Inheritance

📚The biology

Gametes and zygotes

In every eukaryote with a sexual life cycle, inheritance follows the same pattern. Each parent produces haploid gametes by meiosis, carrying one copy of each gene. At fertilization two gametes fuse to form a diploid zygote, which therefore has two copies of each autosomal gene — one from each parent. (Autosomes are all the chromosomes other than the sex chromosomes.)

Genetic crosses in flowering plants

Pollen contains the male gametes and the female gametes are in ovules inside the ovary, so a cross is made by pollination: pollen from one chosen plant is transferred to the stigma of another. Plants such as peas produce both male and female gametes on the same plant, so they can self-pollinate and therefore self-fertilize. To make a controlled cross, the anthers of the female parent are removed before they release pollen, and the flower is covered to prevent stray pollen arriving.

Genetic crosses are widely used to breed new varieties of crop and ornamental plants.

Genes, alleles and genotype

A gene is a heritable factor that influences a characteristic, found at a particular position (locus) on a chromosome. Alleles are different versions of the same gene, differing slightly in base sequence. The genotype is the combination of alleles an organism has for a gene.

Phenotype

The phenotype is the set of observable traits of an organism, resulting from its genotype and environmental factors. In humans:

Dominant and recessive alleles

A dominant allele affects the phenotype whenever it is present, in one or two copies. A recessive allele only affects the phenotype when no dominant allele is present, that is, in the homozygous recessive. Dominant alleles are written with a capital letter, recessive with the lower-case version of the same letter.

Why does a heterozygote look the same as a homozygous dominant? Usually the dominant allele codes for a functional protein such as an enzyme, and the recessive allele codes for a non-functional version or none at all. One copy of the dominant allele produces enough functional protein to give the full phenotype, so TT and Tt look identical.

Phenotypic plasticity

Phenotypic plasticity is the capacity of an organism to develop traits suited to the environment it experiences, by varying patterns of gene expression. It is not due to a change in genotype, and the changes may be reversible during an individual’s life. Examples: human skin tanning with sun exposure; muscles enlarging with exercise; some plants producing thinner, broader leaves in shade.

Phenylketonuria

Phenylketonuria (PKU) is a recessive genetic condition caused by a mutation in an autosomal gene coding for the enzyme that converts the amino acid phenylalanine to tyrosine. Only people homozygous for the recessive allele are affected: they cannot make the functional enzyme, phenylalanine accumulates in the blood and damages the developing brain. Heterozygous carriers have one working allele and are unaffected. Newborns are screened, and affected children follow a low-phenylalanine diet, which prevents brain damage.

SNPs and multiple alleles

Each base substitution that becomes established in a population is a single-nucleotide polymorphism (D1.3). Over time, many different alleles of a gene can accumulate. Any number of alleles of a gene can exist in the gene pool of a population, but an individual diploid organism inherits only two.

ABO blood groups: multiple alleles

The ABO blood group gene has three alleles: I^A, I^B and i. I^A and I^B are codominant with each other, and both are dominant to i.

Codominance and incomplete dominance

Sex determination and sex chromosomes

Humans have 22 pairs of autosomes and one pair of sex chromosomes: typical female bodies have XX and typical male bodies XY. All eggs carry an X chromosome; sperm carry either an X or a Y. So the sex chromosome in the sperm determines whether the zygote develops certain male-typical physical characteristics (Y, due to a gene on the Y chromosome that triggers development of testes) or female-typical ones (X). The ratio is expected to be 1 : 1.

The X chromosome is much larger and carries far more genes (over 800 coding for proteins) than the Y chromosome (under 100). Genes carried on the X are sex-linked. Because males have only one X, any recessive allele on it is expressed.

Haemophilia

Haemophilia is a sex-linked recessive disorder in which blood fails to clot properly, because a gene on the X chromosome coding for a clotting factor is faulty. Alleles on the X chromosome are shown as superscripts on an uppercase X: X^H (normal) and X^h (haemophilia).

Haemophilia is far more common in males. An affected male cannot pass it to his sons (they get his Y) but all his daughters will be carriers.

Pedigree charts

A pedigree chart shows the inheritance of a condition in a family: circles for females, squares for males, shaded for affected, horizontal lines joining parents, vertical lines to children. Reasoning from the chart:

• Recessive: two unaffected parents have an affected child — both parents must be carriers.
• Dominant: two affected parents have an unaffected child; and every affected person has at least one affected parent.
• Sex-linked recessive: mostly affected males; affected sons of unaffected (carrier) mothers; never passed from father to son.

