1: Introduction to Genetics Flashcards
______ in the twenty-first century is built on a rich tradition of discovery and experimentation stretching from the ancient world through the nineteenth century to the present day.
Genetics
______ is the general process by which traits controlled by genes are transmitted through gametes from generation to generation.
Transmission genetics
______ can be used in genetic crosses to map the location and distance between genes on chromosomes.
Mutant strains
The ______ structure explains how genetic information is stored and expressed. This discovery is the foundation of ______.
Watson–Crick model of DNA, molecular genetics
______ revolutionized genetics, was the foundation for the ______, and has generated new fields that combine genetics with information technology.
Recombinant DNA technology, Human Genome Project
______ provides genetically modified organisms and their products that are used across a wide range of fields including agriculture, medicine, and industry.
Biotechnology
Model organisms used in genetics research are now utilized in combination with ______ and ______ to study human diseases.
recombinant DNA technology, genomics
______ is developing faster than the policies, laws, and conventions that govern its use.
Genetic technology
In this edition, we are fortunate to be able to discuss the discovery of ______, a molecular complex found in bacteria that has the potential to revolutionize our ability to rewrite the DNA sequence of genes from any organism. As such, it represents the ultimate tool in ______, whereby the genome of organisms, including humans, may be precisely edited. Such gene modification represents the ultimate application of the many advances in biotechnology made in the last 35 years, including the sequencing of the ______.
CRISPR-Cas, genetic technology, human genome
Other systems have been developed, including ______ and ______, that are now undergoing clinical trials for the treatment of human diseases, and which we will discuss later in the text.
zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs)
However, the ______ system is the most powerful and far-reaching method and is now the preferred approach in gene modification. This system allows researchers to edit genomes with greater accuracy, is easier to use, and is more versatile than the ZFN or TALEN systems.
CRISPR-Cas
CRISPR-Cas molecules were initially discovered as a molecular complex that protects ______ cells from invasion by ______.
bacterial, viruses
CRISPR (______) designates an ______ molecule, which in the laboratory can be synthesized to match any ______ sequence of choice.
clustered regularly interspersed short palindromic repeats, RNA, DNA
CRISPR RNA has two ends: one recognizes and binds to a matching ______ sequence in the gene of interest, and the other binds to a ______ nuclease, or ______ enzyme.
DNA, CRISPR-associated (Cas), DNA-cutting
The most commonly used Cas nuclease is ______, but there are many other Cas nucleases, each of which has slightly different properties, contributing to the system’s versatility.
Cas9
In laboratory experiments, ______ systems have already been used to repair mutations in cells derived from individuals with several genetic disorders, including cystic fibrosis, Huntington disease, beta-thalassemia, sickle cell disease, muscular dystrophy, and X-linked retinitis pigmentosa, which results in progressive vision loss.
CRISPR-Cas
In the United States a clinical trial using CRISPR-Cas9 for genome editing in ______ therapy has been approved, and a second proposal for treating a genetic form of ______ is in preparation.
cancer, blindness
A clinical trial using CRISPR-Cas9 for cancer therapy is already under way in ______.
China
We don’t know when people first recognized the hereditary nature of certain traits, but ______ (e.g., pictorial representations, preserved bones and skulls, and dried seeds) documents the successful domestication of animals and the cultivation of plants thousands of years ago by the ______ of genetic variants from wild populations.
archaeological evidence, artificial selection
Between ______ and ______ b.c., horses, camels, oxen, and wolves were domesticated, and selective breeding of these species soon followed.
8000, 1000
Cultivation of many plants, including maize, wheat, rice, and the date palm, began around ______ b.c. Such evidence documents our ancestors’ successful attempts to manipulate the genetic composition of species.
5000
During the Golden Age of Greek culture, the writings of the ______ (500–400 b.c.) and of the philosopher and naturalist ______ (384–322 b.c.) discussed heredity as it relates to humans.
Hippocratic School of Medicine, Aristotle
The Hippocratic treatise ______ argued that active “______” in various parts of the body served as the bearers of hereditary traits.
