Meiosis & Genetics

Mitosis makes two identical copies of a cell. But sex cells — eggs and sperm — cannot be identical copies of normal body cells. If they were, fertilisation would double the chromosome number with every generation: 46 → 92 → 184... Meiosis solves this problem by halving the chromosome number. It produces cells with only 23 chromosomes (one from each pair) — called haploid cells. When two haploid sex cells fuse at fertilisation, the normal diploid number of 46 is restored. Diploid vs haploid — the key vocabulary: - Diploid (2n) — the full set of chromosomes, in pairs. Humans are diploid: 2n = 46 (23 pairs). - Haploid (n) — half the chromosome number. Human sex cells: n = 23. - Homologous chromosomes — the two chromosomes in each pair. One came from your mother, one from your father. They carry the same genes but may have different versions (alleles) of those genes. The key differences between mitosis and meiosis: | Feature | Mitosis | Meiosis | |---|---|---| | Purpose | Growth & repair | Making sex cells | | Divisions | 1 | 2 | | Daughter cells | 2 | 4 | | Chromosome number | Same (46) | Halved (23) | | Genetic result | Identical | Genetically unique |

Meiosis consists of two rounds of division: Meiosis I and Meiosis II. Meiosis I — separating homologous pairs: This is the reduction division — where the chromosome number is halved. The stages look similar to mitosis (Prophase I, Metaphase I, Anaphase I, Telophase I), but with one crucial difference: crossing over (recombination) happens during Prophase I. Crossing over — the key to genetic diversity: During Prophase I, homologous chromosomes pair up tightly — one from mum, one from dad. While paired, they physically swap sections of DNA with each other. This shuffles the genetic information so that the chromosome you pass on to your child is a unique mixture of your maternal and paternal DNA — not purely one or the other. The positions where crossing over happens are called chiasmata (singular: chiasma). Every pair of homologous chromosomes usually has at least one or two crossovers. During Anaphase I, the homologous pairs are pulled apart (not the sister chromatids — that happens in Meiosis II). Each pole gets one member of each pair. Result of Meiosis I: two cells, each with 23 chromosomes — but each chromosome is still made of two sister chromatids. Meiosis II — separating sister chromatids: This is essentially mitosis of the two haploid cells produced in Meiosis I. Sister chromatids are separated, producing four haploid cells. Result: 4 haploid cells (n = 23), all genetically unique from each other and from the original cell. In males: meiosis produces 4 functional sperm cells. In females: meiosis is unequal — one large egg cell and small "polar bodies" that are discarded. This gives the egg cell almost all the cytoplasm (which the developing embryo will need).

A gene is a section of DNA that codes for a particular protein or trait. Humans have roughly 20,000–25,000 genes spread across the 23 pairs of chromosomes. Because you have two copies of every chromosome (one from each parent), you have two copies (alleles) of most genes — one maternal, one paternal. Alleles — different versions of the same gene: For most genes, both copies are the same. But sometimes the two alleles are different. For example, the gene for eye colour might have a "brown" allele on the maternal chromosome and a "blue" allele on the paternal chromosome. Dominant vs recessive: - A dominant allele produces its trait whenever it is present — even if only one copy is present. - A recessive allele only produces its trait when both copies are the recessive version (no dominant allele to override it). Capital letters = dominant (B = brown eyes); lowercase = recessive (b = blue eyes). Genotype and phenotype: - Genotype — the actual alleles a person has (e.g. Bb or BB or bb) - Phenotype — the observable trait (e.g. brown eyes or blue eyes) If a person has one dominant and one recessive allele (Bb), they are heterozygous — and will show the dominant phenotype (brown eyes) but are a carrier of the recessive allele. If both alleles are the same (BB or bb), they are homozygous. A classic example — cystic fibrosis: Cystic fibrosis (CF) is caused by a recessive mutation in the CFTR gene. To have CF, you must inherit two faulty copies — one from each parent. Parents who are carriers (Cf) appear healthy but have a 1 in 4 chance of having an affected child with each pregnancy. This is why genetic counselling and carrier testing matter for families with a history of CF.

Of the 23 pairs of chromosomes, 22 pairs are autosomes (identical in males and females). The 23rd pair are the sex chromosomes: - Females: XX — two X chromosomes - Males: XY — one X and one (much smaller) Y chromosome The Y chromosome carries the SRY gene that triggers male development. Without it, the embryo follows a female developmental pathway by default. Why sex is determined by sperm, not egg: Every egg carries an X chromosome (that is the only option from an XX female). Sperm can carry either X or Y. If an X sperm fertilises the egg → XX (female). If a Y sperm fertilises the egg → XY (male). So the father's sperm determines the sex of the child — not the mother, despite many historical misconceptions. X-linked (sex-linked) traits: Some genes are carried on the X chromosome but have no corresponding gene on the Y. Males (XY) only have one copy of these genes — so if that one copy is faulty, there is no second copy to compensate. This is why X-linked recessive conditions affect males far more than females: - Haemophilia — a bleeding disorder caused by a faulty clotting factor gene on the X chromosome. Males with one faulty X have haemophilia. Females need two faulty copies (very rare). - Red-green colour blindness — affects ~8% of males but only ~0.5% of females for the same reason. - Duchenne muscular dystrophy — caused by a faulty dystrophin gene on the X chromosome. Affects 1 in 3,500 males; females are usually unaffected carriers. Mitochondrial inheritance: Mitochondria have their own small circular DNA (inherited from the original bacterial ancestor). Crucially, mitochondria are inherited exclusively from the mother — the egg contributes all the mitochondria to the embryo; sperm mitochondria are destroyed after fertilisation. Mitochondrial DNA diseases (like MELAS, MERRF) are therefore inherited purely through the maternal line.

A mutation is any permanent change in the DNA sequence. Mutations are the ultimate source of all genetic variation — they are how evolution works. But in individuals, mutations can cause disease. Types of mutation: Point mutations — single base changes: - Substitution — one base is replaced by another. Can be silent (no change to the protein), missense (changes one amino acid), or nonsense (creates a stop codon, truncating the protein). Sickle cell anaemia is caused by a single substitution changing one amino acid in haemoglobin (glutamate → valine) — making red blood cells deform into a sickle shape. - Insertion or deletion — a base is added or removed. This causes a frameshift mutation — the entire reading frame shifts, usually making a non-functional protein. Cystic fibrosis (the most common CF mutation, ΔF508) involves a deletion of 3 bases. Chromosomal mutations — larger scale: - Deletion — a chunk of chromosome is lost - Duplication — a segment is copied twice - Translocation — a piece of one chromosome attaches to another. The Philadelphia chromosome (a translocation between chromosomes 9 and 22) creates the BCR-ABL fusion gene that drives chronic myeloid leukaemia (CML). The drug imatinib (Gleevec) specifically targets this protein — a landmark in targeted cancer therapy. Causes of mutations: - Spontaneous — errors in DNA replication (~1 error per billion bases, before repair) - Mutagens — UV radiation (causes thymine dimers), ionising radiation, certain chemicals (tobacco carcinogens, asbestos) - Viruses — some viruses integrate their DNA into the host genome (HPV and cervical cancer; HBV/HCV and liver cancer) Most mutations are repaired by the cell's DNA repair machinery. Those that escape repair and occur in critical genes can contribute to cancer or inherited disease.