Cancer: Cellular and Genetic Processes

Cancer: Cellular and Genetic Processes

• Cancer is a multistep process at the cellular and genetic levels.
• Malignant cells are invasive, able to invade healthy tissues.
• Malignant cells are metastatic, able to migrate to other parts of the body.
• Oncogenes are mutant genes that are overexpressed or hyperactive, contributing to cancer growth.
• Tumor suppressor genes prevent cancer; loss-of-function mutations allow cancer growth.
• Proto-oncogenes, involved in the cell cycle, can mutate into oncogenes causing unregulated division.
• Tumor suppressor genes, regulating the cell cycle, can be inactivated causing unregulated division.
• One copy of a proto-oncogene needs mutation to cause cancer, while both copies of a tumor suppressor gene typically need inactivation.
• Oncogenes promote abnormal cell growth.
• Proto-oncogenes are normal genes that can mutate into oncogenes.
• Tumor suppressor genes prevent cancer cell proliferation.
• Major tumor suppressor genes include: rb, p16, NF1, APC, p53, BRCA-a, BRCA-2.
• Most cancers result from mutations in multiple genes. The order of mutations is not critical.
• Tumor cells often have missing, extra, or rearranged chromosomes.
• Inherited mutations in oncogenes or tumor suppressor genes can predispose individuals to cancer.
• Chromatin modification abnormalities are common in cancer cells.

Embryonic Development

Stages of Development

• Morula: 16-cell stage
• Blastula: 32-cell stage
• Gastrula: 64-cell stage

Developmental Factors

• Morphogens are molecules specifying positional information and driving developmental changes.
• Morphogens can influence development in unfertilized oocytes.
• Homeotic genes determine the final identity of body regions.

Developmental Axes and Genes

• Adult flies have four axes: anteroposterior (head-tail), dorsoventral (up-down), left-right, and proximodistal (limb attachment).
• Segmentation genes are categorized as: gap genes, pair-rule genes, and segment-polarity genes.
• Maternal effect genes influence gap, pair-rule, and segment-polarity genes.
• Homeotic mutants replace one body part with another.
• Polycomb genes repress homeotic genes in inappropriate regions.
• Trithorax genes promote homeotic gene expression in appropriate regions.

Sex Determination in Nematodes

• Male nematodes (XO) have 1031 somatic cells in adulthood.
• Hermaphrodites (XX) have 959 somatic cells in adulthood.
• Hermaphrodites have both male and female reproductive organs.

Plant Development

• Plants have a root-shoot axis and a radial axis.
• The root-shoot axis defines tips of shoots and bottoms of roots.
• The radial axis defines buds that form branches, leaves, and flowers.

Sex Determination in Insects

• In insects, XX is female, XY and XO are male.
• X chromosome controls femaleness via the Sxl gene.
• An insect with no two X chromosomes is male.
• In most animals, XX or X0 is female and XY is male.
• Y chromosome determines maleness via the SRY gene.
• In Drosophila, the Sxl gene determines femaleness.
• In animals, the SRY gene determines maleness.

Population Genetics

Polymorphism

• Polymorphism refers to trait variation within a population.
• Polymorphism at the DNA level occurs when two or more alleles influence a phenotype.
• A polymorphic gene commonly exists with two or more alleles.

Allele and Genotype Frequencies

• Allele frequency = (Number of allele copies) / (Total allele copies)
• Genotype frequency = (Number of individuals with a genotype) / (Total individuals)
  • Allele and genotype frequencies are always less than or equal to 1.
  • For polymorphic genes, the allele frequencies sum to 1.0
  • The Hardy-Weinberg equation (p² + 2pq + q² = 1) mathematically describes the results of a Punnett square.

Mechanisms of Genetic Variation

• Natural selection, genetic drift, migration, and nonrandom mating can alter genetic variation.
• Natural selection favors beneficial alleles.
• Darwinian fitness (w) measures reproductive success.

Types of Selection

• Directional selection favors one extreme phenotype.
• Balancing selection maintains multiple alleles.
• Disruptive selection favors multiple phenotypes.
• Stabilizing selection favors intermediate phenotypes.

Genetic Drift

• Genetic drift is random change in allele frequencies due to chance fluctuations.
• Genetic drift affects allele frequencies more quickly in small populations. - Bottleneck and founder effects significantly impact genetic drift.

Inbreeding

• Inbreeding occurs between related individuals.
• Inbreeding coefficient (F) assesses relatedness.
• Low inbreeding coefficients (F < 5%) are preferred for animal health.

Mutations

• Mutations can be beneficial, neutral, or deleterious.
• Neutral and deleterious mutations are more common than beneficial mutations.

DNA Fingerprinting

• DNA fingerprinting uses repetitive sequences to identify individuals. -Matches are used in crime scene investigations.

Quantitative Traits

• Complex traits involve multiple genes and environmental factors.
• Quantitative traits are numerically measurable (e.g., height, weight).
• Quantitative traits can be meristic (whole numbers, e.g., bristles).
• Diseases can be threshold traits with contributions from multiple genes.

Biometrics

• Biometrics statistically analyzes biological traits.
• Mean is the average value.
• Variance (VX) measures deviation from the mean.
• Standard deviation (SD) is a useful measure derived from variance.
• Correlation coefficient (r) evaluates the association between variables.
• Covariance (CoV) underlies the calculation of r.

Polygenic Inheritance

• Polygenic traits involve multiple genes influencing a phenotype.
• Environmental factors influence polygenic traits.
• Genetic and environmental variance both affect the observed phenotypic variance.

Heritability

• Heritability measures how much phenotypic variance is due to genetics.
• Broad-sense heritability (hB²) considers all genetic sources.
• Narrow-sense heritability (hN²) considers only additive genetic variance.

Selective Breeding

• Selective breeding (artificial selection) manipulates traits.
• Inbreeding can reduce genetic variation and increase risk of deleterious alleles (inbreeding depression).
• Heterosis (hybrid vigor) occurs when crosses between different inbred lines create offspring that are more vigorous.

Speciation

Biological Species Concept

• Species are groups whose members can interbreed.
• Members of one species cannot interbreed with members from different species.

Modes of Speciation

• Prezygotic isolating mechanisms prevent zygote formation.
• Postzygotic isolating mechanisms prevent viable offspring development.
• Allopatric speciation (geographic isolation) is common.
• Parapatric speciation involves partial geographic separation.
• Sympatric speciation occurs without geographic separation.

Species Concepts

• Evolutionary species concept emphasizes lineage divergence.
• Ecological species concept relates species to ecological niches.
• General lineage concept is a widely-accepted approach to define species.

Phylogeny

• Phylogeny traces the evolutionary history of species.
• Phylogenetic trees depict species relationships.
• Phenetic method uses overall similarities to build trees (phenograms).
• Cladistic method uses evolutionary pathways to build trees using parsimony

Homologous Genes

• Homologous genes originate from a common ancestral gene.
• Orthologous genes are found in different species.
• Paralogous genes are found within a single species.
• Neutral mutations account for much genetic variation.
• Kimura's neutral theory suggests that most evolution occurs due to random mutation fixation

Explore the intricate cellular and genetic mechanisms that lead to cancer development. This quiz covers key concepts such as oncogenes, tumor suppressor genes, and the differences between malignant and benign cells. Understand how mutations can result in uncontrolled cell growth and proliferation.