On the Seed, humors
Drawn from various parts of the male body to the semen and passed on to offspring, these humors could be healthy or diseased, with the diseased humors accounting for the appearance of newborns with congenital ______ or ______. It was also believed that these humors could be altered in individuals before they were passed on to offspring, explaining how newborns could “______” traits that their parents had “______” in response to their environment.
disorders, deformities, inherit, acquired
Aristotle extended Hippocrates’ thinking and proposed that the male semen contained a “______” with the capacity to produce offspring of the same “______” (i.e., basic structure and capacities) as the parent.
vital heat, form
Aristotle believed that this heat cooked and shaped the menstrual blood produced by the female, which was the “______” that gave rise to an offspring. The embryo developed not because it already contained the parts of an adult in ______ form (as some Hippocratics had thought) but because of the shaping power of the vital heat.
physical substance, miniature
Although the ideas of ______ and ______ sound primitive and naive today, we should recall that prior to the 1800s neither sperm nor eggs had been observed in mammals.
Hippocrates, Aristotle
______–______: The Dawn of Modern Biology
1600, 1850
1600–1850: The Dawn of Modern Biology
Between about 300 b.c. and 1600 a.d., there were few significant new ideas about genetics. However, between 1600 and 1850, major strides provided insight into the biological basis of life. In the 1600s, ______ studied reproduction and development and proposed the theory of ______, which states that an organism develops from the fertilized egg by a succession of developmental events that eventually transform the egg into an adult.
William Harvey, epigenesis
1600–1850: The Dawn of Modern Biology
The theory of epigenesis directly conflicted with the ______, which stated that the fertilized egg contains a complete miniature adult, called a ______.
theory of preformation, homunculus
1600–1850: The Dawn of Modern Biology
Around 1830, ______ and ______ proposed the ______, stating that all organisms are composed of basic structural units called cells, which are derived from ______.
Matthias Schleiden, Theodor Schwann, cell theory, preexisting cells
1600–1850: The Dawn of Modern Biology
The idea of ______, the creation of living organisms from nonliving components, was disproved by ______ later in the century, and living organisms were then considered to be derived from pre-existing organisms and to consist of cells.
spontaneous generation, Louis Pasteur
1600–1850: The Dawn of Modern Biology
In the mid-1800s the revolutionary work of ______ and ______ set the stage for the rapid development of genetics in the twentieth and twenty-first centuries.
Charles Darwin, Gregor Mendel
Charles Darwin and Evolution
With this background, we turn to a brief discussion of the work of Charles Darwin, who published ______, in ______, describing his ideas about evolution.
The Origin of Species, 1859
Charles Darwin and Evolution
Darwin’s geological, geographical, and biological observations convinced him that existing species arose by ______ with ______ from ancestral species.
descent, modification
Charles Darwin and Evolution
Greatly influenced by his voyage on the ______ (1831–1836), Darwin’s thinking led him to formulate the ______, which presented an explanation of the mechanism of evolutionary change.
HMS Beagle, theory of natural selection
Charles Darwin and Evolution
Formulated and proposed independently by ______, ______ is based on the observation that populations tend to contain more offspring than the environment can support, leading to a struggle for survival among individuals.
Alfred Russel Wallace, natural selection
Charles Darwin and Evolution
Those individuals with heritable traits that allow them to adapt to their ______ are better able to survive and reproduce than those with less adaptive traits. Over a long period of time, advantageous variations, even very slight ones, will accumulate. If a population carrying these inherited variations becomes reproductively isolated, a new species may result.
environment
Charles Darwin and Evolution
Darwin, however, lacked an understanding of the genetic basis of ______ and ______, a gap that left his theory open to reasonable criticism well into the twentieth century.
variation, inheritance
Charles Darwin and Evolution
Shortly after Darwin published his book, ______ published a paper in ______ showing how traits were passed from generation to generation in pea plants and offering a general model of how traits are inherited. His research was little known until it was partially duplicated and brought to light by ______, ______, and ______ around ______.
Gregor Johann Mendel, 1866, Carl Correns, Hugo de Vries, Erich Tschermak, 1900
Charles Darwin and Evolution
By the early part of the twentieth century, it became clear that heredity and development were dependent on genetic information residing in ______ contained in ______, which were then contributed to each individual by ______—the so-called ______. The gap in Darwin’s theory was closed, and Mendel’s research has continued to serve as the foundation of genetics.
genes, chromosomes, gametes, chromosomal theory of inheritance
Because genetic processes are fundamental to life itself, the science of genetics unifies ______ and serves as its core. The starting point for this branch of science was a ______ in ______ in the late ______.
biology, monastery garden, central Europe, 1850s
Mendel’s Work on Transmission of Traits
______, an Augustinian monk, conducted a decade-long series of experiments using pea plants. He applied quantitative data analysis to his results and showed that traits are passed from ______ to ______ in predictable ways.
