Chapter 2:
● Macromolecules
○ Large cellular polymers assembled by chemically linking monomers together
■ Carbohydrates
● sugars
○ ex. glucose
■ Lipids
● fats & oils
○ ex. cholesterol
■ Proteins
● amino acid chains folded together in 3D-shape
○ ex. collagen, enzymes
■ Nucleic Acid
● nucleotide monomers
○ two types → DNA & RNA
○ ATP is also a nucleic acid
Cell Structure Reflects Functions:
● Cellular domains
○ Plasma membrane
■ double-layered membrane made of hydrophilic and hydrophobic lipids
■ separates cell from external environment
■ responsible for exchange of material from outside environment
■ passive (no energy required) vs. active transport (ATP required)
○
Cytoplasm
■ Nucleus
● contains genetic information necessary for cell structure and
function
● enclosed by envelope
● contains chromatin which will later condense to form
chromosomes
○ chromatin are the DNA and protein components of
chromosomes, visible as threads in nuclei
○ chromosomes are the threadlike structures in the
nucleus that carry genetic information
■ Nucleolus
● produces ribosomes
● located in nucleus
■ Rough Endoplasmic Reticulum (RER)
● site of protein synthesis for intracellular & extracellular use
■ Smooth ER
● involved in phospholipid production
■ Ribosomes
● aids in production of proteins on the RER
■ Golgi Complex
● sorts, chemically modifies,and packages proteins produced in
the RER
■
■
■
○
Secretory vesicles
● stores protein hormones or enzymes in cytoplasm waiting for
signal to release
Lysosome
● cellular digestion
Mitochondria
● completes breakdown of glucose
● cellular respiration that produces ATP (energy)
Cystic Fibrosis
■ genetic disorder
■ functional defect in a membrane protein that controls movement of
chloride ions across membrane
● causes accumulation of thick mucus in lungs and organ ducts
● can cause premature death
The Cell Cycle: Vocab
● Autosomes
○ chromosomes other than sex chromosomes chromosome 1 - 22
● Sex chromosomes
○ the X and Y chromosomes associated with sex determination
● Cell cycle
○ sequence of events that takes place between successive mitotic divisions
● Centromere
○ region of a chromosome to which spindle fibers attach during cell division.
There are different locations of a centromere
● Sister chromatids
○ two chromatids joined by a common centromere, and each chromatid carries
identical Genetic information
● G0 phase
○ when cells leave cell cycle and are inactive
The Cell Cycle:
● Interphase
○ cells spend longest amount of time in this phase of the cell cycle
■ G1 stage
● begins immediately after mitosis
● RNA, proteins, and organelles are synthesized,
■ S phase
● DNA is replicated and chromosomes form sister chromatids
■ G2 phase
● Mitochondria divide and precursors of spindle fibers are
synthesized
●
Mitosis
○ Prophase
■ chromosomes condense and nuclear envelope disappears
○
○
○
●
■ centrioles divide and migrate to opposite ends of cell
■ spindle fibers form and attach to chromosomes
Metaphase
■ chromosomes line up in middle of dividing cell
Anaphase
■ chromosomes begin to separate
Telophase
■ chromosomes reach opposite poles
■ new nuclear envelope forms
■ chromosomes decondense
Cytokinesis
○ cleavage furrow forms and deepens and the cytoplasm divides
Cell Division by Meiosis:
● same as with mitosis, but goes through another set of phases to end up with 4
daughter cells
● Interphase → Mitosis → Cytokinesis → Meiosis I complete
Vocab:
● Meiosis
○ process of cell division during which replication produces 4 daughter cells,
aka two successive cell divisions occur
● Diploid (2n)
○ each chromosome is represented twice as a member of a homologous pair
● Haploid (n)
○ each chromosome is represented once in an unpaired condition
● Homologous chromosomes
○ chromosomes that physically associate during meiosis and have identical
gene loci
● Assortment
○ result of meiosis that puts random combinations of maternal and paternal
chromosomes into gametes
● Crossing over
○ process in which chromosomes physically exchange parts
● Allele
○ one of the possible alternative forms of a gene (distinguished through
phenotypic effects)
●
Meiosis II
○ Prophase II
■ chromosomes recoil and shorten
○ Metaphase II
■ unpaired chromosomes become aligned at equator of cell
○ Anaphase II
■ centromeres separate and sister chromatids pull apart
○ Telophase II
■
chromosomes uncoil and nuclear envelope reforms (meiosis ends) →
Cytokinesis
Formation of Gametes:
Vocab:
● Spermatogonia
○ mitotically active cells in the gonads of males that give rise to primary
spermatocytes
● Spermatids
○ four haploid cells produced by meiotic division of a primary spermatocyte
● Oogonia
○ cells that produce primary oocytes by mitotic division
● Primary oocytes
○ cell produced from oogonia that will begin meiosis during embryogenesis
● Secondary oocyte
○ large cell produced by first meiotic division
● Ovum
○ haploid cell produced by meiosis that becomes a functional gamete (only
completes meiosis II if fertilized by sperm)
● Polar bodies
○ cells produced in the first and second meiotic division in female meiosis that
contain little cytoplasm and don’t function as gametes
Chapter 3:
Inheritance of traits:
● Gregor Mendel used planned experiments using pea plants to study inheritance traits
● Mendel’s results
■ Only one of the parental traits was present in the F1 plants
■ The trait not present in the F1 plants reappeared in about 25% of the
F2 plants
■ In all crosses, it did not matter which trait was present in the plant that
contributed the pollen → the results were always the same
Mendel’s Laws:
● Principle of Segregation (1st law)
○ The separation of members of a gene pair from each other during gamete
formation
● Principle of Independent Assortment (2nd law)
○ The random distribution of genes into gametes during meiosis
Vocab:
● Gene
○ fundamental unit of heredity
● Genetics
○ the scientific study of heredity
●
●
●
●
●
●
●
●
●
●
●
●
Dominant trait
○ expressed in F1 generation
Recessive trait
○ trait unexpressed in F1, but reappeared in some members of F2 generation
Phenotype
○ observable properties of an organism
Genotype
○ specific genetic constitution of an organism
Homozygous
○ carrying two same alleles for one or more genes
Heterozygous
○ carrying two different alleles for one or more genes
Locus
○ position occupied by a gene on a chromosome
Pedigree
○ diagram listing the members and ancestral relationships in a family
Incomplete Dominance
○ expression of a phenotype that is intermediate to those of the parents
Codominace
○ full phenotypic expression of both members of a gene pair in the
heterozygous condition
Proband
○ first affected family member who seeks medical attention for a genetic
disorder
Epistasis
○ interaction of two or more non-allelic genes to control a single phenotype
Chapter 4:
Pedigree Analysis is a Basic Method in Human Genetics:
● Important because
○ used to predict genetic risk to a fetus
○ the risk of someone developing an adult-onset disorder
○ risk for having an affected child in the future
Five Basic Patterns of Mendelian Inheritance:
● Autosomal recessive
○ characteristics
■ for rare traits, affected individuals have unaffected parents
■ all the children of two affected homozygous parents are affected
■ for two heterozygotes, the risk of having an unaffected child is 75%
and the risk of having an affected child is 25%
● Ex. albinism, cystic fibrosis
● Autosomal Dominant
○ characteristics
■ unless a new mutation is involved, every affected individual has at
least one affected parent
■
●
●
●
because most affected individuals are heterozygotes with a
homozygous recessive spouse, each child has a 50% chance of being
affected
■ because the trait is autosomal, the numbers of affected males and
females are equal
■ two affected individuals may have two unaffected children
■ the phenotype in homozygous dominant individuals is often more
severe than the heterozygous phenotype
● Ex. Marfan Syndrome (affects skeletal system, eyes, and
cardiovascular system)
X-linked Dominant
○ only small number of dominant traits are carried on X chromosome
○ characteristics
■ affected males transmit the trait to all their daughters but none of their
sons
■ a heterozygous affected female will transmit the trait to half of her
children, with sons and daughters affected equally
■ twice as many females are affected as males
X-linked Recessive
○ characteristics
■ Hemizygous males and homozygous females are affected
■ X-linked recessive conditions are much more common in males than
in females
■ In the case of rare alleles, males are almost always affected
■ Affected males who receive the mutant allele from their mothers
transmit it to all of their daughters, but not to their sons
■ Daughters of affected males are heterozygous and therefore
unaffected, but sons of heterozygous females have a 50% chance
each of being affected
● Ex. Color blindness, muscular dystrophy
Y-linked
○ characteristics
■ all genes on Y chromosome are passed directly from father to son
■ all Y-linked traits are expressed because males are hemizygous for all
genes
Non-Mendelian Inheritance:
● Genetic disorders caused by mutations in mitochondrial genes have the following
properties
○ They are all maternally inherited and produce a distinctive pattern of
inheritance
○ All the children of affected females are affected
○ All affected females will transmit the disorder to all their offspring, but affected
males cannot transmit the mutations to any of their children
○ Disorders that follow non-mendelian inheritance mainly affect muscles and
are called mitochondrial myopathies
Many Factors can Affect the Outcome of Pedigree Analysis:
●
●
Phenotypes are often age related
○ Ex. Huntington's disease (neural degeneration & dementia)
Penetrance and expressivity cause variations in phenotypes
○ Penetrance
■ probability that a disease phenotype will appear when a
disease-related genotype is present
○ Expressivity
■ the range of phenotypes resulting from a given genotype
■ analysis of pedigrees is subject to many factors that can influence
interpretation
Chapter 5:
Phenotypes can be discontinuous or continuous:
●
●
Discontinuous variation
○ phenotypes that fall into two or more distinct, non overlapping classes
Continuous variation
○ a distribution of phenotypic characters that is distributed from one extreme to
another in an overlapping manner
Vocab:
● Complex traits
○ traits controlled by multiple genes, the interaction of genes with each other
and with environmental factors
■ characteristics
● Traits are usually quantified by measurement rather than by
counting
● Two or more genes contribute to the phenotype and each gene
contributes to the phenotype, but the effect of individual genes
