Inheritance notes

Basic Terms of Inheritance

A gene is a unit of heredity present at a specific position, or locus, on a chromosome. Different forms of the same gene are called alleles. For example, the allele Y may produce yellow seeds, while y may produce green seeds.

The genetic constitution of an organism is its genotype. The observable appearance or expression of a trait is its phenotype. A dominant allele expresses itself in a heterozygote, whereas a recessive allele is masked by a dominant allele in the heterozygous condition.

• Homozygous means that both alleles of a gene are identical, such as AA or aa.
• Heterozygous means that the two alleles are different, such as Aa.
• A dominant allele is expressed in both homozygous and heterozygous conditions.
• A recessive allele is expressed only when present in the homozygous condition, such as aa.
• A gene or trait that cannot be determined by observing the organism is recessive.
• AaBb is heterozygous at both gene loci and contains dominant alleles for both traits.
• A test cross is the crossing of an individual showing a dominant phenotype with a homozygous recessive individual.
• A disease caused by a defect in a single gene or a pair of genes is called a unifactorial disorder.

Mendel and His Experiments

Gregor Mendel studied inheritance in garden pea, Pisum sativum. He selected pea plants because they have clear contrasting characters, produce many offspring, and can undergo self-pollination as well as cross-pollination.

Mendel began with true-breeding plants. A cross between plants differing in one character is a monohybrid cross. A cross in which two characters are followed at the same time is a dihybrid cross.

• In a monohybrid cross, one pair of contrasting characters is studied.
• In a dihybrid cross, two pairs of contrasting characters are studied simultaneously.
• When tall pea plants were crossed with dwarf plants, all F1 plants were tall.
• The appearance of tallness in F1 shows that tallness is dominant over dwarfness.
• The parental generation is represented by P, the first filial generation by F1, and the second filial generation by F2.
• The F1 generation is produced by crossing the parental plants.
• The F2 generation is produced by self-crossing or intercrossing F1 individuals.
• Mendel’s factors are now called genes, and alternative forms of a gene are called alleles.

Mendel’s Laws of Inheritance

The law of dominance states that when two contrasting alleles occur together in a heterozygote, one allele expresses itself and is dominant, while the other is masked and is recessive. In a cross between TT and tt, all F1 offspring are Tt and tall.

The law of segregation states that the two alleles of a gene separate during gamete formation. Each gamete receives only one allele of the pair. At fertilisation, the alleles unite again.

The law of independent assortment states that alleles of different genes assort independently during gamete formation, provided the genes are not linked. This law explains the combinations seen in a dihybrid cross.

• A monohybrid F2 phenotypic ratio is 3 dominant : 1 recessive.
• A monohybrid F2 genotypic ratio is 1 homozygous dominant : 2 heterozygous : 1 homozygous recessive.
• A heterozygous yellow seed has genotype Yy.
• A test cross Yy × yy produces 50% yellow seeds and 50% green seeds.
• A dihybrid cross follows two characters at the same time.
• The usual Mendelian dihybrid F2 phenotypic ratio is 9 : 3 : 3 : 1.
• In a dihybrid F2 generation, the genotype rryy occurs in 1 out of 16 offspring, or 1/16.
• Independent assortment does not apply in the usual way when genes are closely linked on the same chromosome.

Multiple Alleles and Human Blood Groups

A gene may have more than two alleles in a population, although one individual carries only two alleles at a time. This condition is called multiple allelism. The ABO blood group system is controlled by the gene I, which has three alleles: IA, IB and i.

IA and IB are codominant with each other. Both are expressed in a person having genotype IAIB. The allele i is recessive to both IA and IB. Therefore, the ABO system has six possible genotypes and four phenotypes.

• The six ABO genotypes are IAIA, IAi, IBIB, IBi, IAIB and ii.
• Blood group A has genotype IAIA or IAi.
• Blood group B has genotype IBIB or IBi.
• Blood group AB has genotype IAIB.
• Blood group O has genotype ii.
• The four ABO phenotypes are A, B, AB and O.
• Parents with blood groups A and B can have a child with blood group AB if their genotypes provide IA and IB.
• A child with blood group O must receive the recessive i allele from both parents.
• A man with blood group AB and a woman with blood group A cannot have a child with blood group O, because the AB parent has no i allele.

Rh Factor and Other Human Traits

The Rh blood group is determined mainly by the presence or absence of the Rh antigen. Rh positive is dominant over Rh negative. A person with at least one dominant Rh allele is Rh positive, while the homozygous recessive condition is Rh negative.

Some human traits do not follow simple Mendelian dominance. A sex-influenced trait is controlled by autosomal genes but is expressed differently in males and females. Pattern baldness is a standard example.

