Chapter 1:

The Science of Genetics

The Basic Terms of Genetics
» Genetics – is the branch of biology that studies heredity and variation.
» Heredity – the transmission of traits from one generation to another, from parents to offspring.
» Variation – any difference existing between individuals of the same species.
» Gene - is the basic physical and functional unit of heredity. Genes are made up of DNA.
» Chromosome - a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying
genetic information in the form of genes.
» Genome - the complete set of genes or genetic material present in a cell or organism.
» Deoxyribonucleic acid - is the hereditary material in humans and almost all other organisms.
» Allele - is a variant form of a given gene.
» Phenotype - the set of observable characteristics of an individual resulting from the interaction of its genotype with the
environment.
» Genotype - is the set of genes in our DNA which is responsible for a particular trait.
» Mutation - is the alteration of the nucleotide sequence of the genome of an organism, virus, or extra chromosomal DNA.
» Homozygous - is a word that refers to a particular gene that has identical alleles.
» Heterozygous - refers to having inherited different forms of a particular gene from each parent.
» Dominant Trait – is an inherited characteristic that appears in an offspring if it is contributed from a parent through a
dominant allele.
» Recessive Trait - is a trait that is expressed when an organism has two recessive alleles, or forms of a gene. » Gene
Expression - is the process by which information from a gene is used in the synthesis of a functional gene product.
The Three Great Milestones in Genetics
1. Mendel: Genes and the Rule of Inheritance
» Gregor Mendel, known as the "father of modern genetics," was born in Austria in 1822.
» A monk, Mendel discovered the basic principles of heredity through experiments in his monastery's garden.
» His experiments showed that the inheritance of certain traits in pea plants follows particular patterns, subsequently
becoming the foundation of modern genetics and leading to the study of heredity.
» He chose to work with the garden pea
WHY GARDEN PEA?
» They grow quickly
» They reproduce by self-pollination. This means that the pea flowers have both female and male parts
» They also possess characteristics that can easily be recognized like height, color of flowers, and shapes of seeds »
Pollination could be controlled in this group of plants with minimum work. This meant that he could develop plants that
always produce seeds with the same traits » Garden peas could also produce enough offspring to conduct a study.
2. Watson and Crick: The Structure of DNA
» The structure of DNA, as represented in Watson and Crick's model, is a double-stranded, antiparallel, right-handed helix.
» The sugar-phosphate backbones of the DNA strands make up the outside of the helix, while the nitrogenous bases are
found on the inside and form hydrogen-bonded pairs that hold the DNA strands together.
3. The Human Genome Sequencing:
Sequencing DNA and Cataloguing Genes
» The Human Genome Project (HGP) refers to the international 13-year effort, formally begun in October 1990 and
completed in 2003, to discover all the estimated 20,000 to 25,000 human genes and make them accessible for further
biological study.
» Another project goal was to determine the complete sequence of the 3 billion DNA subunits (bases in the human
genome).
» The Human Genome Project was a landmark global scientific effort whose signature goal was to generate the first
sequence of the human genome.
» In 2003, the Human Genome Project produced a genome sequence that accounted for over 90% of the human genome.
DNA as a Genetic Material
» In all cellular organisms, the genetic material is DNA. » This material must be able to replicate so that copies can be
transmitted from cell to cell and from parents to offspring;
» it must contain information to direct cellular activities and to guide the development, functioning, and behavior of
organisms;
» and it must be able to change so that over time, groups of organisms can adapt to different circumstances.
DNA REPLICATION
» Deoxyribonucleic acid, commonly known as DNA, is a nucleic acid that has three main components: a deoxyribose sugar,
a phosphate, and a nitrogenous base.
» Since DNA contains the genetic material for an organism, it is important that it be copied when a cell divides into
daughter cells. The process that copies DNA is called replication.
» Replication involves the production of identical helices of DNA from one double-stranded molecule of DNA.
» Enzymes are vital to DNA replication since they catalyze very important steps in the process. » The overall DNA replication
process is extremely important for both cell growth and reproduction in organisms. It is also vital in the cell repair process.
STEPS OF DNA REPLICATION
» Step 1: Replication Fork Formation
» Step 2: Primer Binding
» Step 3: Elongation
» Step 4: Termination
REPLICATION ENZYMES
» DNA helicase - It forms the replication fork by breaking hydrogen bonds between nucleotide pairs in DNA.
» DNA primase - a type of RNA polymerase that generates RNA primers. Primers are short RNA molecules that act as
templates for the starting point of DNA replication.