may be small
● Environmental factors interact with the genotype to produce
the phenotype
● Follow a bell-shaped curve
● Polygenic traits
○ traits controlled by two or more genes
● Multifactorial traits
○ traits that result from the interaction of one or more environmental factors and
two or more genes
■ as the number of loci that controls a trait increases, the number of
phenotypic classes increases, and as the number of phenotypes
increases, the phenotypic difference between each class decreases
The Additive Model for Complex Traits:
● Effects of each gene are added together
○ characteristics
■ Trait is controlled by three genes, each of which has two alleles
■
■
■
■
Each dominant allele makes an equal contribution to the phenotype,
and recessive alleles make no contribution
The effect of each active allele on the phenotype is small and additive
The genes controlling the trait are not linked, they assort
independently
The environment acts equally on all genotypes
Averaging out the Phenotype:
● Regression to the Mean
○ the tendency of offspring of parents with extreme differences in phenotype to
exhibit a phenotype that is the average of the two parental phenotypes
Multifactorial Traits:
● The genotype represents the genetic constitution of an individual and is fixed at the
moment of fertilization
● The phenotype is the sum of the observable characteristics and it is variable and
undergoes continuous change throughout the life of the organism
● The environment in which a gene exists and operates includes all other genes in the
genotype and their effects and interactions, as well as non genetic factors, can
interact with the genotype
Vocab:
● Epigenetics
○ reversible chemical modifications of chromosomal DNA and/or associated
histone proteins that change the pattern of gene expression without affecting
the nucleotide sequence of the DNA
Threshold model to study complex traits:
● environmental conditions are most likely to have the greatest impact on those
individuals who have the highest level of genetic predisposition
● The risk for a disorder should decrease as the degree of relatedness decreases
○ In complex threshold disorders the risk of recurrence depends on several
factors
■ consanguinity → high level of relatedness
■ previous affected child → if parents have two affected kids their
genotype may be close to threshold for recurrence
■ severity of defect → a severely affected phenotype means the the
affected child’s genotype is well over the threshold and that the
parents’ genotype confer a higher recurrence risk
■ higher frequency in one sex → if complex trait is expressed more
often in one sex compared to the other than threshold for that specific
sex is then higher/lower
Heritability Measures the Genetic Contribution to Phenotypic Variation:
Vocab:
● Genetic variance
○
●
●
●
phenotypic variance of a trait in a population that is attributed to genotypic
differences
Environmental variance
○ phenotypic variation of a trait in a population that is attributed to differences in
the environment
Heritability
○ expression of how much of the observed variation in a phenotype is due to
differences in genotype
Concordance rate in twin studies
○ agreement between traits exhibited by both twins
Chapter 6:
The human Chromosome Set:
Chromosomes have four important parts:
● Centromere
○ region of a chromosome where spindle fibers attach during cell division,
which gives a chromosome its characteristic shape
■ divides regions into two arms
● metacentric
○ centrally placed centromere
● submetacentric
○ centromere located closer to one end of the
chromosome than the other
● acrocentric
○ centromere placed very close to, but not at, one end
● One short arm
○ also known as p arm
● One long arm
○ also known as q arm
● Telomeres
○ short repeated DNA sequences located at each end of chromosomes
A chromosome’s address:
● each arm is subdivided into numbered regions from the centromere to the telomere
○ Address of a chromosome includes
■ the chromosome (1-23)
■ the arm
■ the region
■ the band
Making a Karyotype:
● Karyotype
○ complete set of chromosomes from a cell that has been photographed during
cell division (in metaphase) and arranged in a standard sequence
■
can be constructed from several cell types
● blood cells
● skin cells
● amniotic fluid
● placental cells
Analyzing Karyotypes:
● A karyotype provides several kinds of information
○ the number of chromosomes present
○ the number and type of sex chromosomes
○ the presence or absence of individual chromosomes
○ the nature and extent of detectable structural abnormalities
■ chromosome painting used to differentiate and recognize karyotypes
easier
Methods of retrieving DNA for Karyotyping prenatally:
● Amniocentesis
○ sampling of fluid surrounding the developing fetus by inserting a hollow
needle and withdrawing suspended fetal cells and fluid, which is then used in
diagnosing fetal genetic and developmental disorders
■ risk for miscarriage is high with this method
● Chorionic Villus Sampling
○ sampling of fetal chorionic cells by inserting a catheter through vagina or
abdominal wall into the uterus, which is used to diagnose biochemical and
cytogenetic defects in the embryo
■ can be performed early on in pregnancy (8-9 weeks)
● Non-Invasive Prenatal Diagnosis
○ Testing of fetal cells isolated from mother’s blood and isolating and testing
free fetal DNA (ffDNA) present in mother’s blood
Variations in Chromosome Number:
Vocab:
● Polyploidy
○ chromosome number that is a multiple of the normal haploid chromosome set
● Aneuploidy
○ chromosome number that is not an exact multiple of the haploid set
● Monosomy
○ condition where one member of a chromosomal pair is missing (having one
less than the diploid number (2n - 1)
● Trisomy
○ condition where one chromosome is present in three copies, whereas all
others are diploid (2n + 1)
Polyploidy Changes the Number of Chromosomal Sets:
● Abnormalities can arise in several ways
○ errors in meiosis during gamete formation
○ errors in mitosis after fertilization
■
●
●
if homologous chromosomes fail to separate during meiosis I, the
division in meiosis II will produce diploid gametes
Triploidy
○ chromosomal number that is three times the haploid number, having three
copies of all autosomes and three sex chromosomes
■ 1% of all conceptions are triploid, but 99% result in miscarriage
■ triploid newborns die within the first month and have an enlarged
head, fused fingers and toes, and malformations of the mouth, eyes,
and genitals
Tetraploidy
○ chromosomal number that is four times the haploid number, having four
copies of all autosomes and four sex chromosomes
■ can result from failure of cytokinesis in meiosis I
■ tetraploidy is found in 5% of all miscarriages
■ tetraploidy has at least two different causes
● errors in cell division
● accidents at fertilization
Aneuploidy changes the number of individual chromosomes:
● Most common cause of aneuploidy is nondisjunction
○ Nondisjunction
■ failure of homologous chromosomes to separate properly during
meiosis or mitosis
● if this occurs in meiosis I, all gametes will be abnormal and
carry either both members of a chromosomal pair or neither
● if this occurs in meiosis II, it produces 50% normal haploid
cells, and 50% abnormal cells, one with an extra copy of a
chromosome and one missing a chromosome
Autosomal Trisomy is a lethal condition:
● Autosomal monosomic embryos are lost very early, before pregnancy is recognized
Autosomal Trisomy is Common:
● Only a few autosomal trisomies result in live births as 50% of the others are
miscarriages
○ Trisomy 21
■ extra copy of chromosomes 21, results in Down Syndrome
■ distinctive skin fold known as epicanthic fold
■ 40% of all kids with trisomy 21 have congenital heart defects
○ Trisomy 13
■ Patau Syndrome
■ lethal condition
■ includes facial malformations, eye defects, extra fingers, and feet with
large protruding heels
■ parental age is only factor known to be related to trisomy 13 (parents
of children with trisomy 13 have an average age of 32)
○ Trisomy 18
■ Edwards Syndrome
■
■
■
■
small at birth and grow very slowly
intellectual disabilities
80% of these births are female
parental age is risk factor in trisomy 18
Sex Chromosome Aneuploidy:
● Sex chromosome anomalies in live births is 1 in 400 for males and 1 in 650 for
females (monosomy and trisomy)
○ Turner Syndrome
■ monosomy of the X chromosome that results in female sterility
○ Klinefelter Syndrome
■ Aneuploidy of the sex chromosomes involving an XXY chromosomal
constitutions
● 60% result from maternal nondisjunction
● other forms of this syndrome have increased risks for severe
symptoms, and intellectual disability
○ XXY Syndrome
■ many males with this karyotype are imprisoned for antisocial behavior
(violence)
Structural Changes Within and Between Chromosomes:
● Deletions
○ deletion of a chromosome region causes developmental abnormalities
○ deletion of an entire chromosome is lethal
■ Cri du Chat Syndrome
● deletion of the short arm of chromosome 5 associated with an
array of congenital malformations (infant cry that sounds like
meowing cat most characteristic)
● Translocations
○ translocations move one part of a chromosome to another, nonhomologous
chromosome
■ there are two types of translocation
● reciprocal translocation
○ two nonhomologous chromosomes exchange parts
○ no genetic information is gained or lost, but genes are
moved to new chromosomal locations
● robertsonian translocation
○ can produce genetically unbalanced gametes with
duplicated or deleted chromosomal segments, resulting
in embryonic death or abnormal offspring
● Uniparental Disomy
○ condition where both copies of a chromosome are inherited from one parent
■ ex. Prader-Willi-Syndrome
● Copy number variations
○ changes in the number of copies of chromosomal DNA segments and the
genes they contain
■ A DNA segment at least 1000 base pairs long with a variable copy
number in the gamete
●
●
diseases associated with CNV
○ Lupus, Alzheimer's, HIV/AIDS
Fragile Sites
○ appear as gaps or breaks at specific sites on a chromosome and are inherited
as codominant traits
■ Fragile X Syndrome
● an X chromosome carries a gap or break, at band q27 and is
associated with intellectual disability in males
Chapter 7:
The Human Reproductive System:
vocab
● Zygote
○ fertilized egg that develops into new human
Male System:
vocab
● Sperm
○ male gamete
● Gonads
○ organs where gametes are produced
● Testes
○ male gonads that produce spermatozoa and sex hormones
○ produce sperm and sex steroids
● Scrotum
○ pouch of skin outside of male body that contains testes
○ provides proper temperature for sperm formation
● Seminiferous tubules
