structure and Function
    1. 33 The Animal Body: Basic Form and Function
      1. Introduction
      2. 33.1 Animal Form and Function
      3. 33.2 Animal Primary Tissues
      4. 33.3 Homeostasis
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    2. 34 Animal Nutrition and the Digestive System
      1. Introduction
      2. 34.1 Digestive Systems
      3. 34.2 Nutrition and Energy Production
      4. 34.3 Digestive System Processes
      5. 34.4 Digestive System Regulation
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    3. 35 The Nervous System
      1. Introduction
      2. 35.1 Neurons and Glial Cells
      3. 35.2 How Neurons Communicate
      4. 35.3 The Central Nervous System
      5. 35.4 The Peripheral Nervous System
      6. 35.5 Nervous System Disorders
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    4. 36 Sensory Systems
      1. Introduction
      2. 36.1 Sensory Processes
      3. 36.2 Somatosensation
      4. 36.3 Taste and Smell
      5. 36.4 Hearing and Vestibular Sensation
      6. 36.5 Vision
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    5. 37 The Endocrine System
      1. Introduction
      2. 37.1 Types of Hormones
      3. 37.2 How Hormones Work
      4. 37.3 Regulation of Body Processes
      5. 37.4 Regulation of Hormone Production
      6. 37.5 Endocrine Glands
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    6. 38 The Musculoskeletal System
      1. Introduction
      2. 38.1 Types of Skeletal Systems
      3. 38.2 Bone
      4. 38.3 Joints and Skeletal Movement
      5. 38.4 Muscle Contraction and Locomotion
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    7. 39 The Respiratory System
      1. Introduction
      2. 39.1 Systems of Gas Exchange
      3. 39.2 Gas Exchange across Respiratory Surfaces
      4. 39.3 Breathing
      5. 39.4 Transport of Gases in Human Bodily Fluids
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    8. 40 The Circulatory System
      1. Introduction
      2. 40.1 Overview of the Circulatory System
      3. 40.2 Components of the Blood
      4. 40.3 Mammalian Heart and Blood Vessels
      5. 40.4 Blood Flow and Blood Pressure Regulation
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    9. 41 Osmotic Regulation and Excretion
      1. Introduction
      2. 41.1 Osmoregulation and Osmotic Balance
      3. 41.2 The Kidneys and Osmoregulatory Organs
      4. 41.3 Excretion Systems
      5. 41.4 Nitrogenous Wastes
      6. 41.5 Hormonal Control of Osmoregulatory Functions
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    10. 42 The Immune System
      1. Introduction
      2. 42.1 Innate Immune Response
      3. 42.2 Adaptive Immune Response
      4. 42.3 Antibodies
      5. 42.4 Disruptions in the Immune System
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
    11. 43 Animal Reproduction and Development
      1. Introduction
      2. 43.1 Reproduction Methods
      3. 43.2 Fertilization
      4. 43.3 Human Reproductive Anatomy and Gametogenesis
      5. 43.4 Hormonal Control of Human Reproduction
      6. 43.5 Human Pregnancy and Birth
      7. 43.6 Fertilization and Early Embryonic Development
      8. 43.7 Organogenesis and Vertebrate Formation
      9. Key Terms
      10. Chapter Summary
      11. Visual Connection Questions
      12. Review Questions
      13. Critical Thinking Questions
  9. Unit 8. Ecology
    1. 44 Ecology and the Biosphere
      1. Introduction
      2. 44.1 The Scope of Ecology
      3. 44.2 Biogeography
      4. 44.3 Terrestrial Biomes
      5. 44.4 Aquatic Biomes
      6. 44.5 Climate and the Effects of Global Climate Change
      7. Key Terms
      8. Chapter Summary
      9. Visual Connection Questions
      10. Review Questions
      11. Critical Thinking Questions
    2. 45 Population and Community Ecology
      1. Introduction
      2. 45.1 Population Demography
      3. 45.2 Life Histories and Natural Selection
      4. 45.3 Environmental Limits to Population Growth
      5. 45.4 Population Dynamics and Regulation
      6. 45.5 Human Population Growth
      7. 45.6 Community Ecology
      8. 45.7 Behavioral Biology: Proximate and Ultimate Causes of Behavior
      9. Key Terms
      10. Chapter Summary
      11. Visual Connection Questions
      12. Review Questions
      13. Critical Thinking Questions
    3. 46 Ecosystems
      1. Introduction
      2. 46.1 Ecology of Ecosystems
      3. 46.2 Energy Flow through Ecosystems
      4. 46.3 Biogeochemical Cycles
      5. Key Terms
      6. Chapter Summary
      7. Visual Connection Questions
      8. Review Questions
      9. Critical Thinking Questions
    4. 47 Conservation Biology and Biodiversity
      1. Introduction
      2. 47.1 The Biodiversity Crisis
      3. 47.2 The Importance of Biodiversity to Human Life
      4. 47.3 Threats to Biodiversity
      5. 47.4 Preserving Biodiversity
      6. Key Terms
      7. Chapter Summary
      8. Visual Connection Questions
      9. Review Questions
      10. Critical Thinking Questions
  10. A | The Periodic Table of Elements
  11. B | Geological Time
  12. C | Measurements and the Metric System
  13. Index

Learning Objectives

By the end of this section, you will be able to:
  • Describe three types of sequencing
  • Define whole-genome sequencing

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.

For example, 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. Today, human genome sequencing is more readily available and can be completed in a day or two 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 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 17.13). 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 17.14).

A deoxynucleotide consists of a deoxyribose sugar, a base, and three phosphate groups. Dideoxyribose is identical to deoxyribose except that the hydroxyl (–OH) group at the 3' position is replaced by H. A 3' hydroxyl is necessary for elongation of the DNA chain, and the chain therefore stops growing if a dideoxyribose instead of deoxyribose is incorporated into the growing chain.
Figure 17.13 A dideoxynucleotide is similar in structure to a deoxynucleotide, but is missing the 3' hydroxyl group (indicated by the box). When a dideoxynucleotide is incorporated into a DNA strand, DNA synthesis stops.
The left part of this illustration shows a parent strand of DNA with the sequence GATTCAGC, and four daughter strands, each of which was made in the presence of a different dideoxynucleotide: ddATP, ddCTP, ddGTP, or ddTTP. The growing chain terminates when a ddNTP is incorporated, resulting in daughter strands of different lengths. The right part of this image shows the separation of the DNA fragments on the basis of size. Each ddNTP is fluorescently labeled with a different color so that the sequence can be read by the size of each fragment and its color.
Figure 17.14 Frederick Sanger's dideoxy chain termination method is illustrated. Using dideoxynucleotides, the DNA fragment can be terminated at different points. The DNA is separated on the basis of size, and these bands, based on the size of the fragments, can be read.

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

Evolution Connection

Comparing SequencesA 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.

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

Link to Learning

QR Code representing a URL

Click through each step of genome sequencing at this site.

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.

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