» DNA polymerases - synthesize new DNA molecules by adding nucleotides to leading and lagging DNA strands.
» Topoisomerase or DNA Gyrase - unwinds and rewinds DNA strands to prevent the DNA from becoming tangled or
supercoiled. » Exonucleases - group of enzymes that remove nucleotide bases from the end of a DNA chain.
» DNA ligase - joins DNA fragments together by forming phosphodiester bonds between nucleotides.
GENE EXPRESSION: USING GENETIC INFORMATION
» Protein synthesis – transcription and translation
» In eukaryotic cells, transcription takes place in the nucleus. During transcription, DNA is used as a template to make a
molecule of messenger RNA (mRNA). The molecule of mRNA then leaves the nucleus and goes to a ribosome in the
cytoplasm, where translation occurs.
» During translation, the genetic code in mRNA is read and used to make a polypeptide. These two processes are summed
up by the central dogma of molecular biology: DNA → RNA → Protein.
TRANSCRIPTION:
1. Initiation is the beginning of transcription. It occurs when the enzyme RNA polymerase binds to a region of a gene called
the promoter. This signals the DNA to unwind so the enzyme can “read” the bases in one of the DNA strands. The enzyme is
ready to make a strand of mRNA with a complementary sequence of bases.
2. Elongation is the addition of nucleotides to the mRNA strand.
3. Termination is the ending of transcription. The mRNA strand is complete, and it detaches from DNA
Processing mRNA:
» In eukaryotes, the new mRNA is not yet ready for translation.
» At this stage, it is called pre-mRNA, and it must go through more processing before it leaves the nucleus as mature mRNA.
» The processing may include splicing, editing, and polyadenylation.
» These processes modify the mRNA in various ways.
» Such modifications allow a single gene to be used to make more than one protein.
TRANSLATION
» Translation is the second part of the central dogma of molecular biology: RNA → Protein. » It is the process in which the
genetic code in mRNA is read to make a protein.
» After mRNA leaves the nucleus, it moves to a ribosome, which consists of rRNA and proteins.
» The ribosome reads the sequence of codons in mRNA, and molecules of tRNA bring amino acids to the ribosome in the
correct sequence.
» When there is a changes in the structure of genetic materials in DNA sequence that may or may not be inherited is called
mutation.
» Mutation is caused by some induced factors such as high-energy radiation, toxic chemicals, extreme temperature, and
radioactive substances knows as mutagens.
» When mutation affects the body cells, this is somatic mutation. They do not affect the offspring. Only the mutant gene of
the body is affected.
» Gametic mutation, it can be inherited by the next generation since the affected are the gametes.
» Mutation could be:
1. Point Mutation
2. Frameshift Mutation
3. Chromosomal Mutation
1. POINT MUTATION
» This type of mutation will cause a change in an amino acid in a polypeptide chain.
A. Silent Mutation – A nucleotide is substituted but still the same amino acids is produces
Normal Sequence: ACU CCA GAG - CCA (Lysine)
Silent Mutation: ACU CCC GAG - CCC (Lysine)
» This type of mutation will cause a change in an amino acid in a polypeptide chain.
B. Missense Mutation – A nucleotide is substituted by and results to different codon that corresponds to different amino
acids Normal Sequence: ACU CCA GAC - GAC (Aspartic Acid) Missense Mutation: ACU CCA GCC - GCC (Alanine)
» This type of mutation will cause a change in an amino acid in a polypeptide chain.
C. Nonsense Mutation – A nucleotide is substituted and results to the formation of stop codon instead of a codon in coding
an amino acids. Normal Sequence: ACU CCA AAA - AAA (Lysine) Nonsense Mutation: ACU CCA UAA - UAA (STOP)
2. FRAMESHIFT MUTATION
» This is type of mutation affects only one nitrogen base by either being completely deleted or extra one is inserted into the
middle of the sequence of DNA.
A. Insertion – A single nitrogenous base is added in the middle of the sequence so that wrong amino acid is translated and
alters the protein. Normal Sequence: CAG UCC ACU -Glu Ser Thr Insertion Mutation: ACU GUC CAC U -Glu Val His ?
» This is type of mutation affects only one nitrogen base by either being completely deleted or extra one is inserted into the
middle of the sequence of DNA.
B. Deletion – A nitrogenous bases is deleted or taken out of the sequence of amino acids. Normal Sequence: CAG UCC ACU -
Glu Ser Thr Insertion Mutation: ACU CCA CU -Glu Pro ?