○ small tightly coiled tubules inside testes where sperm are produced
● Spermatogenesis (starts at puberty and each cycle is 48 days long)
○ process of sperm production
● Spermatocytes
○ diploid cells that undergo meiosis to form haploid spermatids
● Epididymis
○ part of male reproductive system where sperm are stored
○ site of sperm maturation
● Vas deferens
○ duct connected to epididymis, through which sperm travels
○ conducts sperm to urethra
● Ejaculatory duct
○ short connector from the vas deferens to the urethra
● Urethra
○ tube that passes from the bladder and opens to the outside
○ functions in urine and sperm transport
● Seminal vesicles
○ glands in males that secrete fructose and prostaglandins into the semen
○ produce seminal fluid that nourishes sperm
● Prostaglandins
○
locally acting chemical messengers that stimulate contraction of the female
reproductive system to assist in sperm movement
● Bulbourethral glands
○ gland that secretes a mucus-like substance that provides lubrication for
intercourse
● Semen
○ mixture of sperm and other secretions
Female System:
vocab
● Oocyte
○ cell from which an ovum develops by meiosis
● Ovaries
○ female gonads that produce oocytes and female sex hormones
○ produce ova (eggs)
● Follicle
○ developing egg surrounded by an outer layer of follicle cells, contained in the
ovary
● Ovulation
○ release of secondary oocyte from the follicle (once a month)
● Uterus
○ hollow pear-shaped muscular organ where an early embryo will implant and
develop
○ nourishes and protects embryo and fetus
● Oviduct
○ duct with fingerlike projections surrounding the ovary and connecting to the
uterus (fallopian tube)
○ transports sperm to ova / transports fertilized ova to uterus
● Endometrium
○ inner lining of the uterus that is shed if fertilization has not occurred
● Cervix
○ lower neck of the uterus opening into the vagina
● Vagina
○ opening that receives the penis during intercourse + is the birth canal
○ receptacle for sperm
● Oogenesis (begins during embryogenesis and lasts 12-50 years)
○ process of oocyte production
● Oogonia
○ cells that produce primary oocytes by mitotic division
A Survey of Human Development from Fertilization to Birth:
vocab
● Fertilization
○ fusion of two gametes to produce a zygote
● Blastocyst
○ developmental stage at which the embryo implants into the uterine wall
● Trophoblast
○ outer layer of cells in the blastocyst that gives rise to the membranes
surrounding the embryo
●
●
Inner cell mass
○ cluster of cells in the blastocyst that gives rise to the embryonic body
(contains the embryonic stem cells)
Chorion
○ two-layered structure formed during embryonic development from the
trophoblast
Defining Sex in Stages:
● Development is divided into three trimesters:
○ each trimester lasts between 12-13 weeks
■ First trimester
● organ formation
○ almost all important events vital to human development
occur in the first trimester
■ Second trimester
● skeleton forms and heartbeat can be heard
○ develops finger and toenails and can open its eyes
■ Third trimester
● rapid growth of all developed organs and of the fetus itself
● two months before birth the fetus doubles in size
○ fetus is about 50 cm and weighs 2.5 kg
■ Birth
● hormonally induced
● cervix softens
● hormone oxytocin stimulates uterine contractions
○ fetus and placenta are delivered
Teratogens Are a Risk to the Developing Fetus:
● Teratogen
○ any physical or chemical agent that brings about an increase in congenital
malformations
■ radiation, viruses, and chemicals are all teratogens
■ early stages of pregnancy are the most vulnerable to teratogens (2-18
weeks)
■ alcohol, drugs and certain foods can also be teratogens and effect
fetal development
● Fetal alcohol syndrome (FAS)
○ constellation of birth defects caused by maternal alcohol consumption during
pregnancy
■ can result in miscarriage, growth retardation, facial abnormalities,
intellectual disabilities, and learning disabilities
How is Sex Determined?
vocab
● Sex ratio
○ proportion of males and females, which changes throughout the life cycle
○ the ratio is 1:1 at fertilization, but the ratio of females to males increases as a
population ages
●
●
Environmental interactions help determine sex
○ in some animal species higher temperatures produce females and lower
temperatures produce males, and in other species the opposite is true
Chromosomes help determine sex
○ some females have only one x chromosome
○ some males have more than one X chromosome
○ anyone with a Y chromosome is almost always male no matter the number of
X chromosomes
■ outcome of developing as either male/female despite typical XX, XY
chromosomes depends on the distribution and expression of genes on
the X and Y chromosomes and the interactions between genes with
many environmental factors
■ chromosomal sex of an individual may differ from their phenotypic sex
(intersex)
● sex can be defined at several levels
○ chromosomal sex
○ gonadal sex
○ phenotypic sex
Hormones Help Shape Male & Female Phenotypes:
vocab
● SRY
○ sex determining region of the Y chromosome located near the short arm that
plays a major role in causing the undifferentiated gonad to develop into testes
● Testosterone
○ steroid hormone produced by the testes
● Anti-Müllerian Hormone (AMH)
○ hormone produced by the developing testis that causes the breakdown of the
Müllerian ducts in the embryo
Mutations can Uncouple Chromosomal Sex from Phenotypic Sex:
● Complete androgen insensitivity
○ X-linked genetic trait that causes XY individuals to develop into phenotypic
females
● Gonadal intersexuality
○ individuals have both male and female structures at different times of their life
■ early stages of life → phenotypic sex does not match chromosomal
sex
■ later stages of life → phenotypic and chromosomal sex align
Equalizing the Expression of X Chromosomes Genes in Males and Females:
vocab
● Barr body
○ densely straining mass in the somatic nuclei of mammalian females (an
inactivated X chromosome)
● Dosage compensation
○ mechanism that regulates the expression of sex-linked genes
● Lyon hypothesis
○
●
proposal that dosage compensation in mammalian females is accomplished
by partially and randomly inactivating one of the two X chromosomes
X inactivation center
○ region on the X chromosome where inactivation begins
Sex Influenced Traits:
● Sex influenced traits
○ traits controlled by autosomal genes that are usually dominant in one sex but
recessive in the other sex
■ these traits are expressed differently in males vs. females
● Sex-limited genes
○ loci that produces a phenotype in only one sex
Chapter 8:
DNA is the Carrier of Genetic Information
● Chemist Friedrich Miescher (1860s)
○ first to isolate and purify a cellular organelle
■ transcription
● process of transferring genetic information between cells by
DNA molecules
■ transforming factor
● the molecular agent of transformation; DNA
○ Experiment S-cells and R-cells
■ findings
● DNA carries genetic information. Only DNA transfers heritable
information from one bacterial strain to another
● DNA controls synthesis of specific products. Transfer of DNA
from strain S to strain R transfers the ability to synthesize a
specific gene product
The Chemistry of DNA
● Matter is composed of atoms
● elements
○ different types of atoms
● molecules
○ atoms combine to form molecules
● covalent bonds
○ atoms in molecules are bonded together by chemical links
○ simplest form of covalent bond shares a pair of electrons
● hydrogen bond
○ weak attraction
○ carry partial but opposite electrical charges
● Nucleotides are the building blocks of nucleic acid
○ two nucleic acids
■
○
○
○
○
DNA
●
found in nucleus and mitochondria
RNA
■
found in nucleus and cytoplasm
● four bases
A,G,U,C
Nucleotides have three components
■ A nitrogen containing base
● two types of bases
● purines
○ adanine
○ guanine
● pyrimidines
○ thymine
○ cytosine
○ uracil
■ only in RNA
■ A sugar
● ribose
○ found in RNA
○ extra OH group
● deoxyribose
○ found in DNA
■ A phosphate group
● strongly acidic
● compound containing phosphorus and chemically bonded to
four oxygen molecules
A nucleotide is linked together by covalent bonds
polynucleotides
■ multiple nucleotides linked together by covalent bonds
The Watson-Crick Model of DNA Structure
● discovery of DNA model was historic
● paved the way for scientists to understand cellular processes
● gave rise to molecular biology
● genetic engineering
● genomics
● gene testing
● James Watson & Francis Crick (1950s)
○ worked on finding the molecular structure of DNA
they used
■ X-ray diffraction studies
■ Chemical analysis of DNA base composition
● in images they found DNA had a helical shape and constant
diameter
●
●
●
●
phosphates were on the outside of the helix
bases were on the inside of the helix
genetic information is stored in the sequence of bases in the
DNA
○ model offers molecular explanation for mutation
○ the complementary sequence of bases in the two
strands explains how DNA is copied before each cell
division
Erwin Chargaff
○ analyzed base composition of DNA
■ his model contained the following
● equal amount of Adenine and Thymine
● equal amount of guanine and cytosine
● DNA is composed of two polynucleotide chains
● the chains run in opposite directions (antiparallel)
● two polynucleotide chains are coiled to form a double helix
● sugar and phosphate are on the outside
● bases are inside paired with hydrogen bonds
● base pairing is highly specific
● predictable base pairing makes two polynucleotide chains of
DNA complementary
RNA is a Single-Stranded Nucleic Acid
transfers genetic information from nucleus to cytoplasm
● participates in synthesis of proteins
● component of ribosomes
● participates in regulation of gene expression
○ Most RNA is single-stranded, however RNA molecules can fold back on
themselves forming short double-strands
DNA Replication Depends on Complementary Base Pairing
complex, multistep process
● takes place during S-phase
● begins at sites along the chromosomes called origins of replication
○ process
■ double helix is unwound → enzyme DNA polymerase reads nucleotide
sequence → any incorrect base pairs are removed in reading of newly
synthesized sequence → short strands are sealed by enzyme DNA
ligase to form continuous strand → proteins wind the template to form
a double helix
The Organization of DNA in Chromosomes
● Spatial arrangement of DNA in the nucleus plays a key role in regulating the
expression of genetic information
○ chromatin
■ each chromosome consists of a double-stranded DNA molecule
combined with proteins
■
○
○
chromatin folds into loops and fibers at higher level of organization, up
to chromosomal level
Histones
