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At the cellular and genetic levels, cancer is
usually a multistep process
Once a cancerous cellular growth has become malignant
the cells are invasive (that is, they can invade healthy tissues)
Cancerous cells are also
metastatic (that is, they can migrate to other parts of the body)
Oncogene
a mutant gene that is overexpressed or hyperactive and contributes to cancerous growth
Tumor-suppressor gene
a gene that prevents cancer. Loss-of-function mutations in these genes allow cancerous growth to occur
Proto-oncogenes that are involved in the cell cycle can be
mutated to become oncogenes, which causes unregulated cellular division
Tumor-suppressor genes that normally regulate the cell cycle can be
inactivated, which causes unregulated cellular division
Because there are two copies of most genes, only one copy of proto-oncogenes
need to be affected to cause cancer, while both copies of tumor-suppressor genes usually need to be inactivated to cause cancer
Oncogenes promote
abnormal cell growth
Proto-oncogenes are
normal cellular genes that can be mutated into an oncogene
egf
Epidermal growth factor
ngf
Nerve growth factor
sis
Platelet-derived growth factor
erbB
Growth factor receptor for EGF (epidermal growth factor)
fms
Growth factor receptor for NGF (nerve growth factor)
ras
GTP/GDP-binding protein
raf
Serine/threonine kinase
src/abl
Tyrosine kinase
myc/jun/fos
Transcription factor
Tumor-suppressor genes play
a role in preventing the proliferation of cancer cells
rb
The protein is a negative regulator of E2F (see Figure 25.14). The inhibition of E2F prevents the transcription of certain genes required for DNA replication and cell division
p16
a protein kinase that negatively regulates cyclin-dependent kinases. This protein controls the transition from the G1 phase of the cell cycle to the S phase
NF1
The protein stimulates Ras to hydrolyze its GTP to GDP. Loss of function causes the Ras protein to be overactive, which promotes cell division
APC
a negative regulator of a cell-signaling pathway that leads to the activation of genes that promote cell division
p53
a transcription factor that acts as a checkpoint protein and positively regulates a few specific target genes and negatively regulates others in a general manner. It acts as a sensor of DNA damage. It can prevent progression through the cell cycle and also
can promote apoptosis
BRCA-1, BRCA-2
proteins are both involved in the cellular defense against DNA damage. These proteins facilitate DNA repair and can promote apoptosis if repair is not achieved.
Most cancers are caused by
mutations in multiple genes, but the order of the
mutations is not necessarily important
Tumor cells often have
missing, extra and rearranged chromosomes
Inherited mutations in either oncogenes or tumor suppressor genes can
lead to a predisposition for developing cancer
Abnormalities in chromatin modification are
common in cancer cells
morula
16-cell stage
blastula
32-cell stage
gastrula
64-cell stage
The uniformity of the dividing cells in a developing animal clearly start
to differentiate at the gastrula stage
Morphogens
molecules that convey positional information and promote developmental changes
Morphogens can
act at the earliest stage of development in the unfertilized oocyte
homeotic gene
Genes that specify the final identity of a body region
anteroposterior axis
head-tail
dorsoventral axis
up-down or front-back
An adult fly emerges from its pupal case with four definable axes:
anteroposterior axis, dorsoventral axis, left-right axis, and proximodistal axis
proximodistal axis
how the limbs are attached to the body
There are three classes of segmentation genes:
Gap genes, pair-rule genes, and segment-polarity genes
Sequential expression of gap, pair-rule and segment-polarity genes divides the embryo into segments
Maternal effect genes to gap genes to pair-rule genes to segment-polarity genes
homeotic mutant
refers to mutant alleles in which one body part is replaced by another
polycomb genes
represses the expression of homeotic genes in regions of the embryo where they should not act
trithorax genes
promote the expression of homeotic genes in regions of the embryo where they should act
Male (XO) (nematode):
Produce sperm
An adult male is composed of 1,031 somatic cells
Hermaphrodites (XX) (nematode):
Produce sperm and eggs
An adult hermaphrodite is composed of 959 somatic cells
cloned genes from simpler organisms such as Drosophila are used
as probes to identify homologous vertebrate genes
By comparison, plants have two axes:
Root-shoot axis and radial axis
Root-shoot axis
Most plant growth occurs via cell division near the tips of the shoots and the bottom of the roots
Radial axis
A plant shoot gives off the buds that give rise to branches, leaves and flowers