3. CHROMOSOMAL MUTATION
» Alteration or error which cause change in the structure or number of chromosomes.
A. Deletion – A portion of a chromosome is omitted and genes are lost permanently. Example is Cri-du chat or the “cats cry
syndrome” which is the deletion on the short arm of chromosome 5.
B. Insertion –A portion of a chromosome is added to another chromosome.
C. Inversion – in order of genes in the chromosome is reversed.
D. Duplication –A portion of the chromosome is repeated and doubled in the same chromosome. Example is Down
Syndrome having an extra copy of Chromosome 21 (Trisomy 21)
E. Translocation – the chromosome segments change positions.
BRANCHES OF GENETICS
CLASSICAL GENETICS
» Classical genetics is the branch of genetics based solely on visible results of reproductive acts. » It is the oldest discipline in
the field of genetics, going back to the experiments on Mendelian inheritance by Gregor Mendel who made it possible to
identify the basic mechanisms of heredity.
» Concerned with genes, mutation and phenotypes.
» Begins with the arrangement of genes on the chromosome and their transmission to the next generation through
meiosis, the methods that generate mutations and identify mutants, and the various patterns of inheritance to produce a
specific trait or phenotype
MOLECULAR GENETICS
» Molecular Genetics is the study of the structures, replication, and expression of the genetic material and of the expressed
protein
» It includes the methods involved in manipulating the expression and analysis of the genetic material. » Molecular genetics
is the field of biology that studies the structure and function of genes at a molecular level and thus employs methods of
both molecular biology and genetics.
» The study of chromosomes and gene expression of an organism can give insight into heredity, genetic variation, and
mutations.
EVOLUTIONARY GENETICS
» Population and Evolutionary Genetics is the study of the mechanism that result in changes in allele frequencies in
populations over time and the consequences of those changes.
» It is the broad field of studies that resulted from the integration of genetics and Darwinian evolution » Evolutionary
genetics is the study of how genetic variation leads to evolutionary change. It includes topics such as the evolution of
genome structure, the genetic basis of speciation and adaptation, and genetic change in response to selection within
populations.
APPLIED GENETICS
» Animal Husbandry – concerned with animals that are raises for meat, fibre, milk, milk, eggs, or other products.
» Plant Breeding – purposeful manipulation of plant species in order to create desired genotypes and phenotypes for
specific purpose.
» Epidemiological Genetics – study of the role of genetic factors in determining health and diseases in families and in
population.
» Medical Genetics – involve the diagnosis and management of hereditary disorders.
» Amniocentesis – the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for
developmental abnormalities in a fetus.
» Genetic Counseling – it provides information and support to people who have, or may be at risk for genetic disorder.
» Genetic Engineering – is the direct manipulation of an organisms’ gene using biotechnology.
» Developmental Genetics – is the study of how genes control the growth and development of an organism throughout its
life cycle.
» Recombinant DNA Technique – is the joining together of DNA molecules from two different species.

Chapter 2
Mendel and the Gene Idea
Overview: Drawing from the Deck of Genes
• What genetic principles account for the passing of traits from parents to offspring?
• The “blending” hypothesis is the idea that genetic material from the two parents blends together (like blue and yellow
paint blend to make green)
• The “particulate” hypothesis is the idea that parents pass on discrete heritable units (genes)
• This hypothesis can explain the reappearance of traits after several generations
• Mendel documented a particulate mechanism through his experiments with garden peas
Mendel used the scientific approach to identify two laws of inheritance
• Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned experiments
Mendel’s Experimental, Quantitative Approach
• Advantages of pea plants for genetic study – There are many varieties with distinct heritable features, or characters (such
as flower color); character variants (such as purple or white flowers) are called traits
– Mating can be controlled
– Each flower has sperm-producing organs (stamens) and egg-producing organ (carpel) – Cross-pollination (fertilization
between different plants) involves dusting one plant with pollen from another
• Mendel chose to track only those characters that occurred in two distinct alternative forms • He also used varieties that
were true-breeding (plants that produce offspring of the same variety when they self-pollinate)
• In a typical experiment, Mendel mated two contrasting, true-breeding varieties, a process called hybridization
• The true-breeding parents are the P generation
• The hybrid offspring of the P generation are called the F1generation
• When F1 individuals self-pollinate or cross pollinate with other F1 hybrids, the F2 generation is produced
The Law of Segregation
• When Mendel crossed contrasting, true breeding white- and purple-flowered pea plants, all of the F1 hybrids were purple