■ major class of proteins in chromatin
■ plays role in chromosome structure and gene regulation
nucleosomes
■ DNA wound around a core of histone molecules
■ small spherical bodies
Chapter 9:
The Link Between Genes and Proteins
● Archibald Garrod
○ first to propose direct link between genes and proteins
○ proposed relationship between genes, proteins, and phenotypes studying
condition called:
■ alkaptonuria
● autosomal recessive trait where urine goes black when
exposed to oxygen
● George Beadle and Edward Tatum
○ genes produce phenotypes through the action of proteins
■ phenotype of a cell, tissue, and organism are the result of protein
function
● mutant phenotype → genetic disorder
● genetic information encoded in the sequence of nucleotides in
DNA
● proteins are composed of amino acids linked together by
chemical bonds
○ amino acid made of
amino group, carboxyl group, R group
■ there are 20 different amino acids that can
combine in billions of different ways to
synthesize billions of different proteins
The Genetic Code: The Key to Life
● Linear sequence of nucleotides in a gene encodes the information that spells out the
linear sequence of amino acids in a protein
○ 3 nucleotides carry information for 1 amino acid
○ some amino acids could be specified by more than one combination of 3
nucleotides
● Codon
○ triplets of nucleotides in mRNA that encode the information for a specific
amino acid in a protein
● Stop codon
○ a codon in mRNA that signals the end of translation (e.g., UAA, UAG, UGA)
● Start codon
○
condon present in mRNA that signals the location for translation to begin
(e.g., AUG is a start codon and codes for amino acid, methionine)
■ is always the first codon in the RNA
Tracing the Flow of Genetic Information from Nucleus to Cytoplasm
Transfer of genetic information into a linear sequence of amino acids occurs in a series of
steps:
● Information encoded in a gene is copied to pre-messenger RNA
○ this process is called transcription
● Pre-mRNA is processed into a finished mRNA and moves into the cytoplasm through
a nuclear pore
● In cytoplasm the information encoded in mRNA is converted into the sequence of
amino acids in a polypeptide chain, and are then folded to form a protein
○ this process is called translation
● Type and order of amino acids in amino acid chain determines structural and
functional characteristics of the protein, and plays a role in phenotypic expression
Transcription Produes Genetic Messages
● Initiation
○ RNA polymerase binds to promoter that marks the beginning of a gene
● Elongation
○ strands of DNA unwind further and polymerase reads the nucleotides
sequence from the template strand and inserts/links together complementary
RNA nucleotides
● Termination
○ RNA polymerase eventually reaches end of gene marked by nucleotides
called termination sequence and stops adding nucleotides to pre-mRNA
■ falls off DNA template
● DNA then re-form double helix
○ Messenger RNA is processed and spliced
● Vocab:
○ introns
■ DNA sequences present in some genes that are transcribed but are
removed during processing and therefore are not present in mature
mRnA
○ exons
■ DNA sequences that are transcribed, joined to other exons during
mRNA processing, and translated into amino acid sequence of a
protein
○ cap
■ modified base (guanine nucleotide) attached to the 5’ end of
eukaryotic mRNA molecules
○ poly-A tail
■ series of A nucleotides added to 3’ end of mRNA molecules
Translation Requires the Interaction of Several Components
● translation converts nucleotides sequence of mRNA into amino acid sequence of a
protein
○
○
●
each amino acid has three characteristic groups
■ R group
● an R group can be positively or negatively charged
■ Amino group
● chemical group found in amino acids and at one end of a
polypeptide chain
■ Carboxyl group
● chemical group found in amino acids and at one end of a
polypeptide chain
Essential amino acids
■ amino acids that cannot be synthesized by the body and must be
included in one's diet
● Messenger RNA, ribosomal RNA, and transfer RNA interact
during translation
Vocab:
○ Polypeptide
■ molecule made of amino acids joined together by peptide bonds
○ N-terminus
■ end of a polypeptide or protein that has a free amino group
○ C-terminus
■ end of a polypeptide or protein that has a free carboxyl group
○ Ribosomal RNA (rRNA)
■ RNA molecules that form part of the ribosome
○ Transfer RNA (tRNA)
■ small RNA molecule that contains a binding site for a specific type of
amino acid and has a three-base segment known as an anticodon that
recognizes a specific base sequence in messenger RNA
○ Anticodon
■ group of 3 nucleotides in a tRNA molecule that pairs with a
complementary sequence in an mRNA molecule
○ Polysomes
■ messenger RNA molecule with several ribosomes attached
○ Initiation complex
■ formed by the combination of mRNA, tRNA, and the small ribosomal
subunit (first step in translation)
○ Peptide bond
■ covalent chemical link between the carboxyl group of one amino acid
and the amino group of another amino acid
● Translation produces polypeptides from information in mRNA
○ Initiation
■ mRNA binds to small ribosomal subunit and the anticodon of initiator
tRNA carrying amino acid methionine pairs with AUG codon of mRNA
■ methionine is inserted first in all human proteins since AUG is the start
codon
■ initiation is complete when a large ribosomal subunit binds to the
complex
○ Elongation
■ amino acids are added to the growing polypeptide chain
■
○
rRNA act as an enzyme and forms peptide bonds between two amino
acids
Termination
■ occurs when ribosome reaches stop codon
■ proteins called release factors bind to stop codons
■ the polypeptide, mRNA, and tRNA are then released from the
ribosome
Polypeptides are Processed and Folded to Form Proteins
● Folding is often guided by proteins called chaperones
○ the 3-D shape of the processed protein is determined by its amino acid
sequence + chemical modifications
○ when released from the ribosome most polypeptides are processed, folded,
and converted into their functional form and become proteins
● Proteome
○ set of proteins present in a particular cell at a specific time under a particular
set of conditions
Protein Structure and Function are Related
● Four levels of protein structure
○ Primary structure
■ amino acid sequence in a polypeptide chain
○ Secondary structure
■ pleated or helical structure in a protein molecule generated by the
formation of bonds between amino acids
○ Tertiary structure
■ 3-D structure of a protein molecule brought about by folding on itself
○ Quaternary structure
■ structure formed by the interaction of two or more polypeptide chains
in a protein
● Misfolded proteins play a role in producing abnormal
phenotypes seen in several genetic disorders
○ prion
■ protein folded into an infectious conformation
that is the cause of several disorders
○ mad-cow disease
■ a prion disease of cattle, also known as BSE
Several Mechanisms Regulate the Expression of Genes
● Gene regulation
○ process of turning genes on and off
○ can occur at many steps during transcription, translation, and after translation
○ of these the most important step is regulation at the transcriptional level
○ Different ways of regulating gene expression
■ controlling access to the promoter region at the beginning of a gene
■ remodeling complexes chemically modifies histones, and DNA
partially unwinds from histone making a gene promoter accessible to
RNA polymerase
●
●
●
●
Chromatin remodeling
○ set of chemical changes to the DNA and histones that activate and inactivate
gene expression
○ most important way
Making changes to DNA instead of histones
○ gene silencing
○ addition of methyl groups to cytosine bases in the DNA of promoters turns
genes off
■ associated with several processes
● inactivation of X chromosome, cancer …
RNA interference (RNAi)
○ a mechanism of gene regulation that controls the amounts of mRNA available
for translation
Translational and Posttranslational Mechanisms Regulate the Production of Proteins
○ Poly-A tails are made longer → increased protein translation per mRNA
○ Poly-A tails are made shorter → decreases protein translation per mRNA
Chapter 10:
Vocab:
● Substrate
○ specific chemical compound that is acted on by an enzyme
● Product
○ specific chemical compound that is the result of enzymatic action. In
biochemical pathways, a compound can serve as the product of one reaction
and the substrate for the next reaction
● Metabolism
○ sum of all biochemical reactions by which cells convert and utilize energy
● Inborn error of metabolism
○ concept that many genetic traits result from alterations in biochemical
pathways
■ Phenylketonuria (PKU)
● an autosomal recessive disorder of amino acid metabolism
that results in intellectual disability if untreated
■ Galactosemia
● heritable trait associated with the inability to metabolize the
sugar galactose. If it is left untreated, high levels of
galactose-1-phosphate accumulate, causing cataracts and
intellectual disability
● Hemoglobin variants
○ alpha and beta globins with variant amino acid sequences
■ Thalassemias
● Disorders associated with an imbalance in the production of
alpha or beta globin
● Pharmacogenetics
○ branch of genetics concerned with the identification of protein variants that
underlie differences in the response to drugs
●
Ecogenetics
○ branch of genetics that studies genetic traits related to the response to
environmental substances
Chapter 11:
Mutations are heritable changes in DNA:
● Mutation
○ changes in the nucleotide sequence of DNA that can be passed onto future
generations
■ changes can occur in somatic cells (body cells) and/or germ cells
(reproductive cells)
● mutations can only passed on to future generations if the
mutations occur at the germ cell level
Mutations come in different forms:
● Can be a single nucleotide change in DNA
● A deletion or insertion of one/more base pairs
● An alteration in the structure of a chromosome
Detecting Mutations and measuring mutation rates:
● To determine whether an abnormal phenotype is causes by a genetic disorder,
geneticists depend on pedigree analysis
○ Measuring Mutation Rates
■ Mutation rate
■ number of events that produce mutated alleles per locus per
generation
● mutation rate is low, but can vary widely between
individuals/species
● two main methods of measuring mutation rates:
○ indirect method
■ infers mutation rates from levels of
genetic variation between/among
species
○ direct method
■ estimate the mutation rate of a specific
gene over a number of generations
● average mutation rate 1X10^-5
● mutation rates for nucleotide
base substitutions are much
lower
○
Some genes have higher/lower mutation rates, why?