Gregor Mendel, parents, offspring
Mendel’s Work on Transmission of Traits
He further concluded that each trait in the plant is controlled by a pair of factors (which we now call ______) and that during ______ (the formation of egg cells and sperm), members of a gene pair ______ from each other.
genes, gamete formation, separate
Mendel’s Work on Transmission of Traits
His work was published in ______ but was largely unknown until it was cited in papers published by others around ______.
1866, 1900
Mendel’s Work on Transmission of Traits
Once confirmed, Mendel’s findings became recognized as explaining the transmission of traits in ______ plants and all other higher organisms. His work forms the foundation for ______, which is defined as the branch of biology concerned with the study of heredity and variation.
pea, genetics
______: Uniting Mendel and Meiosis
The Chromosome Theory of Inheritance
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
Mendel did his experiments before the structure and role of chromosomes were known. About ______ years after his work was published, advances in microscopy allowed researchers to identify chromosomes and establish that, in most ______, members of each species have a characteristic number of chromosomes called the ______ (2n) in most of their cells.
20, eukaryotes, diploid number
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
For example, humans have a diploid number of ______. Chromosomes in diploid cells exist in pairs, called ______.
46, homologous chromosomes
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
Researchers in the last decades of the nineteenth century also described chromosome behavior during two forms of cell division, ______ and ______.
mitosis, meiosis
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
In mitosis, chromosomes are copied and distributed so that each daughter cell receives a ______ set of chromosomes ______ to those in the parental cell.
diploid, identical
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
Meiosis is associated with ______.
gamete formation
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
Cells produced by meiosis receive only ______ chromosome from each chromosome pair, and the resulting number of chromosomes is called the ______ (n). This reduction in chromosome number is essential if the offspring arising from the fusion of egg and sperm are to maintain the ______ number of chromosomes characteristic of their parents and other members of their species.
one, haploid number, constant
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
Early in the twentieth century, ______ and ______ independently noted that the behavior of chromosomes during meiosis is identical to the behavior of genes during ______ described by Mendel. For example, genes and chromosomes exist in pairs, and members of a gene pair and members of a chromosome pair ______ from each other during gamete formation.
Walter Sutton, Theodor Boveri, gamete formation, separate
The Chromosome Theory of Inheritance:
Uniting Mendel and Meiosis
Based on these and other parallels, ______ and ______ each proposed that genes are carried on chromosomes. They independently formulated the ______, which states that inherited traits are controlled by ______ residing on ______ faithfully transmitted through ______, maintaining genetic continuity from generation to generation.
Sutton, Boveri, chromosome theory of inheritance, genes, chromosomes, gametes
Genetic Variation
About the same time that the chromosome theory of inheritance was proposed, scientists began studying the inheritance of traits in the fruit fly, ______. Early in this work, a white-eyed fly was discovered among normal (wild-type) red-eyed flies. This variation was produced by a ______ in one of the genes controlling ______.
Drosophila melanogaster, mutation, eye color
Genetic Variation
______ are defined as any heritable change in the DNA sequence and are the source of all genetic variation.
Mutations
Genetic Variation
The white-eye variant discovered in Drosophila is an ______ of a gene controlling eye color.
allele
Genetic Variation
______ are defined as alternative forms of a gene.
Alleles
Genetic Variation
Different alleles may produce differences in the observable features, or ______, of an organism.
phenotype
Genetic Variation
The set of alleles for a given trait carried by an organism is called the ______.
genotype
Genetic Variation
Using ______ as markers, geneticists can map the location of genes on chromosomes.
mutant genes
The Search for the Chemical Nature
of Genes: DNA or Protein?
Work on white-eyed Drosophila showed that the mutant trait could be traced to a single chromosome, confirming the idea that ______ are carried on ______. Once this relationship was established, investigators turned their attention to identifying which chemical component of chromosomes carries ______.
genes, chromosomes, genetic information
The Search for the Chemical Nature
of Genes: DNA or Protein?
By the 1920s, scientists knew that ______ and ______ were the major chemical components of chromosomes.
proteins, DNA
The Search for the Chemical Nature
of Genes: DNA or Protein?