• Rh positive is genetically dominant over Rh negative.
• Pattern baldness is a sex-influenced trait.
• Sex-influenced traits are controlled by genes on autosomes, not necessarily by genes on sex chromosomes.
• Human skin colour is a quantitative trait controlled by several gene pairs.
• Human skin colour is described in FSc genetics as being controlled by three to six gene pairs.
• Quantitative traits show continuous variation rather than only two sharply separated forms.
• The combined effect of several genes produces the range of skin colours in humans.
• Epilepsy is not classified as a genetic disorder in the stated classification, although some forms may have genetic causes.

Gene Linkage and Crossing Over

Genes located on the same chromosome are called linked genes. Because they lie on the same chromosome, they tend to pass together into gametes. This tendency is called linkage and it does not follow independent assortment completely.

During meiosis, homologous chromosomes pair during prophase I. Non-sister chromatids may exchange corresponding segments. This exchange is called crossing over and produces new allele combinations, called recombinants.

• Linked genes are present on the same chromosome.
• The group of genes present on one chromosome is called a linkage group.
• Genes that remain together in offspring are called parental combinations.
• New combinations produced by exchange between homologous chromosomes are called recombinant combinations.
• Crossing over occurs between non-sister chromatids of homologous chromosomes during prophase I of meiosis.
• The frequency of crossing over is related to the distance between genes. Greater distance generally gives a greater recombination frequency.
• Morgan’s linkage experiment with fruit flies produced about 37% recombinants in the stated F2 mating.
• Complete linkage produces only parental combinations, while incomplete linkage produces both parental and recombinant combinations.
• Linkage limits independent assortment, whereas crossing over increases genetic variation.

Sex Determination and Sex-Linked Genes

In humans, females usually have XX sex chromosomes and males usually have XY sex chromosomes. All eggs carry an X chromosome. Sperm carry either X or Y, so the sperm determines the chromosomal sex of the child.

Genes located on sex chromosomes are called sex-linked genes. X-linked genes are present on the X chromosome. A male has only one X chromosome, so a recessive allele on his X chromosome is expressed because there is no corresponding allele on the Y chromosome.

• In humans, the female is XX and the male is XY.
• The male produces two types of sperm, X-bearing and Y-bearing, in approximately equal numbers.
• The female produces eggs carrying only the X chromosome.
• The chance of a son in each pregnancy is 50%, regardless of the sex of previous children.
• The chance of a sixth child being a son remains 50% after five daughters.
• In the XO-XX system, males are XO and females are XX.
• The XO-XX type of sex determination is found in the Protenor bug.
• In a heterozygous male fruit fly for an X-linked gene, the male-specific chromosome enters eggs in the proportion 1 : 1 when the relevant sex chromosomes are considered in the cross.

X-Linked Recessive Inheritance

An X-linked recessive trait is caused by a recessive allele located on the X chromosome. Such traits are more common in males because a male has only one X chromosome. A female generally expresses the trait only when she receives the recessive allele on both X chromosomes.

A carrier female has one normal allele and one recessive disease allele. She usually does not show the trait but can transmit the allele to her sons and daughters. Affected males transmit their X chromosome to all daughters and their Y chromosome to all sons.

• The gene for colour blindness in males is present on the X chromosome.
• Colour blindness is more common in males than females because the gene is located on a sex chromosome and males have only one X chromosome.
• Haemophilia A, haemophilia B, colour blindness and testicular feminisation are examples of X-linked recessive traits.
• A colour-blind father passes his affected X chromosome to all daughters, but he does not pass it to his sons.
• A colour-blind girl can be born only when her father is colour blind and her mother is at least a carrier.
• A haemophilic man can pass the allele to his grandson through his daughter, because his daughter receives his affected X chromosome.
• The sons of a carrier mother have a 50% chance of receiving the affected X chromosome.
• A carrier daughter can result when an affected father passes his affected X chromosome to a daughter and the mother provides a normal X chromosome.

Examples of Sex-Linked Traits and Genetic Risk

Colour vision depends on cone cells and their opsin pigments. A defect in an X-linked opsin gene can produce colour blindness. The term deuteranomalous refers to a partially functional opsin associated with green colour vision.

Cystic fibrosis is a recessive disorder caused by mutation in a gene on an autosome. Risk calculations depend on the genotypes of the parents and the information available about unaffected relatives.

• The partially functional opsin for green colour is called deuteranomalous.
• Cystic fibrosis is inherited as an autosomal recessive disorder.
• If an unaffected sister has an affected brother in a family where both parents are carriers, her chance of being a carrier is 2/3.
• If Kathy has a 2/3 chance of being a carrier and her husband is assumed to contribute a normal allele, the chance of her child inheriting the cystic fibrosis allele from her is 2/3 × 1/2 = 1/3.
• For a child to have cystic fibrosis, the child must receive a disease allele from both parents.
• A genetic disorder may result from a mutation in one gene or from changes involving more than one gene or chromosome.
• Genetic counselling uses family history and probability to estimate the risk of inherited disorders.