Understanding Chromosomes and Genetic Inheritance
Chromatin: DNA-protein complex forming chromosomes. Centromere: Constriction point on a chromosome where spindle fibers attach. Telomere: Repetitive DNA at chromosome ends prevents degradation. Chromatid: One of two copies of a replicated chromosome. Homologous Chromosomes: Chromosome pairs (one from each parent) with the same genes but different alleles. Histones: Proteins that DNA wraps around to form nucleosomes in eukaryotic cells.
Cell Cycle and Division
Interphase:
Period between cell divisions.
G₁ Phase:
Cell growth and preparation for replication.
S Phase:
DNA synthesis; chromosome replication.
G₂ Phase:
Preparation for mitosis; error checking.
G₀ Phase:
Non-dividing phase.
M Phase:
Mitotic phase; includes mitosis and cytokinesis.
Checkpoints:
Control points ensuring proper progression of the cell cycle (G₁/S, G₂/M, spindle checkpoint). p53: Tumor suppressor protein regulating the G₁/S checkpoint.
Mitosis
Stages of Mitosis:
Interphase: Prophase: Chromosomes condense and spindle forms; chromatids become visible, each with two sister chromatids and one centromere; centrioles of microtubules extend towards chromosomes; centrosome holds centrioles at opposite poles. Prometaphase: Nuclear envelope dissolves, spindle microtubules attach to kinetochores of chromatids. Metaphase: Chromosomes align at the metaphase plate, spindles bind to centromeres at kinetochores. Anaphase: Chromatids separate; spindles pull them to opposite poles; chromatids are now individual. Telophase: Chromosomes decondense and the nuclear envelope reforms.
Meiosis
Overview:
Reduces chromosome number by half, resulting in four unique haploid cells. Meiosis I: Homologous chromosomes separate (reductional division). Meiosis II: Sister chromatids separate (equational division).
Key Terms:
Synapsis: Pairing of homologous chromosomes during Prophase I. Tetrad: Structure of four chromatids (two homologous chromosomes) during Prophase I. Crossing Over: Genetic material exchanged between non-sister chromatids in Prophase I. Independent Assortment: Random orientation of homologous pairs during Metaphase I. Chiasma: Physical site of crossing over. Polar Bodies: Small cells produced during oogenesis that usually degenerate. Homologous Chromosomes: Pairs of chromosomes (one from each parent) that carry the same type of gene but different alleles (B vs. b on chromosome 7). Sister Chromatids: Identical copies of a single chromosome, formed during replication in S phase; held together at the centromere. Telomere: Repetitive DNA at the end of chromosomes that prevents degradation. Histones: Proteins that DNA wraps around, forming nucleosomes in eukaryotes; without kinetochores, no spindle microtubules can form, leading to improper segregation of chromosomes.
Proteins and Regulatory Molecules
Cohesin: Holds chromatids together; loss leads to premature separation and aneuploidy. Separase: Cleaves cohesin during anaphase. Shugoshin: Protects centromeric cohesin during meiosis I; loss leads to nondisjunction in gametes. Condensin: Compacts chromosomes; loss leads to entanglement and improper segregation. Cyclins/Cdks: Cell cycle regulators; loss can lead to cancer.
Mendelian Inheritance
First Law – Segregation: Individuals have two alleles for each trait; each gamete receives one (Aa x Aa: 3:1). Second Law – Independent Assortment: Alleles at different loci separate independently during gamete formation (RrYy x RrYy: 9:3:3:1). Incomplete Dominance: Heterozygotes show intermediate phenotypes (e.g., pink flowers). Codominance: Both alleles in a heterozygote are fully expressed (e.g., AB blood type). Epistasis: One gene masks or changes the effect of another gene. Recessive Epistasis: 9:3:4 ratio (e.g., lab coat color). Dominant Epistasis: 12:3:1 ratio (e.g., squash color). Duplicate Recessive Epistasis: 9:7 ratio (e.g., snail albinism). Pleiotropy: One gene influences multiple traits (e.g., Marfan syndrome, sickle cell disease). Penetrance: Probability that a genotype expresses a phenotype. Expressivity: Degree to which a phenotype is expressed. Allelic Heterogeneity: Different mutations in the same gene can result in the same phenotype. Locus Heterogeneity: Mutations in different genes can result in the same phenotype. Anticipation: Genetic disorders become more severe or appear earlier in subsequent generations. Haploinsufficiency: One functional copy of a gene is not sufficient for normal function. Dominant Negative Effect: A mutant protein interferes with the function of the normal protein. Genetic Mosaicism: Two or more genetically distinct cell lines in one individual due to early embryonic errors. Uniparental Disomy: Both copies of a chromosome come from one parent. Position Effect: A gene’s expression changes due to its location in the genome. Synthetic Lethality: Two mutations that are viable alone but lethal together.