There are a large number of different proteins, and because of their universal distribution in the ______ and ______, many researchers thought proteins were the carriers of ______.
nucleus, cytoplasm, genetic information
The Search for the Chemical Nature
of Genes: DNA or Protein?
In ______, ______, ______, and ______, researchers at the ______ in New York, published experiments showing that DNA was the carrier of genetic information in bacteria. This evidence, though clear-cut, failed to convince many influential scientists.
1944, Oswald Avery, Colin MacLeod, Maclyn McCarty, Rockefeller Institute
The Search for the Chemical Nature
of Genes: DNA or Protein?
Additional evidence for the role of DNA as a carrier of genetic information came from ______ and ______ who worked with viruses. This evidence that DNA carries genetic information, along with other research over the next few years, provided solid proof that ______, not protein, is the genetic material, setting the stage for work to establish the structure of DNA.
Hershey, Chase, DNA
Once it was accepted that DNA carries genetic information, efforts were focused on deciphering the structure of the DNA molecule and the mechanism by which information stored in it produces a ______.
phenotype
The Structure of DNA and RNA
One of the great discoveries of the twentieth century was made in ______ by ______ and ______, who described the structure of DNA.
1953, James Watson, Francis Crick
The Structure of DNA and RNA
______ is a long, ladder-like macromolecule that twists to form a double helix. Each linear strand of the helix is made up of subunits called ______.
DNA, nucleotides
The Structure of DNA and RNA
In DNA, there are four different nucleotides, each of which contains a ______, abbreviated ______, ______, ______, or ______. These four bases, in various sequence combinations, ultimately encode ______.
nitrogenous base, A (adenine), G (guanine), T (thymine), C (cytosine), genetic information
The Structure of DNA and RNA
The two strands of DNA are exact complements of one another, so that the rungs of the ladder in the double helix always consist of ______ and ______ base pairs.
A=T, G=C
The Structure of DNA and RNA
Along with ______, ______ and ______ were awarded a Nobel Prize in ______ for their work on the structure of DNA.
Maurice Wilkins, Watson, Crick, 1962
The Structure of DNA and RNA
Another nucleic acid, ______, is chemically similar to DNA but contains a different sugar (______ rather than deoxyribose) in its nucleotides and contains the nitrogenous base ______ in place of thymine.
RNA, ribose, uracil
The Structure of DNA and RNA
______, however, is generally a single-stranded molecule.
RNA
Gene Expression: From DNA to Phenotype
The genetic information encoded in the order of nucleotides in DNA is expressed in a series of steps that results in the formation of a functional gene product. In the majority of cases, this product is a ______.
protein
Gene Expression: From DNA to Phenotype
In eukaryotic cells, the process leading to protein production begins in the nucleus with ______, in which the nucleotide sequence in one strand of DNA is used to construct a ______. Once an RNA molecule is produced, it moves to the ______, where the RNA— called ______, or ______ for short—binds to a ribosome. The synthesis of proteins under the direction of mRNA is called ______.
transcription, complementary RNA sequence, cytoplasm, messenger RNA, mRNA, translation
Gene Expression: From DNA to Phenotype
The information encoded in mRNA (called the ______) consists of a linear series of nucleotide triplets. Each triplet, called a ______, is complementary to the information stored in DNA and specifies the insertion of a specific ______ into a ______.
genetic code, codon, amino acid, protein
Gene Expression: From DNA to Phenotype
______ are polymers made up of amino acid monomers.
Proteins
Gene Expression: From DNA to Phenotype
There are ______ different amino acids commonly found in proteins.
20
Gene Expression: From DNA to Phenotype
Protein assembly is accomplished with the aid of adapter molecules called ______.
transfer RNA (tRNA)
Gene Expression: From DNA to Phenotype
Within the ribosome, ______ recognize the information encoded in the mRNA codons and carry the proper ______ for construction of the protein during ______.
tRNAs, amino acids, translation
Proteins and Biological Function
In most cases, ______ are the end products of gene expression.
proteins
Proteins and Biological Function
The diversity of proteins and the biological functions they perform—the diversity of life itself—arises from the fact that proteins are made from combinations of ______ different amino acids.
20
Proteins and Biological Function
Consider that a protein chain containing 100 amino acids can have at each position any one of 20 amino acids; the number of possible different 100-amino-acid proteins, each with a unique sequence, is therefore equal to ______.