This uses both kinds of reasoning. Seeing a pattern in some families and generalizing (“this condition is recessive”) is inductive reasoning. Then applying that conclusion to deduce the genotypes of particular individuals in the chart is deductive reasoning.

Pedigrees also show why many societies prohibit marriage between close relatives. Relatives are more likely to carry the same rare recessive alleles, inherited from a common ancestor, so their children have a higher probability of being homozygous recessive for a harmful condition.

Continuous variation

Continuous data are summarized with measures of central tendency: the mean (sum of values ÷ number of values), the median (middle value when ordered) and the mode (most frequent value).

Box-and-whisker plots

A box-and-whisker plot displays the distribution of a continuous variable, such as student height, showing six features:

The interquartile range (IQR) = Q3 − Q1. A data point is an outlier if it is more than 1.5 × IQR above Q3 or below Q1.

Segregation and independent assortment AHL

The movements of chromosomes in meiosis explain the outcomes of crosses:

• Segregation: the two alleles of a gene, on a pair of homologous chromosomes, separate into different gametes when homologues separate in meiosis I.
• Independent assortment: for two genes on different chromosomes (unlinked), the orientation of one bivalent at metaphase I is independent of the other. So the allele a gamete receives for one gene does not affect which allele it receives for the other. An individual AaBb produces four types of gamete — AB, Ab, aB, ab — in equal proportions.

Dihybrid crosses AHL

A dihybrid cross follows two genes at once. With two unlinked autosomal genes:

The 9:3:3:1 and 1:1:1:1 ratios depend on what has been called Mendel’s second law, independent assortment. This “law” only applies if the genes are on different chromosomes, or so far apart on one chromosome that crossing over separates them half the time (a 50% recombination rate). Like other biological “laws”, it has exceptions.

Gene loci in databases AHL

Online databases such as those of the NCBI and Ensembl give the locus (chromosome and position) of each human gene and the polypeptide it codes for. Exploring them, you can find pairs of genes on different chromosomes, which will assort independently, and pairs close together on the same chromosome, which will tend to be inherited together.

Autosomal gene linkage AHL

Linked genes are genes located on the same chromosome. They do not assort independently, because they tend to be inherited together: they move as one unit when the chromosome moves in meiosis. The closer together they are, the more strongly linked.

When showing linked genes, write the alleles alongside vertical lines representing the two homologous chromosomes, so that it is clear which alleles are on the same chromosome. For example, a heterozygote with A and B on one chromosome and a and b on the other is shown with A above B on the left line and a above b on the right line.

Recombinants AHL

In a cross between an individual heterozygous for both genes and one homozygous recessive for both:

• If the genes are unlinked, the heterozygote produces four gamete types equally, and offspring appear in a 1:1:1:1 ratio.
• If the genes are linked, the heterozygote mostly produces gametes with the parental combinations of alleles (AB and ab in the example above). Only when crossing over occurs between the two loci are recombinant gametes (Ab and aB) produced, and these are less common.

Recombinants are gametes, genotypes or phenotypes with a combination of alleles different from either parent. In a test cross with linked genes, the two parental phenotypes are most common and the two recombinant phenotypes are least common.

Chi-squared test on dihybrid data AHL

Observed results never match expected ratios exactly, because of chance. The chi-squared test decides whether a difference between observed and expected results is small enough to be due to chance or is statistically significant.

1. State a null hypothesis: there is no significant difference between observed and expected results (e.g. the genes are unlinked and assort independently). The alternative hypothesis is that there is a significant difference.
2. Calculate expected numbers from the predicted ratio and the total.
3. Calculate \( \chi^{2} = \sum \dfrac{(O - E)^{2}}{E} \).
4. Degrees of freedom = number of categories − 1 (for four phenotypes, 3).
5. Compare with the critical value at the p = 0.05 significance level (7.815 for 3 degrees of freedom). If \( \chi^{2} \) is less, accept the null hypothesis; if it is greater, reject it.

The F2 generation is a sample used to represent all possible offspring. p = 0.05 means there is a 5% probability that a difference this large would arise by chance alone if the null hypothesis were true.