Monohybrid inheritance and genetic diagrams

The words, used precisely

A gene is a length of DNA coding for a polypeptide or a functional RNA. An allele is one of the alternative versions of that gene. The locus is the fixed position on the chromosome where the gene sits, the same position on both members of a homologous pair, which is why you carry two alleles of every autosomal gene.

Genotype

The alleles an organism carries, for the gene or genes under discussion.

Phenotype

The observable characteristics of an organism, produced by its genotype interacting with its environment.

Homozygous

Carrying two identical alleles of a gene.

Heterozygous

Carrying two different alleles of a gene.

Dominant

An allele whose effect appears in the phenotype even when only one copy is present.

Recessive

An allele whose effect appears only when no dominant allele is present: in a homozygote, or in a male for a gene on the X chromosome.

Carrier

An individual heterozygous for a recessive allele, so not showing the characteristic but able to pass the allele on.

F1 and F2

The first filial generation, the offspring of the original parental cross, and the second, the offspring of F1 individuals crossed with each other.

Test cross

A cross between an organism of dominant phenotype and a homozygous recessive, to find whether the first is homozygous or heterozygous.

Two conventions apply to allele symbols. Choose a letter whose capital and lower-case forms look different, since T and t are distinguishable in handwriting where S and s and C and c are not, and use the same letter for both alleles of a gene rather than one letter for the dominant and a different letter for the recessive. Define the symbols before using them: a line reading 'let T be the allele for tall and t the allele for dwarf' is part of a complete genetic diagram.

The environment appears in the definition of phenotype because it contributes to it. Two genetically identical plants grown in different light reach different heights; monozygotic twins differ in mass. Where a question asks why two organisms of the same genotype differ in appearance, state the environmental influence on the characteristic concerned.

The layout of a genetic diagram

A complete genetic diagram defines the allele symbols and shows parental phenotypes and genotypes, gametes, offspring genotypes, and the expected phenotype ratio. A Punnett square displays the possible fertilisations. The ratio is a probability distribution and is approached most closely when many offspring are produced.

Describe the drawing

A monohybrid cross written out as a labelled column of stages. A key at the top defines capital T as the allele for tall and lower-case t as the allele for dwarf. The parental phenotypes are two tall plants; their genotypes are capital T lower-case t and capital T lower-case t; each parent's two gametes are drawn inside circles, carrying capital T or lower-case t. A two-by-two Punnett square below combines them, with one parent's gametes along the top and the other's down the side, and its four cells read capital T capital T, capital T lower-case t, capital T lower-case t and lower-case t lower-case t. The offspring genotype ratio one to two to one and phenotype ratio three tall to one dwarf are written underneath.

The order is: parental phenotypes, parental genotypes, gametes, offspring genotypes, offspring phenotypes and ratio. Setting the offspring out in a Punnett square rather than as crossed lines makes each fertilisation explicit. Read the ratio from the square rather than recalling it, since a remembered ratio belongs to a particular cross.

Three crosses cover almost everything at this level. Two heterozygotes give 1 TT : 2 Tt : 1 tt, and so 3 tall : 1 dwarf. A heterozygote crossed with a homozygous recessive gives 1 Tt : 1 tt, and so 1 : 1. A homozygous dominant crossed with anything gives all dominant offspring, because every offspring receives at least one dominant allele. The first of those separates the two ratios: 1 : 2 : 1 by genotype against 3 : 1 by phenotype.

The second cross has a name and a purpose. A test cross pairs an organism showing the dominant phenotype with a homozygous recessive, to find out whether the first one is homozygous or heterozygous. If any offspring shows the recessive phenotype, the unknown parent must have carried a recessive allele and is heterozygous. If a large number of offspring all show the dominant phenotype, the unknown parent is very probably homozygous, and 'very probably' is the accurate word, because a heterozygote could produce eight dominant offspring in a row by chance about once in every 256 attempts.