Proteins and Biological Function
Obviously, ______ are molecules with the potential for enormous structural diversity and serve as the mainstay of biological systems.
proteins
Proteins and Biological Function
______ form the largest category of proteins. These molecules serve as biological catalysts, lowering the energy of activation in reactions and allowing cellular metabolism to proceed at body temperature.
Enzymes
Proteins and Biological Function
Proteins other than enzymes are critical components of cells and organisms. These include ______, the oxygen-binding molecule in red blood cells; ______, a pancreatic hormone; ______, a connective tissue molecule; and ______ and ______, the contractile muscle proteins.
hemoglobin, insulin, collagen, actin, myosin
Proteins and Biological Function
A protein’s shape and chemical behavior are determined by its ______ sequence of ______, which in turn is dictated by the stored information in the ______ of a ______ that is transferred to ______, which then directs the protein’s synthesis.
linear, amino acids, DNA, gene, RNA
Linking Genotype to Phenotype:
Sickle-Cell Anemia
Once a protein is made, its biochemical or structural properties play a role in producing a ______.
phenotype
Linking Genotype to Phenotype:
Sickle-Cell Anemia
When ______ alters a gene, it may modify or even eliminate the encoded protein’s usual function and cause an altered phenotype. To trace this chain of events, we will examine sickle-cell anemia, a human genetic disorder.
mutation
Linking Genotype to Phenotype:
Sickle-Cell Anemia
______ is caused by a mutant form of hemoglobin, the protein that transports oxygen from the lungs to cells in the body.
Sickle-cell anemia
Linking Genotype to Phenotype:
Sickle-Cell Anemia
Hemoglobin is a composite molecule made up of two different proteins, ______ and ______, each encoded by a different gene.
α-globin, β-globin
Linking Genotype to Phenotype:
Sickle-Cell Anemia
In sickle-cell anemia, a mutation in the gene encoding ______ causes an amino acid substitution in 1 of the ______ amino acids in the protein.
β-globin, 146
Linking Genotype to Phenotype:
Sickle-Cell Anemia
Figure 1.9 shows the DNA sequence, the corresponding mRNA codons, and the amino acids occupying positions 4–7 for the normal and mutant forms of β-globin. Notice that the mutation in sickle-cell anemia consists of a change in one DNA nucleotide, which leads to a change in codon ______ in mRNA from ______ to ______, which in turn changes amino acid number 6 in β-globin from ______ to ______. The other ______ amino acids in the protein are not changed by this mutation.
6, GAG, GUG, glutamic acid, valine, 145
Linking Genotype to Phenotype:
Sickle-Cell Anemia
Individuals with two mutant copies of the ______ gene have sickle-cell anemia.
β-globin
Linking Genotype to Phenotype:
Sickle-Cell Anemia
Their mutant β-globin proteins cause hemoglobin molecules in red blood cells to ______ when the blood’s oxygen concentration is ______, forming long chains of hemoglobin that distort the shape of ______. The deformed cells are fragile and break easily, reducing the number of red blood cells in circulation (______ is an insufficiency of red blood cells).
polymerize, low, red blood cells, anemia
Linking Genotype to Phenotype:
Sickle-Cell Anemia
Sickle-shaped blood cells block blood flow in ______ and ______, causing severe pain and damage to the heart, brain, muscles, and kidneys.
capillaries, small blood vessels
Linking Genotype to Phenotype:
Sickle-Cell Anemia
All the symptoms of this disorder are caused by a change in a single nucleotide in a gene that changes one amino acid out of ______ in the ______ molecule, demonstrating the close relationship between genotype and phenotype.
146, β-globin
The era of recombinant DNA began in the early ______, when researchers discovered that ______, used by bacteria to cut and inactivate the DNA of invading viruses, could be used to cut any organism’s DNA at specific nucleotide sequences, producing a reproducible set of fragments.
1970s, restriction enzymes
Soon after, researchers discovered ways to insert the DNA fragments produced by the action of ______ into carrier DNA molecules called ______ to form recombinant DNA molecules.
restriction enzymes, vectors
When transferred into bacterial cells, thousands of copies, or ______, of the combined vector and DNA fragments are produced during ______. Large amounts of cloned DNA fragments can be isolated from these bacterial host cells. These DNA fragments can be used to isolate genes, to study their organization and expression, and to study their nucleotide sequence and evolution.
clones, bacterial reproduction
Collections of clones that represent an organism’s ______, defined as the complete haploid DNA content of a specific organism, are called ______. Genomic libraries are now available for hundreds of species.
genome, genomic libraries
______ has not only accelerated the pace of research but also given rise to the biotechnology industry, which has grown to become a major contributor to the U.S. economy.