■ Gene size
● the larger the gene, the more likely it is for mutations to
occur
○ Nucleotide sequence
○ trinucleotide repeats
■
■
form of mutation associated with the
expansion in copy number of a
nucleotide triplet in/near a gene
Mutagens
● physical or chemical agents that cause mutations
○ either spontaneously induced or by
environmental agents
Mutations can be Spontaneous or Induced:
● Errors in DNA replication cause spontaneous mutations
○ sometimes DNA polymerase inserts an incorrect base into a new strand of
DNA
■ if error isn’t corrected → mutation
● Chemical changes in bases can cause mutations
○ Tautomeric shifts
■ spontaneously occurring reversible shifts in purine/pyrimidine bases
that may result in mutation
■ hydrogen bonding properties of bases allow for non complementary
base pairing → mutation
○ Mutagens can cause mutations
■ some mutagens can directly change bases and base-pairing
properties in DNA by changing one base into another
● radiation
○ process by which electromagnetic energy travels
through space or air
● background radiation
○ radiation in environment that contributes to overall
radiation exposure
● rem
○ unit of radiation exposure used to measure radiation
damage in humans
■ process of radiation causing mutation
● radiation strikes molecules in cells → creates ions → ionized
molecules are highly reactive and can cause mutations
○ Chemicals can cause mutations
■ chemicals cause mutations in several ways
● nucleotide substitutions or change of number of nucleotides in
DNA
○ structural changes the bases in DNA causing a
base-pair change after replication
● base analogs
○ a purine or pyrimidine that differs in chemical structure
from those normally found in DNA or RNA
Mutations at the Molecular Level: DNA as a Target:
● Nucleotide substitutions
○ mutations that involve replacement of one or more nucleotides in a DNA
molecule with other nucleotides
■ alters sequence but not number of nucleotides
● Frameshift mutations
○ mutational events in which a number of bases are added to, or removed from
DNA causing a shift in the codon reading frame
■ frameshift mutations are caused by nucleotide deletions and insertions
■ change the number of nucleotides in a gene → large-scale changes to
amino acid sequence of a protein
● frameshift mutations account for 5-10% of all genetic disorders
● Missense mutations
○ mutations that cause the substitution of one amino acid for another in a
protein
■ can have variety of phenotypic effects
● some cause genetic disorders, others don’t
○ ex. hemoglobin mutations
● Sense mutations
○ mutations that change a termination codon into one that codes for an amino
acid → creates elongated proteins
● Nonsense mutations
○ mutations that change an amino acid specifying codon to one of the three
termination codons
■ UAA,UAG,UGA
○ Mutations can involve more than one nucleotide
■ allelic expression
● increase in gene size caused by expansions of the number of
repeats within a gene, converting a normal allele to a mutant
allele
○ many genetic disorders associated with expansion of
trinucleotide repeats
■ ex. fragile X syndrome
Mutations can be Repaired:
● Not all mutations are permanent
● All cells have repair systems that repair mutations and damage to DNA
○ human genome contains more than 175 genes devoted to DNA repair
○ rates of repair are close to levels of damage, which can overload repair
systems
■ cells that accumulate a lot of DNA damage can meet several fates:
● cells can become dormant → called senescence
● control systems in the cell can induce cell suicide → ex.
peeling skin when sunburn
● accumulated mutations cause cell to escape the normal
controls of cell cycle → becomes cancerous
Mutations, Genotypes, Phenotypes:
● More than 1900 mutations of several types have been identified in the cystic fibrosis
gene
○ genetic variability contributes to the range of phenotypes in cystic fibrosis
Epigenetic Changes Involve Reversible Alterations to the Genome:
●
●
●
Epigenetics
○ study of chemical modifications of chromosomal DNA and/or associated
histone proteins that change the pattern of gene expression without affecting
the nucleotide sequence of the DNA
Epigenetic trait
○ phenotype that is produced by epigenetic changes to DNA
Epigenome
○ epigenetic state of the cell
■ can change many times during a lifespan depending on environmental
factors
○ DNA is modified by epigenetic changes
■ how DNA is organized
■ how genes are activated and silenced
● promotor region
○ regulatory region located at beginning of a gene
● methylation
○ addition of a methyl group to a DNA base or a protein
■ methylation occurs almost exclusively on
cytosine bases adjacent to a guanine base
○ What is imprinting?
■ genomic imprinting
● selective expression of either the maternal or paternal copy of
a gene
○ only genes in certain regions of seven human
chromosomes are known to be imprinted
○ many imprinted genes control patterns and timing of
prenatal growth
○ abnormalities of imprinting can cause growth-related
disorders
■ ex. Prader-Willi syndrome
Epigenetics and Behavior:
● Rats with nurturing mothers had 90% less methylation in the GR gene promoter,
higher rates of GR genes transcription, more cell-surface receptors, and more
moderate stress response than non-nurtured rats
Chapter 12:
Cancer is a Genetic Disorder:
● Cancers have two properties:
○ uncontrolled cell growth
○ ability to spread or metastasize to other sites in the body
■ you can have a benign tumor or a malignant tumor
■ the risk of cancer is highly age-related
● Theodor Boveri
○ first to propose link between genetics and cancer
○ four lines of evidence support this
■
■
■
●
there is a predisposition to more than 50 types of cancer
most chemicals that cause cancer also cause mutations
some viruses carry genes that promote and maintain the growth of
cancer in infected cells
■ specific chromosomal changes are found in certain forms of cancer
● most mutations occur in somatic cells, only 1% occur in germ
cells and are passed on
Mutations that can cause cancer include
○ variations in gene copy number
○ single nucleotide substitutions
○ insertions or deletions
○ chromosome rearrangements
Cancer begins in a Single Cell:
● Cancers have several characteristics
○ cancer begins in a single cell
○ a cell becomes cancerous after it accumulates a number of specific mutations
over a period of time
○ once formed, cancer cells divide continuously
○ cancer cells are invasive and can infiltrate surrounding tissues
■ Cancer Develops in Several Steps
● in certain families some members inherit a mutant allele that
causes predisposition to cancer
● all somatic cells in these individuals are heterozygous
● mutation in the other normal allele must occur for cancer to
break out
○ this event is known as loss of heterozygosity
Cancer-Causing Mutations Disrupt Cell-Cycle Regulation:
● Cell growth and division are regulated by many genes, whose protein products
respond to external signals and control progress through the cell cycle
○ if cells carry mutant alleles for these regulatory genes, cells can bypass the
checkpoints of the cell cycle and divide continuously with the mutant genes
■ The cell cycle is regulated and passes through three main checkpoints
● G1 just before cells enter S
● At the transition between G2 and M → ensures DNA has been
replicated and repaired
● A point in late metaphase of mitosis called the M checkpoint →
attachment of spindle fibers to chromosomes is monitored
● Signal transduction
○ a cellular molecular pathway by which an external signal is converted into a
functional response
■ some cancers have abnormalities in signal transduction, which causes
them to divide uncontrollably
Two Classes of Cell-Cycle Regulatory Genes are Involved in Cancer:
● Two classes of genes regulate cell cycle checkpoints
○ genes that turn off/decrease the rate of cell division
○
○
genes encoding proteins that suppress cell division
■ tumor-suppressor genes
genes that turn on/increase the rate of cell division
■ oncogenes
● genes that induce or continue uncontrolled cell proliferation
○ mutant proto-oncogenes in cancerous cells are often
switched on permanently or overproduce their products
■ the products of these genes normally act in the
G1/S or G2/M phase
■ proto-oncogenes
● code proteins that start or maintain cell growth and division
The RB1 tumor suppressor gene controls the G1/S checkpoint
● the RB1 gene encodes for a protein pRB which is always present in the nuclei of all
cell types
○ pRB controls progression through the cell cycle
■ if pRB is switched off in G1 it continues to move through the cell cycle
and divides
■ if both copies of the RB1 gene are mutated → cancer
The Ras Genes are Proto Oncogenes that regulate growth and division
● Differences between protooncogenes and oncogenes
○ single base changes that produce an altered gene product
○ mutations that cause underproduction or overproduction of the normal gene
product
○ mutations that increase the number of copies of the normal gene
■ the ras protooncogene family encodes signal transduction proteins
that transmit signals from the outside cell and stimulates cells to divide
● ras protein cycles between an active and inactive state
○ analysis of mutant ras genes show → single nucleotide
changes at one or two sites in the gene are the only
differences between proto oncogenes and oncogenes
Mutant Cancer Alleles Impair DNA Repair Systems and Genome Stability:
● All forms of cancers share several properties
○ higher-than-normal rates of mutation
○ abnormalities of chromosome structure and number
○ one or more forms of genomic instability
● Breast Cancer
○ Mutations in at least two different genes can predispose women to breast
cancer
■ BRCA1 & BRCA2
● these genes are involved in DNA repair
○ in cancerous cells, expression of BRCA1 & BRCA2 is
highest at the G1/S transition
● Colon Cancer is a Model for the Development of Cancer
○ Inherited predispositions lead to colon cancer along one of two pathways
■
Genetic disorders with DNA repair defects have chromosome
instability and a susceptibility to cancer
● Familial adenomatous polyposis (FAP)
○ results in the development of polyps that can develop
into malignant growths and cause cancer over time
○ causes chromosomal instability through
○ the accumulation of 5-7 mutations in a single cell
○ a specific sequence of mutational events meaning that
both the number and the order of mutations are
important in tumor formation
● Hereditary nonpolyposis colon cancer
○ associated with genomic instability and alterations in
the number of microsatellite repeats and changes in
repeat sequence
Genomics, Epigenetics, and Cancers:
● Cancer is genomic disease generated by the accumulation of number of specific
mutations in tumor-suppressor genes and protooncogenes
○ scientists can now sequence and identify all the mutations present in a cancer
cell
○ genomic studies have greatly expanded the number of genes associated with
many forms of cancer
■ ex. in breast cancer “rare high-risk alleles”, “rare moderate-risk
alleles”, and common but low-risk alleles have been identified
