Principles of Inheritance and Variation — Notes

Inheritance is the process by which characters pass from parent to progeny; variation is the degree to which progeny differ from their parents. Gregor Mendel crossed garden peas for seven years (1856–1863), used 14 true-breeding varieties (seven pairs of contrasting traits) and applied statistics to large samples.

Monohybrid cross: tall (TT) × dwarf (tt) → F1 all tall (Tt) → F1 selfed → F2 3 tall : 1 dwarf; genotypes TT : Tt : tt = 1 : 2 : 1. A gene has alternative forms, alleles; homozygous (TT, tt), heterozygous (Tt); genotype vs phenotype. The Punnett square (Reginald Punnett) shows all gamete combinations.

Test cross: a dominant-phenotype organism × the homozygous recessive: all dominant offspring → homozygous; 1 : 1 → heterozygous.

Law of dominance: characters are controlled by discrete paired units (factors); in a dissimilar pair one (dominant) is expressed. Law of segregation: alleles do not blend; the two members of a pair separate during gamete formation, so each gamete gets only one.

Round yellow (RRYY) × wrinkled green (rryy) → F1 round yellow (RrYy). F1 gametes: RY, Ry, rY, ry in equal numbers. F2: 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green.

Law of independent assortment: when two pairs of traits are combined in a hybrid, segregation of one pair is independent of the other. Hence 9 : 3 : 3 : 1 = (3 : 1) × (3 : 1), and probabilities of independent genes multiply.

Dihybrid test cross (RrYy × rryy) → 1 : 1 : 1 : 1.

Mendel published in 1865; the work was rediscovered in 1900 by de Vries, Correns and von Tschermak.

Incomplete dominance: snapdragon (Antirrhinum) red (RR) × white (rr) → pink F1 (Rr); F2 1 red : 2 pink : 1 white (phenotypic = genotypic ratio). Alleles still segregate; this is not blending.

What dominance means: a gene makes a product (often an enzyme). A modified allele may make a normal, a less efficient or a non-functional enzyme, or none. If the unmodified allele alone gives the full phenotype, the modified allele behaves as recessive.

Co-dominance and multiple alleles: ABO blood groups — gene I, alleles Iᴬ, Iᴮ, i; Iᴬ and Iᴮ are co-dominant, both dominant over i.

Pleiotropy: one gene, many effects — phenylketonuria (mental retardation, reduced hair and skin pigmentation); pea starch gene (BB large starch grains and round seeds; bb small grains, wrinkled; Bb round seeds but intermediate grains — dominance depends on the phenotype studied).

Polygenic inheritance: traits controlled by three or more genes with additive effects and environmental influence, giving continuous variation — human skin colour (AABBCC darkest, aabbcc lightest, AaBbCc intermediate) and height.

Sutton and Boveri noted that chromosomes, like Mendel's factors, occur in pairs, segregate at gamete formation and assort independently, and proposed the chromosomal theory of inheritance. T. H. Morgan proved it with Drosophila melanogaster (simple synthetic medium, life cycle of about two weeks, many progeny per mating, clear sex differences, many visible variations).

Morgan's dihybrid crosses with X-linked genes gave far more parental than recombinant types. Linkage: physical association of genes on a chromosome. Recombination: generation of non-parental gene combinations (by crossing over).

• Body colour and eye colour (yellow, white): 1.3 percent recombination — tightly linked.
• Eye colour and wing size (white, miniature): 37.2 percent — loosely linked.

Tightly linked genes show low recombination; loosely linked genes show high recombination. Sturtevant used recombination frequency as a measure of distance to map gene positions on chromosomes.

Henking (1891) named the X body in insect sperm (later the X chromosome).

XO and XY: male heterogamety; ZW: female heterogamety. Humans: 22 pairs of autosomes + XX or XY; ova all carry X; sperms carry X or Y (50 : 50), so the sperm decides the sex.

Honey bee (haplodiploidy): fertilised eggs (32 chromosomes) → females (queen, workers); unfertilised eggs → males (drones, 16 chromosomes) by parthenogenesis. Drones make sperm by mitosis, have no father and so no sons, but have a grandfather and can have grandsons.

A pedigree follows a trait over generations of a family; standard symbols: square (male), circle (female), filled (affected), dot in circle (carrier female), horizontal line (mating), double line (consanguineous mating), Roman numerals for generations.

X-linked recessive disorders (allele on the X chromosome; males hemizygous):

• Haemophilia: a protein in the clotting cascade is affected; a simple cut may bleed non-stop. Transmitted from unaffected carrier females to some sons; affected females are very rare (mother at least a carrier and father haemophilic). Seen in the descendants of Queen Victoria.
• Colour blindness: defect in red or green cone cells; about 8 percent of males and 0.4 percent of females; a daughter is colour blind only if her mother is at least a carrier and her father is colour blind.

Carrier mother × normal father → each son 1/2 chance affected; no daughter affected; half of daughters carriers. Affected father × normal mother → all daughters carriers, no son affected.

Mendelian disorders (single-gene): haemophilia, cystic fibrosis, sickle-cell anaemia, colour blindness, phenylketonuria, thalassemia.

• Sickle-cell anaemia (autosomal recessive): glutamic acid (Glu) replaced by valine (Val) at the sixth position of the β-globin chain, from the single base change GAG → GUG. Disease only in HbˢHbˢ; HbᴬHbˢ are carriers. The changed haemoglobin polymerises at low oxygen, so red cells become sickle-shaped.
• Phenylketonuria (autosomal recessive): the enzyme that converts phenylalanine into tyrosine is missing; phenylalanine and its derivatives build up and damage the brain (mental retardation) and are excreted in urine.
• Thalassemia (autosomal recessive): reduced synthesis of a globin chain, causing anaemia. α: genes HBA1, HBA2 on chromosome 16; β: gene HBB on chromosome 11. Thalassemia is a quantitative problem (too little globin); sickle-cell is qualitative (wrong globin).

Chromosomal disorders: non-disjunction gives aneuploidy; failure of cytokinesis gives polyploidy (common in plants).