Recombinant DNA technology
The use of recombinant DNA technology and other molecular techniques to make products is called ______.
biotechnology
In the United States, ______ has quietly revolutionized many aspects of everyday life; products made by biotechnology are now found in the supermarket, in health care, in agriculture, and in the court system.
biotechnology
Plants, Animals, and the Food Supply
The use of ______ to genetically modify crop plants has revolutionized agriculture. Genes for traits including resistance to herbicides, insects, and genes for nutritional enhancement have been introduced into crop plants.
recombinant DNA technology
Plants, Animals, and the Food Supply
The transfer of heritable traits across species using recombinant DNA technology creates ______.
transgenic organisms
Plants, Animals, and the Food Supply
Herbicide-resistant ______ and ______ were first planted in the mid-______, and transgenic strains now represent about ______ percent of the U.S. corn crop and ______ percent of the U.S. soybean crop.
corn, soybeans, 1990s, 88, 93
Plants, Animals, and the Food Supply
It is estimated that more than ______ percent of the processed food in the United States contains ingredients from transgenic crops.
70
Plants, Animals, and the Food Supply
New methods of cloning livestock such as ______ and ______ have also changed the way we use these animals. In ______, ______ the sheep was cloned by ______, a method in which the nucleus of an adult cell is transferred into an egg that has had its nucleus removed. This method makes it possible to produce dozens or hundreds of genetically identical offspring with desirable traits and has many applications in agriculture, sports, and medicine.
sheep, cattle, 1996, Dolly, nuclear transfer
Plants, Animals, and the Food Supply
Biotechnology has also changed the way human proteins for medical use are produced. Through use of ______, transgenic animals now synthesize these therapeutic proteins.
gene transfer
Plants, Animals, and the Food Supply
In ______, an anticlotting protein derived from the milk of ______ was approved by the U.S. Food and Drug Administration for use in the United States. Other human proteins from transgenic animals are now being used in clinical trials to treat several diseases. The biotechnology revolution will continue to expand as new methods are developed to make an increasing array of products.
2009, transgenic goats
Biotechnology in Genetics and Medicine
More than ______ children or adults in the United States suffer from some form of genetic disorder, and every child-bearing couple faces an approximately ______ percent risk of having a child with a genetic anomaly. The molecular basis for hundreds of genetic disorders is now known, and many of these genes have been ______, ______, and ______.
10 million, 3, mapped, isolated, cloned
Biotechnology in Genetics and Medicine
Biotechnology-derived genetic testing is now available to perform ______ of heritable disorders and to test parents for their status as “______” of more than ______ inherited disorders.
prenatal diagnosis, carriers, 100
Biotechnology in Genetics and Medicine
Newer methods now under development offer the possibility of scanning an entire ______ to establish an individual’s risk of developing a genetic disorder or having an affected child. The use of ______ and related technologies raises ethical concerns that have yet to be resolved.
genome, genetic testing
The use of recombinant DNA technology to create ______ prompted scientists to consider sequencing all the clones in a library to derive the nucleotide sequence of an organism’s genome. This sequence information would be used to identify each gene in the genome and establish its function.
genomic libraries
One such project, the ______, began in ______ as an international effort to sequence the human genome.
Human Genome Project, 1990
By ______, the publicly funded ______ and a private, industry-funded genome project completed sequencing of the gene-containing portion of the genome.