• When Mendel crossed the F1hybrids, many of the F2plants had purple flowers, but some had white
• Mendel discovered a ratio of about three to one, purple to white flowers, in the F2 generation
• Mendel reasoned that only the purple flower factor was affecting flower color in the F1 hybrids • Mendel called the
purple flower color a dominant trait and the white flower color a recessive trait • The factor for white flowers was not
diluted or destroyed because it reappeared in the F2 generation
• Mendel observed the same pattern of inheritance in six other pea plant characters, each represented by two traits
• What Mendel called a “heritable factor” is what we now call a gene
Mendel’s Model
• Mendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2 offspring
• Four related concepts make up this model • These concepts can be related to what we now know about genes and
chromosomes
• First: alternative versions of genes account for variations in inherited characters
• For example, the gene for flower color in pea plants exists in two versions, one for purple flowers and the other for white
flowers
• These alternative versions of a gene are now called alleles
• Each gene resides at a specific locus on a specific chromosome
• Second: for each character, an organism inherits two alleles, one from each parent
• Mendel made this deduction without knowing about the role of chromosomes
• The two alleles at a particular locus may be identical, as in the true-breeding plants of Mendel’s P generation
• Alternatively, the two alleles at a locus may differ, as in the F1 hybrids
• Third: if the two alleles at a locus differ, then one (the dominant allele) determines the organism’s appearance, and the
other (the recessive allele) has no noticeable effect on appearance
• In the flower-color example, the F1 plants had purple flowers because the allele for that trait is dominant
• Fourth: (now known as the law of segregation): the two alleles for a heritable character separate (segregate) during
gamete formation and end up in different gametes
• Thus, an egg or a sperm gets only one of the two alleles that are present in the organism
• This segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis
• Mendel’s segregation model accounts for the 3:1 ratio he observed in the F2 generation of his numerous crosses
• The possible combinations of sperm and egg can be shown using a Punnett square, a diagram for predicting the results of
a genetic cross between individuals of known genetic makeup
• A capital letter represents a dominant allele, and a lowercase letter represents a recessive allele
Useful Genetic Vocabulary
• An organism with two identical alleles for a character is said to be homozygous for the gene controlling that character
• An organism that has two different alleles for a gene is said to be heterozygous for the gene controlling that character
• Unlike homozygotes, heterozygotes are not true-breeding
• Because of the different effects of dominant and recessive alleles, an organism’s traits do not always reveal its genetic
composition
• Therefore, we distinguish between an organism’s phenotype, or physical appearance, and its genotype, or genetic
makeup
• In the example of flower color in pea plants, PP and Pp plants have the same phenotype (purple) but different genotypes
The Testcross
• How can we tell the genotype of an individual with the dominant phenotype?
• Such an individual could be either homozygous dominant or heterozygous
• The answer is to carry out a testcross: breeding the mystery individual with a homozygous recessive individual
• If any offspring display the recessive phenotype, the mystery parent must be heterozygous
The Law of Independent Assortment
• Mendel derived the law of segregation by following a single character
• The F1 offspring produced in this cross were monohybrids, individuals that are heterozygous for one character
• A cross between such heterozygotes is called a monohybrid cross
• Mendel identified his second law of inheritance by following two characters at the same time
• Crossing two true-breeding parents differing in two characters produces dihybrids in the F1 generation, heterozygous for
both characters • A dihybrid cross, a cross between F1 dihybrids, can determine whether two characters are transmitted to
offspring as a package or independently
• Using a dihybrid cross, Mendel developed the law of independent assortment
• The law of independent assortment states that each pair of alleles segregates independently of each other pair of alleles
during gamete formation
• Strictly speaking, this law applies only to genes on different, nonhomologous chromosomes or those far apart on the
same chromosome
• Genes located near each other on the same chromosome tend to be inherited together
Inheritance patterns are often more complex than predicted by simple Mendelian genetics
• The relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied
• Many heritable characters are not determined by only one gene with two alleles
• However, the basic principles of segregation and independent assortment apply even to more complex patterns of
inheritance
 Chapter 3
Non-Mendelian Genetics
Extending Mendelian Genetics for a Single Gene
• Inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations:
– When alleles are not completely dominant or recessive
– When a gene has more than two alleles
– When a gene produces multiple phenotypes © 2011 Pearson Education, Inc.