In insects XX are female, XY and X0 are male
The X chromosome dictates femaleness and is governed by the Sxl gene
An insect lacking two X chromosomes is male
In animals, XX and X0 are female, XY and XXY are male
The Y chromosome dictates maleness and is governed by the SRY gene
An animal with a Y chromosome is male and an animal lacking a Y chromosome is female
In Drosophila the Sxl gene dictates
femaleness and is active in females and inactive in males
In male animals
the SRY gene is active
polymorphism
refers to the observation that many traits display variation within a population
At the DNA level:
polymorphism occurs when two or more alleles influence a phenotype
Polymorphic is also used to
describe a gene that commonly exists as 2 or more alleles in a population
The allele frequency formula
look at it
The genotype frequency formula
look at it
For a given trait, the allele and genotype frequencies are
always less than or equal to 1
For polymorphic genes
The frequencies of all of the alleles should add up to 1
Note that the Punnett square analysis gives the
same result mathematically as the Hardy Weinberg equation p2 + 2pq + q2 = 1
Hardy Weinberg equation
look at it
Mechanisms that alter existing genetic variation:
Natural Selection, random genetic drift, migration, and nonrandom mating
Simply stated, natural selection is
the survival of the fittest
Simply stated, beneficial alleles are
favored in a population
Darwinian fitness
a quantitative assessment of the relative likelihood that a genotype will survive and contribute to the gene pool of the next generation
Darwinian fitness or relative fitness values (w)
a measure of reproductive superiority and it should not be confused with physical fitness
Four patterns of natural selection
Directional selection, balancing, disruptive or diversifying selection, and stabilizing selection
Directional selection
Favors the survival of one extreme phenotype that
is better adapted to an environmental condition
Balancing
Favors the maintenance of two or more alleles
Disruptive or diversifying selection
Favors the survival of two or more different phenotypes
Stabilizing selection
Favors the survival of individuals with intermediate phenotypes
Directional selection favors
individuals at one extreme of a phenotypic distribution
that are more likely to survive and reproduce in a particular environment
Directional selection affects
the Hardy-Weinberg equilibrium and allele
frequencies by favoring the extreme phenotype as determined by w, the relative fitness value
The mean fitness of the population, (wU), formula
look at it
There are two types of balanced polymorphisms
Heterozygote advantage and negative frequency-dependent selection
Heterozygote advantage
the heterozygote has a higher fitness than either homozygote
Negative frequency-dependent selection
the fitness level of a genotype decreases when its frequency becomes higher- rare individuals have a higher fitness level than the more common individuals- rare individuals are more likely to reproduce, which produces a balanced polymorphism
The selection coefficient formula
look at it
Complex traits
traits that are determined by multiple genes and influenced by environmental factors
Quantitative traits
traits that can be described numerically
continuous traits
they do not fall into discrete categories (ex. height and weight)
meristic traits
traits that can be expressed in whole numbers (ex. bristle hairs on flys)
threshold traits
traits that are inherited due to the contributions of many genes (ex. often diseases)
Biometrics
the statistical study of biological traits
Variance (VX)
the deviance from the mean for measurable values in a group
Polygenic inheritance
transmission of traits that are governed by two or more genes
Polygenic traits or phenotypes are
influenced by both the genetic makeup and the environment
Environmental impact increasingly skews the
Mendelian inheritance ratio as more and more genes
are involved
Both genetic variance and environmental variance
contributes to
the overall phenotypic variance that is observed for a trait
Heritability
the amount of phenotypic variation within a group of individuals that is due solely to genetic variation
Broad sense heritability (hB2)
takes into account all of the different types of genetic variation that may affect the phenotype
narrow sense heritability (hN2)
The heritability of a trait due solely to the additive effects of alleles (VA)
Can calculate narrow sense heritability as
look at chapter 28
The closer the relationship between genetically related individuals
the higher the rexp becomes
Selective breeding
the modification of phenotypes in plant and animal species of economic importance
Selective breeding is also called
artificial selection