2003, Human Genome Project
As more genome sequences were acquired, several new biological disciplines arose. One, called ______ (the study of genomes), studies the structure, function, and evolution of genes and genomes. A second field, ______, identifies the set of proteins present in a cell under a given set of conditions, and studies their functions and interactions.
genomics, proteomics
To store, retrieve, and analyze the massive amount of data generated by genomics and proteomics, a specialized subfield of information technology called ______ was created to develop hardware and software for processing nucleotide and protein data.
bioinformatics
Geneticists and other biologists now use information in databases containing ______ sequences, ______ sequences, and ______ networks to answer experimental questions in a matter of minutes instead of months and years. A feature called “Exploring Genomics,” located at the end of many of the chapters in this textbook, gives you the opportunity to explore these databases for yourself while completing an interactive genetics exercise.
nucleic acid, protein, gene-interaction
Modern Approaches to Understanding Gene Function
Historically, an approach referred to as ______ or ______ was essential for studying and understanding gene function. In this approach geneticists relied on the use of ______ mutations or ______ mutations (using chemicals, X-rays or UV light as examples) to cause altered phenotypes in model organisms, and then worked through the lab-intensive and time- consuming process of identifying the genes that caused these new phenotypes. Such characterization often led to the identification of the gene or genes of interest, and once the technology advanced, the gene sequence could be determined.
classical, forward genetics, naturally occurring, intentionally induced
Modern Approaches to Understanding Gene Function
______ approaches are still used, but as whole genome sequencing has become routine, molecular approaches to understanding gene function have changed considerably in genetic research. These modern approaches are what we will highlight in this feature.
Classical genetics
Modern Approaches to Understanding Gene Function
For the past two decades or so, geneticists have relied on the use of molecular techniques incorporating an approach referred to as ______.
reverse genetics
Modern Approaches to Understanding Gene Function
In ______, the DNA sequence for a particular gene of interest is known, but the role and function of the gene are typically not well understood. For example, molecular biology techniques such as ______ render targeted genes non-functional in a model organism or in cultured cells, allowing scientists to investigate the fundamental question of “what happens if this gene is disrupted?” After making a knock-out organism, scientists look for both apparent ______ changes, as well as those at the ______ and ______ level. The ultimate goal is to determine the ______ of the gene.
reverse genetics, gene knockout, phenotype, cellular, molecular, function
After the rediscovery of ______’s work in 1900, research using a wide range of organisms confirmed that the principles of inheritance he described were of universal significance among plants and animals. Geneticists gradually came to focus attention on a small number of organisms, including the fruit fly (______) and the mouse (______). This trend developed for two main reasons: first, it was clear that genetic mechanisms were the same in most organisms, and second, these organisms had characteristics that made them especially suitable for genetic research. They were easy to grow, had relatively short life cycles, produced many offspring, and their genetic analysis was fairly straightforward. Over time, researchers created a large catalog of mutant strains for these species, and the mutations were carefully studied, characterized, and mapped. Because of their well-characterized genetics, these species became ______, defined as organisms used for the study of basic biological processes.
Mendel, Drosophila melanogaster, Mus musculus, model organisms
The Modern Set of Genetic Model Organisms
Gradually, geneticists added other species to their collection of model organisms: ______ (such as the ______ and ______) and ______ (the bacterium ______ and the yeast ______).
viruses, T phages, lambda phage, microorganisms, Escherichia coli, Saccharomyces cerevisiae
The Modern Set of Genetic Model Organisms
More recently, additional species have been developed as model organisms, three of which are shown in the chapter opening photograph. Each species was chosen to allow study of some aspect of embryonic development. The nematode ______ was chosen as a model system to study the development and function of the nervous system because its nervous system contains only a few hundred cells and the developmental fate of these and all other cells in the body has been mapped out.
Caenorhabditis elegans
The Modern Set of Genetic Model Organisms
______, a small plant with a short life cycle, has become a model organism for the study of many aspects of plant biology. The ______, ______, is used to study vertebrate development: it is small, it reproduces rapidly, and its egg, embryo, and larvae are all ______.
Arabidopsis thaliana, zebrafish, Danio rerio, transparent
Model Organisms and Human Diseases
The development of recombinant DNA technology and the results of genome sequencing have confirmed that all life has a common ______. Because of this, genes with similar functions in different organisms tend to be similar or identical in ______ and ______. Much of what scientists learn by studying the genetics of model organisms can therefore be applied to humans as the basis for understanding and treating human diseases.
origin, structure, nucleotide sequence
Model Organisms and Human Diseases
In addition, the ability to create ______ by transferring genes between species has enabled scientists to develop models of human diseases in organisms ranging from bacteria to fungi, plants, and animals
transgenic organisms
Model Organisms and Human Diseases
The idea of studying a human disease such as colon cancer by using ______ may strike you as strange, but the basic steps of ______ (a process that is defective in some forms of colon cancer) are the same in both organisms, and a gene involved in DNA repair (______ in E. coli and ______ in humans) is found in both organisms. More importantly, E. coli has the advantage of being easier to grow (the cells divide every ______), and researchers can easily create and study new mutations in the bacterial mutL gene in order to figure out how it works. This knowledge may eventually lead to the development of drugs and other therapies to treat colon cancer in humans.