● Epigenetics and Cancer
○ Abnormal patterns of DNA methylation are associated with many types of
cancer
○ Imprinting is also involved in cancer
● New Therapies for Treating Cancer
○ Targeted therapy uses drugs that stop the growth of cancer cells by
selectively blocking the action of oncogene proteins on the growth and
division of malignant cells
■ targeted therapies use two types of drugs
● small molecules directed at specific cancers
● monoclonal antibodies that bind to cancer cells, stop growth,
and mark the cells for destruction by the body’s immune
system
○ these drugs target epigenetic modifications and
reactive genes silenced by methylation or histone
modification
Cancer and the Environment:
● Lifestyle factors and radiation can lead to/ increase the risk of cancer
● Some viral infections can lead to cancer
○ ex. HPV
● Smoking and UV light from the sun can also lead to cancer
Chapter 13:
Chapter 14:
●
●
●
Biotechnology
○ use of recombinant DNA technology to produce commercial goods and
services
Enzyme replacement therapy
○ treatment of genetic disorder by providing a missing enzyme encoded by the
mutant allele responsible for the disorder
How is biotechnology being used?
○ Make pharmaceutical products in genetically altered plants/animals
safely
■ therapeutic proteins for hormone replacement therapy, blood-clotting
factors
● proteins were isolated from slaughterhouse animals, human
cadavers, and human blood
○ increased risk for infection (HIV), immune
response/rejection, and death
■ recombinant DNA technology is used to introduce human genes into
other cells/vectors
● bacteria, transgenic animals and plants
○ many human proteins are grown in bacterial
vectors/hosts → insulin
○ Treat diseases with stem cells
■ Embryonic stem cells
● unspecialized cells in inner mass of early embryo (blastocyst
stage) that will form into specialized cells throughout
development
○ these cells are pluripotent because they can develop
into any cell type
■ Adult stem cells
● cells in bone marrow, umbilical cord blood, thymus
● are multipotent meaning they only have a restricted ability to
form different cell types
■ Induced Pluripotent stem cells (iPS)
● adult cells that can be reprogrammed by gene transfer to form
cells with most of the developmental potential of embryonic
stem cells
○ pluripotent
○ potential to treat wide range of diseases
○ help us understand how developmental errors lead to
birth defects and abnormal phenotypes
○ process:
■ fertilized egg → morula → blastocyst → inner
cell mass → stem cells in petri dish / incubator
○ Produce new varieties of crop plants
■
■
■
○
○
genes can be transferred into crop plants using biotechnology
the transferred gene can originate from another plant, animal, fungus
Genetically modified organisms
● term used to refer to transgenic plants or animals created by
recombinant DNA technology
○ most foods in many countries contain some transgenic
plant material
■ corn, soybeans, canola oil
■ Benefits of GMOs
● enhanced nutritional value in food
● golden rice has more vitamin A → given to people deficient
● resistant to pests → reduced use of pesticides
● tolerant of herbicides → plants no longer killed by herbicides
● more efficient than artificial selection
■ How are transgenic plants made?
● Foreign gene transferred into bacterial plasmid and then
incorporated into plant’s chromosomes → plant cell grows and
divides → some of the daughter cells may go on to mature into
genetically engineered whole plants
Generate animal models of human disease
■ Transgenic
● refers to transfer of genes between species using recombinant
DNA technology
○ transgenic mice share 90% of genes known to be
involved in human diseases
○ mouse models of inherited human diseases are created
by transferring mutant human disease alleles into mice
■ There are several goals for making mouse models of human
diseases
● produce animals with symptoms that mirror those in humans
● use the mice models to study early stages of development and
progress of diseases
● test drugs to treat symptoms/cure diseases
■ How are mice models made?
● copy of mutant allele cloned into vectors and microinjected into
nuclei of fertilized mouse eggs → eggs implanted into foster
mother → birth of transgenic mice some with human
phenotype of disease and some without
Prepare DNA profiles for forensics
■ Minisatellites
● nucleotide sequences 14 - 100 base pairs long, organized into
clusters of varying lengths on many different chromosomes
○ led to development of DNA fingerprints
■ Short tandem repeats
● short nucleotide sequences 2 - 9 base pairs long found
throughout the genome organized into clusters of varying
lengths
○ used in construction of DNA profiles nowadays
■
○
DNA profiles reveal variation in the DNA sequences between
individuals
● in criminal investigations the CODIS panel is used which is a
set of 13 STRs
■ Process of making DNA profiles
● sample is taken and DNA material is amplified using PCR
● sample is analyzed to establish which alleles of the CODIS
panel are there
● results are analyzed to see frequency of STR allele
combinations are present in a population
● population frequencies for each allele are multiplied to
estimate probability that anyone who carries the combination
of STR alleles found
● frequencies are multiplied as STRs on different chromosomes
are inherited independently
○ Applications of DNA profiling
■ forensics
■ paternity tests
■ food contamination (by human feces)
Social and ethical questions
■ Biotechnology has developed faster than public policy
● Ethical questions that remain
○ Should GMOs be labeled
○ Who has access to our genetic material and why
○ Should we test for diseases where there is no cure
○ Should animal models be used
○ Is it unethical to use embryonic stem cells
Chapter 15:
● Genome sequencing is an extension of genetic mapping:
○ Catalogs of mutations were established and research using these mutations
provided insights into genome organization
○ Mutational analysis
■ method of choice for establishing how many genes are contained in
an organism’s genome
○ Genetic mapping
■ establishing number, location, and functions of all genes in a genome
● crossing over frequencies used to construct genetic maps
showing
○ order of genes on chromosome
○ distance between genes on chromosome
● Methods used
○ pedigree analysis
○ linkage analysis
■ linkage is condition where two or more genes
don't show independent assortment, but are
inherited together on same chromosome
■
■
○
●
●
when degree of crossing over (recombination)
between linked genes measured, distance
between them can be determined
distance between alleles can be calculated by
measuring how often they are separated by
crossing over
● Centimorgan
○ unit of distance between genes
on a chromosome
Positional cloning
■ use of DNA sequences rather than genes as genetic markers in
linkage studies
■ method of mapping and cloning genes with no prior information about
the gene product or function
● markers that detected differences in restriction enzyme cutting
sites or differences in the number of repeated DNA sequences
in a cluster, assigned to chromosomes became valuable tool
for linkage studies → positional cloning
Genome projects are an outgrowth of recombinant DNA Technology
○ 1990 the Human Genome project starts
■ set out to sequence all DNA in a human genome and other organisms’
genomes used in experimental genetics
■ main goals
● identify and map all human genes
● determine functions of all human genes
○ Genome project timeline → in book page 330
Genome projects have created new scientific fields
○ Genomics
■ study of the organization, function, and evolution of genomes
● Goals of Genomics:
○ create genetic and physical maps of genomes
○ compile lists of expressed and unexpressed sequences
○ explain gene function and regulation
○ compare genes and proteins between species
○ identify proteins encoded by a genome and their
functions
○ Size of eukaryotic genomes required the development of new
technologies
■ automated DNA sequencing
■ new software to collect, analyze, access and store genome sequence
data
● Bioinformatics
■ Comparative genomics
● compares the genomes of different species to look for clues to
our evolutionary history of genes
■ Structural genomics
● branch of genomics that generates 3-D structures of proteins
from their amino acid sequence
■
●
●
●
●
●
●
●
●
Pharmacogenomics
● use of biotechnology to identify genetic variation that influence
an individual's response to therapeutic drugs
Genomics: sequencing, identifying, and mapping genes
We have an estimated 20000 genes in our human genome
○ Genome sequencing involves
■ cutting genomic DNA into manageable fragments using restriction
enzymes
■ sequencing of fragments
■ assembling DNA fragment sequence data
Two main sequencing strategies are used to correctly assemble the sequence
of cut DNA fragments
○ map-based sequencing
■ clone-by clone method
■ begins with physical and genetic maps
■ clones are first assembled in order, followed by sequencing
● physical map
○ diagram of chromosome showing order of genes and
the distance between them measured in base pairs
○ whole genome sequencing
■ shotgun method → because efficient
■ DNA clones are first sequenced, followed by assembly of the
sequences using software analysis
Annotation
○ analysis of genome sequence to find all the genes that encode proteins and
RNA
Open reading frame
○ DNA sequence in a gene that encode the amino acids of a protein
■ analysis of amino acid sequence can determine gene function
● genes leave certain identifiable footprints open reading frames
are one
Promoter sequences
○ indicates the beginning of a gene
Splice sites
○ indicates locations of exons and introns
What have we learned so far about the human genome
○ About 2% of our genome contains protein-coding sequences and about 1% is
composed of exons specifying amino acid sequences in a protein
○ Gene rich regions on chromosomes are separated by gene poor regions
○ We have about 20000 genes
○ We have many more proteins than we have genes due to differential mRNA
processing
○ We share many of our genes with other species
○ Different mutations in a single gene can give rise to different genetic disorders
○ Nucleotide variation in genomes is common
■ Single nucleotide polymorphism (SNP)
● single base difference in DNA sequence
■ Haplotype
●
●
SNPs located closely together on a chromosome that tend to
be inherited together
■ Copy number variant
● these variations in the nucleotide sequence may include
○ duplications, or deletions
○ CNVs can affect gene expression in several ways:
■ They may increase or decrease the dosage of a
gene
■ They may insert into coding sequences creating
mutations
■ Their presence may interfere with long-range
gene regulation
■ A DNA segment at least 1000 base-pairs long
with a variable copy number in the genome
■ CNVs may be associated with a significant
number of complex genetic disorders
Using genomics to study a human genetic disorder
○ Important questions to ask
■ Where is the gene located?