Degrees of Dominance
• Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical
• In incomplete dominance, the phenotype of F1 hybrids is somewhere between the phenotypes of the two parental
varieties
• In codominance, two dominant alleles affect the phenotype in separate, distinguishable ways
The Relation Between Dominance and Phenotype
• A dominant allele does not subdue a recessive allele; alleles don’t interact that way
• Alleles are simply variations in a gene’s nucleotide sequence
• For any character, dominance/recessiveness relationships of alleles depend on the level at which we examine the
phenotype
• Tay-Sachs disease is fatal; a dysfunctional enzyme causes an accumulation of lipids in the brain
– At the organismal level, the allele is recessive
– At the biochemical level, the phenotype (i.e., the enzyme activity level) is incompletely dominant
– At the molecular level, the alleles are
codominant
Multiple Alleles
• Most genes exist in populations in more than two allelic forms
• For example, the four phenotypes of the ABO blood group in humans are determined by three alleles for the enzyme (I)
that attaches A or B carbohydrates to red blood cells: IA, IB, and i.
• The enzyme encoded by the IA allele adds the A carbohydrate, whereas the enzyme encoded by the IB allele adds the B
carbohydrate; the enzyme encoded by the i allele adds neither
Pleiotropy
• Most genes have multiple phenotypic effects, a property called pleiotropy
• For example, pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases, such as cystic
fibrosis and sickle-cell disease
Extending Mendelian Genetics for Two or More Genes
• Some traits may be determined by two or more genes
Epistasis
• In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus
• For example, in Labrador retrievers and many other mammals, coat color depends on two genes
• One gene determines the pigment color (with alleles B for black and b for brown)
• The other gene (with alleles C for color and c for no color) determines whether the pigment will be deposited in the hair
Polygenic Inheritance
• Quantitative characters are those that vary in the population along a continuum
• Quantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single
phenotype
• Skin color in humans is an example of polygenic inheritance
Nature and Nurture: The Environmental Impact on Phenotype
• Another departure from Mendelian genetics arises when the phenotype for a character depends on environment as well
as genotype
• The norm of reaction is the phenotypic range of a genotype influenced by the environment • For example, hydrangea
flowers of the same genotype range from blue-violet to pink, depending on soil acidity
• Norms of reaction are generally broadest for polygenic characters
• Such characters are called multifactorial because genetic and environmental factors collectively influence phenotype
Integrating a Mendelian View of Heredity and Variation
• An organism’s phenotype includes its physical appearance, internal anatomy, physiology, and behavior
• An organism’s phenotype reflects its overall genotype and unique environmental history
Pedigree Analysis
• A pedigree is a family tree that describes the interrelationships of parents and children across generations
• Inheritance patterns of particular traits can be traced and described using pedigrees
Recessively Inherited Disorders
• Many genetic disorders are inherited in a recessive manner
• These range from relatively mild to life threatening
The Behavior of Recessive Alleles
• Recessively inherited disorders show up only in individuals homozygous for the allele
• Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal; most individuals with
recessive disorders are born to carrier parents
• Albinism is a recessive condition characterized by a lack of pigmentation in skin and hair
• If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low
• Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of
the same rare allele
• Most societies and cultures have laws or taboos against marriages between close relatives
Cystic Fibrosis
• Cystic fibrosis is the most common lethal genetic disease in the United States,striking one out of every 2,500 people of
European descent
• The cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes leading to a
buildup of chloride ions outside the cell
• Symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small intestine
Sickle-Cell Disease: A Genetic Disorder with Evolutionary Implications
• Sickle-cell disease affects one out of 400 African-Americans
• The disease is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells
• In homozygous individuals, all hemoglobin is abnormal (sickle-cell)
• Symptoms include physical weakness, pain, organ damage, and even paralysis
• Heterozygotes (said to have sickle-cell trait) are usually healthy but may suffer some symptoms
• About one out of ten African Americans has sickle cell trait, an unusually high frequency of an allele with detrimental
effects in homozygotes
• Heterozygotes are less susceptible to the malaria parasite, so there is an advantage to being heterozygous .
Dominantly Inherited Disorders
• Some human disorders are caused by dominant alleles
• Dominant alleles that cause a lethal disease are rare and arise by mutation
• Achondroplasia is a form of dwarfism caused by a rare dominant allele
Huntington’s Disease: A Late-Onset Lethal Disease
• The timing of onset of a disease significantly affects its inheritance
• Huntington’s disease is a degenerative disease of the nervous system
• The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age • Once the deterioration
of the nervous system begins the condition is irreversible and fatal
Multifactorial Disorders
• Many diseases, such as heart disease, diabetes, alcoholism, mental illnesses, and cancer have both genetic and
environmental components
• Little is understood about the genetic contribution to most multifactorial diseases