Sex Determination Mechanisms
Genetic Sex Determination: Sex is determined by genes and chromosomes. Chromosomal Sex Determination: Sex is determined by sex chromosomes (XX/XY, ZZ/ZW). Genic Sex Determination: Sex is determined by genes on autosomes, not sex chromosomes. Haplodiploidy: Sex is determined by ploidy level (haploid = male, diploid = female; e.g., bees and ants). Monoecious: Organisms with both male and female reproductive structures. Dioecious: Separate male and female individuals. Chromosomal Systems: XX = female, XY = male (mammals); XX = female, XO = male (grasshoppers); ZZ = male, ZW = female (birds and reptiles). Heterogametic Sex: Produces two types of gametes (XY male/ZW female). Homogametic Sex: Produces one type of gamete (XX female/ZZ male). Pseudoautosomal Regions: Homologous areas on X/Y chromosomes allow pairing during meiosis.
Complementation Test
To determine if two mutations are in the same or different genes: Result: Wild-type offspring: mutations are in different loci. Mutant offspring: mutations are in the same locus. Sex-Influenced Trait: An autosomal trait that is expressed differently in males and females (e.g., male baldness). Sex-Limited Trait: An autosomal trait that is only expressed in one sex (e.g., cow milk production).
Cytoplasmic Inheritance
Traits inherited through organelle genes (mitochondrial/chloroplast); usually maternal (e.g., Leber hereditary optic neuropathy, leaf color in 4 o’clock plants). Genetic Maternal Effect: Offspring phenotype determined by maternal genotype/environment (e.g., snail shell spiral). Genomic Imprinting: Differential expression of a gene based on the parent it comes from (e.g., Igf2 gene, Prader-Willi syndrome, Angelman syndrome); involves DNA methylation (an epigenetic mark). Phenocopy: An environmental factor mimics a genetic trait (e.g., bunny fur color changes). Polygenic Trait: A trait influenced by multiple genes (e.g., height, skin color). Discontinuous Trait: Few distinct phenotypes (e.g., blood type). Continuous Trait: A range of phenotypes due to polygenic inheritance and environmental factors (e.g., height). Pedigree: A diagram of a family’s genetic history used to trace trait inheritance. Proband: The starting individual for a pedigree (indicated by an arrow sign).
Standard Pedigree Symbols:
Square: Male Circle: Female Diamond: Unknown sex Filled: Affected individual Carrier: Bullseye/partial shading Consanguinity: Two parallel lines between partners Adoption: Brackets around symbol. Monozygotic Twins: Connected by a triangle with an extra line. Dizygotic Twins: Connected by a triangle without an extra line.
Modes of Inheritance
Autosomal Recessive: Appears equally in both sexes, often skips generations, more common in consanguineous families. Autosomal Dominant: Appears in every generation, equal frequency in both sexes, affected individuals usually have affected parents. X-Linked Recessive: More common in males, skips generations, no father-to-son transmission. X-Linked Dominant: Affects both sexes (often more females), no male-to-male transmission, affected fathers pass the trait to all daughters. Y-Linked (Holandric): Only males affected, father passes to all sons. Calculating Penetrance: Number of individuals with genotype who express phenotype / (all individuals with genotype) x 100.
Concordance: Percentage of twin pairs sharing a trait / both twins in a pair show the same trait. (# concordant twin pairs / total # of twin pairs x 100) Concordant Trait: Trait present in both twins of a pair. Monozygotic Twins: Identical twins; share 100% of genes. Dizygotic Twins: Fraternal twins; share approximately 50% of genes.