■
What is the normal function of the protein encoded by this gene?
■
How does the mutant gene or protein produce the disease
phenotype?
●
●
The human microbiome is our other genome
○ The human microbiome is the collection of microbes that live on and in our
body
■ Microbial genes outnumber ours by 100 to 1
■ Microbes contribute to our survival
○ Human Microbiome project
■ goal to identify and characterize microbial communities that inhabit the
body
● Microbial DNA has been sequenced and cataloged
Proteomics is an extension of genomics
○ Proteome
■ set of proteins present in a cell at a specific time under a specific set
of environmental conditions
○ Proteomics
■ study of the proteome, the set of expressed proteins present in a cell
■ Proteomics is a rapidly developing field with several crucial
roles:
● Understanding gene function and its role in development
and aging
● Identifying proteins that are biomarkers for disease, to be
used for diagnostic testing
● Identifying proteins that can be targets for drug
development
●
Ethical concern about human genomics
○ Ethical legal and social implications (ELSI) is focused on several issues:
■ Privacy and confidentiality of genetic information
■ Fairness in the use of genetic information by insurers, employers, and
others
■ Discrimination caused by someone’s genetic status
■ Use of genetic information in reproductive decisions
● these worries led to the passage of the genetic information
nondiscrimination act
Chapter 16:
● Infertility is a common problem:
○ Successful reproduction requires
■ healthy gametes
■ a place for fertilization to occur
■ a place for the embryo to develop
● Two types of infertility
○ primary infertility
■ trouble conceiving first child
○ secondary infertility
■ trouble conceiving another child after first child
● Causes of infertility
● 40% male factors
○ low sperm count
■ oligospermia due to environmental and lifestyle
factors
● most common cause of low sperm count
is varicocele (enlarged veins that raise
temp in testes)
○ can be surgically corrected
● low sperm motility
○ sperm moves too slowly through cervical mucus
■ due to malformed sperm or unorganized
swimming
● no sperm in semen
○ azoospermia through blockage of the epididymis or vas
deferens caused by UTIs or STDs
○ 40% female factors
■ hormone levels
● low estrogen
■ ovarian problems
● damage to ovaries through surgery, inflammation, autoimmune
disease
■ oviduct and uterine problems
● oviduct blockage through infections and scarring,
● uterine problems due to endometriosis
○
●
20% unexplained
■ age, tobacco use, drug use, environment
Assisted reproductive technologies expand child bearing options:
○ ART focuses on three areas to assist individuals in getting pregnant
■ retrieval and donation of gametes
■ fertilization
■ implantation of an embryo
● Intrauterine insemination with donor sperm (IUI)
○ method to overcome male infertility
○ female partner has donor sperm placed in uterus while
she is ovulating
● Egg retrieval combined with IVF
○ infertile women who ovulate but have blocked oviducts
can have their eggs retrieved and frozen until they
would like to have them fertilized
■ discovery that the age of the egg and not the
age of the reproductive system is leading factor
behind age-related infertility
● Egg donor combined with IVF
○ women can also use donor eggs and fertilize these with
the sperm of their partner
● IVF combined and related procedures
○ In vitro fertilization is a procedure in which gametes are
collected and fertilized in a dish in a laboratory →
placed in an incubator for cell growth → the zygote
then is implanted in the uterus for development
■ gametes used for IVF can come from a couple,
from donors entirely, or from a combination of
the two depending on the type of infertility
experienced
● Intracytoplasmic sperm injection
○ variation of IVF
○ treatment to overcome defects in sperm count and
mobility
○ egg injected with a carefully selected single sperm
○ GIFT & ZIFT are variations of IVF:
■ Gamete intrafallopian transfer
● assisted reproductive technology in which gametes are
collected and placed into a women’s oviduct for fertilization
○ method where infertility is not the result of oviduct
blockage
■ Zygote intrafallopian transfer
● assisted reproductive technology in which gametes are
collected, fertilized in dish, and the resulting zygote is
transferred to a women’s oviduct
○ method used in cases where women have ovulation
issues, or man has low sperm count and oviducts are
not blocked
○
●
●
●
Surrogacy
■ when a woman is hired to carry a child either partly her own or zygote
made through IVF of couple who hired her
Ethical issues in reproductive technology
○ There are several moral, ethical and legal issues surrounding ART:
■ higher incidence of multiple births
■ low birth weight
■ higher risk of ectopic pregnancies
■ high medical costs
■ higher risk of birth defects
Genetic testing and screening
○ Genetic testing
■ use of methods to determine if someone has a genetic disorder, will
develop one, or is a carrier
■ voluntary
● carrier testing
● pre-symptomatic testing
● prenatal testing
○ traditional methods of prenatal testing are risky to
mother and fetus
○ not all genetic testing is accurate
○ Genetic screening
■ systematic search for members of a population with certain genotypes
■ mandatory
● e.g.,newborn screening
○ Preimplantation genetic diagnosis (PGD)
■ removal and genetic analysis of a single cell from a 3-5 day old
embryo
■ used to select embryos free of genetic disorders for implantation and
development
● process:
○ eggs are fertilized in laboratory → develop in a culture
dish for several days → one of the six - eight embryonic
cells (blastomeres) is removed → DNA is extracted and
amplified using PCR → tested to determine whether
the embryo is hemi or homozygous for a genetic
disorder
■ PDG and ethical issues:
● PDG used to select embryo to be a stem cell donor for a child
that has a genetic disorder, or needs organ transplantation
● other controversial reasons PDG is employed
○ non-medical sex selection
○ selection for disabilities
○ to avoid adult onset genetic diseases
Therapy for genetic disorders:
○ Enzyme replacement therapy
■ treatment by IV infusion, that provides an enzyme to someone in
whom the enzyme is missing or nonfunctional
●
● not a cure, but treats symptoms
○ Gene therapy
■ transfer of cloned genes into somatic cells as a means of treating a
genetic disorder
■ expression of transferred, correct copy of mutant allele will produce a
functional protein that restores cellular function and results in normal
phenotype
■ provides a cure
● gene therapy requires:
○ normal gene → clone normal gene → transfer to viral
vector (delivery system) → infect patient’s white blood
cells with viral vector → viral DNA with normal form of
mutant allele inserts into chromosome(s) → cure of
genetic disorder
○ Exon skipping
■ directed removal of exons during mRNA processing to restore the
reading frame of a mature mRNA to make a shortened, but functional
protein
■ process:
● exon deletion through mutation cause frameshift and
translation terminates where it shouldn’t → exon specific AON
inserted through injection – AON binds to exon and blocks
splicing signals → mutant exons are skipped over and
removed along with introns during processing
○ Antisense oligonucleotides (AONs)
■ short, single stranded DNA or RNA molecule synthesized to be
complementary to a sequence of interest
○ Other variations of gene therapy:
■ Somatic gene therapy
● gene transfer to somatic cells to cure genetic disorder
■ Germ-line gene therapy
● gene transfer to gametes to prevent genetic disease
● new gene then passed on to new generation
■ Enhancement gene therapy
● gene transfer to enhance traits
● e.g., gene doping used in extreme sports because hard to
trace
Genetic counseling:
○ Counseling that helps people understand the occurrence and risks of having
a genetic disorder in their family by reviewing a few factors:
■ medical facts, diagnosis, treatment
■ how heredity contributes to risk of having a disorder and affected
children
■ alternatives for dealing with risks of recurrences
■ how to adjust to an individual with a genetic disorder or the risk of
developing one
● Who seeks counseling?