Codominance, incomplete dominance and multiple alleles

Complete dominance is common but is not the only relation between two alleles. Two others occur. Where two alleles are codominant, both are expressed in the heterozygote and the phenotype shows both fully, side by side. Where dominance is incomplete, the heterozygote shows a blended, intermediate phenotype instead. In either case neither allele is subordinate, so they cannot be written as a capital and a lower-case letter; the convention is a capital letter for the gene with a raised letter for each allele, such as C^R and C^W.

Snapdragon flower colour is the standard example of incomplete dominance. C^RC^R plants are red, C^WC^W are white, and C^RC^W are pink, a blend rather than both colours at once. Roan cattle are the clean example of codominance: red hairs and white hairs sit side by side in the same coat, each fully expressed.

Cross two heterozygotes in either case and the offspring come out 1 : 2 : 1, because the heterozygote is distinguishable and the phenotype ratio is the genotype ratio. That means the ratio alone cannot tell the two relations apart; look at the heterozygote itself. A blend points to incomplete dominance, both phenotypes at once to codominance. Some textbooks file both cases under codominance, and if your board does, use its wording in the exam.

Human sickle-cell anaemia works the same way at the molecular level. The gene is HBB, which codes for the beta-globin polypeptide of haemoglobin, and someone with genotype Hb^AHb^S makes both normal haemoglobin and sickle haemoglobin, so both alleles are expressed and the alleles are codominant. Whether the person is described as having the disease is a separate question from which alleles are expressed: heterozygotes express both polypeptides but do not usually show the clinical condition.

A gene can also have more than two alleles in the population, which is called having multiple alleles. Any one individual still carries only two, because there are only two copies of the locus, one on each chromosome of the homologous pair. The human ABO blood group system is the example every board uses, and it combines multiple alleles with codominance in one gene.

Describe the drawing

Six genotypes listed down the left, each with an arrow across to the blood group it produces and the antigen on the red cell. I A with I A and I A with I O both give group A carrying antigen A; I B with I B and I B with I O both give group B carrying antigen B; I A with I B gives group AB carrying both antigens; I O with I O gives group O with no antigen. A line above states that I A and I B are codominant and I O is recessive to both.

The three alleles are I^A, I^B and I^O. I^A codes for antigen A on the red cell surface and I^B for antigen B; I^O codes for neither. I^A and I^B are codominant with each other, and both are dominant to I^O. Some textbooks and some boards write the third allele as a lower-case i rather than I^O; the biology is identical, so use whichever notation your specification uses and define it at the top of your answer.

Genes on the X chromosome

The sex chromosomes break the symmetry the rest of genetics relies on. In humans a female is XX and a male XY, and the Y is much smaller than the X and carries far fewer genes. A gene present on the X with no equivalent on the Y is sex-linked. A female carries two alleles of it and can be homozygous or heterozygous; a male carries one, and whichever allele he has is expressed, because there is no second copy to mask it.

That asymmetry accounts for the inheritance pattern. Recessive sex-linked conditions such as haemophilia A, red-green colour blindness and Duchenne muscular dystrophy are far more common in males, because a male needs only one recessive allele to show the condition while a female needs two. A female heterozygote is a carrier and shows nothing.

Haemophilia A is the one to know by its gene. The gene is F8, it sits on the X chromosome, and it codes for factor VIII, one of the proteins in the cascade that converts fibrinogen to fibrin and clots blood. The recessive allele produces a version of factor VIII that does not work, or too little of it, so the cascade stalls, clotting is slow and bleeding into joints and muscles follows minor injuries. A person carrying one working copy of F8 makes enough functional factor VIII to clot normally, which is exactly why the allele is recessive.

Describe the drawing

A two-by-two Punnett square for a sex-linked cross. The mother's two gametes, X carrying the dominant allele and X carrying the recessive allele, run down the side; the father's, X carrying the dominant allele and Y, run along the top. The four cells read: an unaffected girl, an unaffected boy, a carrier girl, and an affected boy, the last one filled in coral. Text beneath notes that this is one child in four but one son in two.

Write the allele as a raised letter on the X, as X^H and X^h, and include the Y, so a male genotype reads X^hY rather than a bare h. The X and Y are what show the gene to be sex-linked; without them the diagram does not distinguish sex linkage from autosomal inheritance.

Two rules follow from tracing the alleles through a family. A father passes his X to every daughter and never to a son, so an affected father cannot pass a sex-linked condition to his sons at all, and every one of his daughters is at least a carrier. A son gets his single X from his mother, so an affected son inherited the allele from his mother, whatever the father's phenotype. Those two sentences answer most pedigree questions on the topic before you draw anything.

Pedigree diagrams

Nobody can set up a test cross between two people, so human genetics works from the families that already exist. A pedigree diagram, or family tree, records one characteristic through several generations of a family, and it is the genetic diagram used where breeding experiments are impossible.

Questions on one ask for one of three things: whether the allele is dominant or recessive, whether the gene is on an autosome or on the X chromosome, and the genotype of one person or the probability for a child not yet born.

The symbols are standard. A square is a male and a circle a female. A shaded symbol is a person who shows the characteristic, described as affected, and an open symbol is a person who does not.

A horizontal line joining a square and a circle marks a couple who have had children together. A vertical line drops from the middle of it to a second horizontal line, and each child hangs from that line, eldest on the left.

Generations are numbered down the page in Roman numerals, and the people in each generation are numbered across it from left to right, so II-3 is the third person in the second generation. Someone who married into the family is drawn on the same row as their partner, with no line up to the generation above. Some diagrams mark a known carrier with a half-shaded symbol or a dot; an exam paper always prints a key, so read it before reading the tree.

Describe the drawing

A family tree in three rows, numbered I, II and III down the left. In generation I an unaffected man, 1, and an unaffected woman, 2, are joined by a horizontal line, and a vertical line drops from it to their three children in generation II: an unaffected son, 1, an affected daughter, 2, drawn as a filled circle, and an unaffected son, 3. Son 3 is joined to an unaffected woman, 4, who married into the family, and their three children in generation III are an unaffected daughter, 1, an affected son, 2, drawn as a filled square, and an unaffected daughter, 3. A key at the bottom shows squares as males, circles as females and filled symbols as people with cystic fibrosis.

To draw a pedigree from a written account, give each generation its own row, put each couple side by side with the line between them, hang the children in birth order, shade only the people the account says are affected, and add a key. Number the generations and the individuals so that every person in an answer can be named.

The deduction runs in a fixed order. The first question is dominant or recessive. Look for two unaffected parents with an affected child. The child received an allele for the characteristic from each parent, yet neither parent shows it, so the allele was hidden in both: it is recessive, and both parents are heterozygous.

The opposite pattern, two affected parents with an unaffected child, shows the allele is dominant, because each parent must have carried a recessive allele to pass on. If neither pattern appears in the tree, the question cannot be settled from it; say which is more likely and why.

The second question is autosomal or sex-linked, and it rests on the two rules from the section above: a father passes his X to every daughter and to no son, and a son's single X comes from his mother.

For a recessive allele, an affected daughter with an unaffected father rules out the X chromosome, since her father would have had to give her an X carrying the allele and would then have shown the condition himself. An affected mother with an unaffected son rules it out too, because both of her X chromosomes carry the allele and the son's only X came from her.

For a dominant allele, an affected father with an unaffected daughter rules out the X. A son who can only have received the allele from his father, such as the affected son of an affected father and an unaffected mother when the allele is dominant, shows the gene is autosomal, because a son receives his father's Y and not his X. With a recessive allele, an affected father and an affected son prove nothing about the X on their own, since the mother may be a carrier. A tree in which mostly males are affected suggests X-linked recessive inheritance but does not prove it.

Describe the drawing

Three small family trees side by side, each a father and a mother joined by a line with one child below. Left: both parents unaffected and a son affected, labelled recessive. Middle: both parents affected, drawn filled, and a daughter unaffected, labelled dominant. Right: an unaffected father and mother with an affected daughter, labelled not X-linked, because a father passes his X to every daughter and an unaffected father has no recessive allele on it to give.

The third step is the genotypes, starting with the people whose genotype is fixed by what they show. For a recessive condition every affected person is homozygous recessive. An unaffected parent of an affected child must be heterozygous, and so must an unaffected child of an affected parent. The people left over could be either, and are written that way, as FF or Ff.

For the unaffected child of two carriers there is a number to put on it. Of the four equally likely outcomes of Ff × Ff, one is ff, and that one is ruled out because the child is unaffected. That leaves FF, Ff and fF, so the probability that the child is a carrier is 2/3, not 1/2.

Pedigree diagram

A family tree showing how one characteristic is inherited through several generations, with males as squares, females as circles and affected people shaded.

Affected

Showing the characteristic a pedigree follows; drawn as a shaded symbol.

Autosomal

Carried on an autosome, any chromosome other than the sex chromosomes, so inherited in the same way by sons and daughters.

Named genes and the proteins they code for

The crosses above use letters chosen for convenience. Cambridge International also requires the gene, the protein it codes for, and the effect of the altered allele on that protein.

A phenotype can result from one or many genes and may also be influenced by the environment. Where a named example is used, explain the relevant gene product and how the allele changes its amount or function; do not present every phenotype as a single protein that either works or fails.

Oculocutaneous albinism type 1 is one such example. The gene is TYR, and it codes for tyrosinase, the enzyme that catalyses the first step in converting the amino acid tyrosine into the pigment melanin. The recessive allele carries a mutation that gives a non-functional enzyme, so a person homozygous for it makes little or no melanin and has white or very pale hair, pale skin and pale irises. A heterozygote has one working copy of TYR, makes tyrosinase from it and is normally pigmented, which is why the allele is recessive: one functional copy of an enzyme gene is usually enough. Albinism as a whole is genetically heterogeneous, and other genes give other forms of it, so name the type rather than treating TYR as the single cause.

Sickle cell anaemia gives a different relation between the alleles. The gene is HBB, coding for the beta-globin polypeptide of haemoglobin. A single base substitution changes one codon, so valine appears at the sixth amino acid position where glutamic acid should be, and the resulting haemoglobin S sticks to itself when it gives up its oxygen, forming long fibres that pull the red cell out of shape. A heterozygote makes both polypeptides, because both alleles are transcribed and translated, so both are expressed and the alleles are codominant rather than one being masked.

Haemophilia A is set out above: the gene is F8 on the X chromosome, the protein is factor VIII, and a non-functional version slows the clotting cascade. Its position on the X, rather than the chemistry of the protein, is what gives it a different pattern of inheritance from the other three.

Huntington's disease differs from the others in the kind of mutation involved. The gene is HTT and the protein is huntingtin. The mutation is not a substitution but an expansion: a short sequence of three bases, CAG, is repeated far more times than usual, so the protein carries an abnormally long run of the amino acid it codes for. That altered protein damages neurones in the brain, and it does so whether or not a normal huntingtin is also present, which is why the allele is dominant. A single copy is enough, every child of an affected parent has a one in two chance of inheriting it, and the symptoms usually appear between the ages of thirty and fifty, so people often have children before they know. Dominant means only that the allele's effect appears in a heterozygote; it says nothing about how common the allele is.

The last row names the gene behind the standard pea example. The tall and dwarf phenotypes of the crosses above are controlled by the gene Le. The functional allele, Le, codes for an enzyme that carries out the last step in making an active gibberellin, the growth substance that lengthens the internodes of a stem. The allele le codes for a version of that enzyme which does not work, so a plant of genotype le le makes very little active gibberellin, its internodes stay short and it is a dwarf. A heterozygote, Le le, has one working copy, makes enough of the enzyme and grows tall, so tall is dominant for the same reason albinism is recessive.

A testable prediction follows. Supplying active gibberellin to a dwarf pea plant causes it to grow tall, because the plant lacks the product rather than the ability to respond to it. Supplying it to a tall plant has little effect, since the plant already makes sufficient gibberellin. Supplying tyrosine does not restore pigmentation in oculocutaneous albinism type 1, because tyrosine is the substrate of the missing enzyme: only a product beyond the blocked step could bypass it, as gibberellin does for the dwarf pea.