E. coli, DNA repair, mutL, MLH1, 20 minutes
Model Organisms and Human Diseases
The fruit fly, ______, is also being used to study a number of human diseases. Mutant genes have been identified in D. melanogaster that produce phenotypes with structural abnormalities of the ______ and ______ of the nervous system. The information from genome-sequencing projects indicates that almost all these genes have human counterparts. For example, genes involved in a complex human disease of the retina called ______ are identical to Drosophila genes involved in ______. Study of these mutations in Drosophila is helping to dissect this complex disease and identify the function of the genes involved.
Drosophila melanogaster, nervous system, adult-onset degeneration, retinitis pigmentosa, retinal degeneration
Model Organisms and Human Diseases
Another approach to studying diseases of the human nervous system is to transfer ______ genes into Drosophila using recombinant DNA technology. The transgenic flies are then used for studying the mutant human genes themselves, other genes that affect the expression of the human disease genes, and the effects of therapeutic drugs on the action of those genes—all studies that are difficult or impossible to perform in humans. This gene transfer approach is being used to study almost a dozen human neurodegenerative disorders, including ______, ______, ______, and ______.
mutant human disease, Huntington disease, Machado–Joseph disease, myotonic dystrophy, Alzheimer disease
Model Organisms Used to Study Some Human Diseases
E. coli
______
Colon cancer and other cancers
Model Organisms Used to Study Some Human Diseases
S. cerevisiae
______
Cancer, Werner syndrome
Model Organisms Used to Study Some Human Diseases
D. melanogaster
______
Disorders of the nervous system, cancer
Model Organisms Used to Study Some Human Diseases
C. elegans
______
Diabetes
Model Organisms Used to Study Some Human Diseases
D. rerio
______
Cardiovascular disease
Model Organisms Used to Study Some Human Diseases
M. musculus
______
Lesch–Nyhan disease, cystic fibrosis, fragile-X syndrome, and many other diseases
Mendel described his decade-long project on inheritance in pea plants in an ______ paper presented at a meeting of the ______ in ______. Less than 100 years later, the ______ Nobel Prize was awarded to ______, ______, and ______ for their work on the structure of DNA. This time span encompassed the years leading up to the acceptance of Mendel’s work, the discovery that genes are on ______, the experiments that proved ______ encodes genetic information, and the elucidation of the molecular basis for DNA replication. The rapid development of genetics from Mendel’s monastery garden to the Human Genome Project and beyond is summarized in a timeline in Figure 1.15.
1865, Natural History Society of Brünn, Moravia, 1962, James Watson, Francis Crick, Maurice Wilkins, chromosomes, DNA
The Nobel Prize and Genetics
No other scientific discipline has experienced the explosion of information and the level of excitement generated by the discoveries in ______. This impact is especially apparent in the list of Nobel Prizes related to genetics, beginning with those awarded in the early and mid-twentieth century and continuing into the present. Nobel Prizes in Medicine or Physiology and Chemistry have been consistently awarded for work in genetics and related fields.
genetics
The Nobel Prize and Genetics
One of the first such prizes awarded was given to ______ in ______ for his research on the chromosome theory of inheritance. That award was followed by many others, including prizes for the discovery of genetic recombination, the relationship between genes and proteins, the structure of DNA, and the genetic code. This trend has continued throughout the twentieth and twenty-first centuries. The advent of genomic studies and the applications of such find- ings will most certainly lead the way for future awards.
Thomas H. Morgan, 1933
What year?
Mendel’s work published
1860s
What year?
Mendel’s work rediscovered, correlated with chromosome behavior in meiosis
1900s
What year?
Chromosome theory of inheritance proposed. Transmission genetics evolved
1900s-1940s
What year?
DNA shown to carry genetic information. Watson-Crick model of DNA
1940s-1950s
What year?
Era of molecular genetics. Gene expression, regulation understood
1950s-1960s
What year?
Recombinant DNA technology developed. DNA cloning begins
1970s-1980s
What year?
Genomics begins. Human Genome Project initiated
1990s
What year?
Application of genomics begins
2000s