○ pregnant women over age 35
○
○
couples with a child affected by a genetic disorder or
other disability
couples belonging to ethnic groups with higher risks for
genetic disorders
Chapter 17:
● Our body has three levels of defense:
○ The skin and the organisms on it
○ skin is physical barrier to pathogens
■ mucus and lysozymes kill invading bacteria by breaking down their
cell walls
○ The innate immune system
■ uses nonspecific responses such as inflammation
■ series of chemical reactions and cellular responses
● process:
○ microorganisms penetrate the skin at a wound →
macrophages (blood cells) detect and bind to surface of
invading bacteria → macrophage engulfs and destroys
the bacteria at the wound and secrete chemicals called
cytokines and histamine → these chemicals cause near
capillaries to dilate, increasing blood flow to the area
→ heat causes unfavorable environment for bacterial
growth and raises metabolic rate in nearby cells → if
infection persists blood clots, due to neutrophils,
preventing further penetration of bacteria → white
blood cells (phagocytes) clean up dead bacteria and
dispose of dead cells
○ The adaptive immune system
■ uses specific responses to infection
■ most effective system
■ has a memory component
■ recognizes pathogens and responds to neutralize or kill invaders
● includes two components
○ antibody-mediated immunity
■ immune reaction that protects against invading
viruses and bacteria using antibodies produced
by plasma cells
■ regulated by B cells and helper T-cells
○ cell-mediated immunity
■ immune reaction mediated by T cells directed
against body cells that have been infected by
viruses or bacteria
■ regulated by cytotoxic killer T cells
● directed against cells infected by
pathogens, cancerous cells, and
transplanted cells
○ Cells involved in adaptive immunity:
○
●
lymphocytes
■ white blood cells originating from bone marrow → mediates immune
response
○ B cell
■ type of lymphocyte that matures in bone marrow →: mediates
antibody-directed immunity
● produces antibodies on cell surface → antibodies bind to
antigens on pathogen cell surface each B cell produces
different type of antibody
● Plasma cell
○ daughter cells of B cells
○ T cell
■ type of lymphocyte that undergoes maturation in the thymus →
mediates cellular immunity
● migrate to thymus as immature cells → mature cells circulate
and are found in spleen,and lymph nodes → produce T-cell
receptors → T-cell receptors bind to pathogen proteins on
surface of infected cells
○ Helper T cell
■ lymphocyte that stimulates the production of antibodies by B cells
when an antigen is present and stimulates division of B cells and
cytotoxic T cells
○ Antibody
■ class of proteins produced by B cells that bind to foreign molecules
and inactivate them
○ Antigens
■ molecules carried or produced by viruses or microorganisms, or cells
that initiate antibody production
○ T-cell receptors
■ unique proteins on surface of T cells that bind to specific proteins on
the surface of cells infected with viruses or bacteria
○ pathogens
■ disease-causing agents
● fungi, bacteria, viruses, parasites
○ Genetic disorders can cause inflammatory diseases
■ IBS, crohn's disease, arthritis
The complement system kills microorganisms:
○ Chemical defense system that kills microorganisms directly, and supplements
the inflammatory response → it compliments both innate and adaptive
immune system
■ system consists of 20-30 proteins synthesized in liver and excreted in
blood
■ Stages of complement system reactions:
● complement proteins activated at site of infection → cascade
of activated complement proteins → formation of membrane
attack complexes → lysis (auflösung) of the pathogen(s)
○ Major histocompatibility complex
■
●
●
●
set of 140 genes on chromosome 6 that encodes recognition
molecules that prevent the immune system from attacking body's own
cells
● Antibody structure → see picture in book page 374
○ Cell-mediated immune response
■ process:
● formation of antigen presenting cell → antigen on APC bind to
T cell receptor on CD 8+ cell → Clonal expansion of CD8 + cell
into cytotoxic and memory T cells → cytotoxic T cells attach to
infected cells and secrete perforins → debris from dead cells
removed by phagocytes
Blood types are determined by cell surface antigens:
○ Blood typing is based on presence or absence of certain proteins on the
surface of red blood cells
■ two blood groups of major significance:
● Rh group
● ABO group
○ individuals produce antibodies against antigens that are
not on the surface of their own red blood cells
■ e.g., if type A you will produce antibodies
against type B
■ basis for blood type matching for transfusions
■ Process of blood transfusion reaction:
● false blood type is transfused → antigens do not recognize
blood as own, and antibodies are created to attack blood cells
of other blood type → causes blood clotting or red blood cells
to burst → accumulation of hemoglobin in kidneys which
blocks filtration, oxygen and nutrient flow to cells and tissues is
severely reduced
Organ transplants must be immunologically matched:
○ Successful organ transplants depend on matches between cell-surface
antigens of the donor and the recipient
■ the antigen proteins / identification tags our found on all cells of the
body to distinguish self from nonself
■ those antigens are encoded by major histocompatibility complex
● a set of 9 genes on this complex are known as human
leukocyte genes
○ Haplotype
■ the set of human leukocyte genes located close together and carried
on each copy of chromosome 6
● organ donors and recipients are matched by testing for human
leukocyte compatibility
Biotechnology makes Xenotransplants possible:
○ Two biological problems are related to xenotransplants (animal organs
transplanted into humans):
■ complement-mediated rejection
■ T cell mediated rejection
●
●
Transgenic pigs carrying human HLA genes overcome either
rejection
Disorders of the immune system:
○ Mutation in the genes associated with the immune system can cause immune
system disorders including:
■ overreaction of the immune system
● allergies, anaphylaxis shock
● process:
○ allergen in allergic person produces allergen specific
antibody at first time exposure → these antibodies
attach themselves to mast cells → second time
exposure then causes the allergen specific antibodies
to release histamines and cytokines → cause allergy
symptoms
■ abnormal immune reactions
● autoimmune diseases like MS
■ immune system deficiencies
● Severe combined immunodeficiency disease
■ Viral diseases
● HIV
○ virus that leads to AIDS
■ HIV infects and destroys T helper cells
■ process of HIV replication:
● viral RNA enters T helper cell → viral
RNA forms by reverse transcription of
viral RNA → viral DNA becomes
integrated into host cell’s DNA → DNA
including the coral genes is transcribed
→ new viral RNA that produce mutated
proteins and assemble as new virus
particles
● AIDS → acquired immune deficiency syndrome
○ collection of disorders after exposure to HIV virus
Chapter 18:
Models, methods, and phenotypes in studying behavior:
Models:
Single gene model
one gene controls a defined behavior
polygenic trait
two or more genes contribute equally to phenotype with other genes genes making lesser
contributions
epistasis
complex trait
two or more genes interact with each other and environmental factors to produce phenotype
Behavior genetics is studies using:
genome-wide association studies
looking for associations between behavioral trait and single nucleotide polymorphisms
exome sequencing
epigenetic analysis
Defining behavior and its phenotypes:
Behavior → reaction to internal and external stimuli that alters an organism’s response to
environment
whether behavioral phenotype is defined narrowly or broadly can affect the outcome of the
genetic analysis and model of inheritance for a given trait
The nervous system is the focus of behavior genetics:
CNS
Spinal cord
brain
PNS
nerves that radiate from CNS and sense organs
diseases of the nervous system alter structure and function of the brain and nervous system
Synapses interconnect cell in the nervous system
synapse
junction between two nerve cells where nerve impulses are transmitted and received
7,5 % of genome encodes protein associated with structure and function of synapse
synaptic defects through genetic mutations can cause many genetic disorders with
behavioral components
e.g., alzheimer's, bipolar disorder, autism
synaptic cleft
small gap between neurons across which nerve impulses are transferred
nerve cells have two ends:
axon terminals (where synapses are found)
transmits nerve impulses to dendrites
dendrites
receive nerve impulses and move them forward towards axon
neurotransmitters
chemical(s) that transmit a nerve impulse from one neuron to another
package in vesicles at axon terminals
changes in timing or duration of neurotransmitter action can affect someone’s behavior and
mood
common neurotransmitters:
acetylcholine → muscle stimulation, learning, sleep
dopamine → memory, mood, positive reinforcement
GABA → motor control, anxiety, inhibitory
Serotonin → sleep, mood, pain, appetite
Single gene mutations cause behavioral disorders:
X-linked behavioral disorder discovered
associated with antisocial behavior
gene encodes enzyme MAOA
failure to rapidly break down these chemicals disrupts normal synaptic function
Huntington Disease is a model for neurodegenerative disorders:
Autosomal dominant disorder associated with progressive neural degeneration and
dementia
adult onset disorder
caused by the expansion of a CAG trinucleotide
mutant protein made by mutant gene found in all parts of the brain
most active in two parts:
striatum
cerebral cortex
Animal models: the search for behavior genes
Chapter 19: