Chapter 9: Gene Mapping and Cancer Genetics
In 1913, a young undergraduate student named Alfred Sturtevant was working in the laboratory of T. H. Morgan at Columbia University, in a crowded room full of glass bottles of fruit flies. Morgan’s team had already noticed something strange: certain traits in Drosophila refused to be inherited independently. They travelled together from parent to offspring far more often than chance allowed — but not always. Every now and then, a fly appeared with a brand-new combination of traits.
Morgan suspected that these genes sat on the same chromosome, and that they were occasionally swapped when chromosomes exchanged pieces during meiosis. The numbers were there in the laboratory notebooks, but nobody knew what to do with them.
Sturtevant did. One evening he took the data home, set his college homework aside, and worked through the night. His idea was simple: if two genes are separated more often, they must be lying further apart on the chromosome. So the percentage of new combinations could be read as a distance. By morning he had drawn the first map of genes on a chromosome — six genes on the X chromosome of the fruit fly, arranged in order, with distances between them.
He had never seen a gene. He had only counted flies.
Diagram
Fig. 9.1 – A pair of homologous chromosomes crossing over during meiosis, with the resulting linear gene map drawn beside it showing genes A, B and C in order with distances marked in map units; label chromatids, chiasma, parental combinations and recombinant combinations
This chapter will help you answer each of these questions.
9.1 Linkage and Linkage Groups
In the previous chapter you learnt Mendel’s law of independent assortment, which states that the alleles of two different traits separate into gametes independently of each other. Mendel’s pea plants obeyed this law beautifully. But as soon as biologists began studying other traits and other organisms, they ran into pairs of characters that simply refused to behave this way.
The reason is straightforward once you remember what a chromosome actually is. A chromosome is not a carrier of one single gene. It is a long thread of DNA along which hundreds or thousands of genes are arranged one after another, like beads strung on a string. Genes that sit on the same chromosome are physically joined to one another. When that chromosome moves into a gamete during meiosis, every gene on it tends to travel along with it.
Genes that lie on the same chromosome and tend to be inherited together are called linked genes, and the tendency itself is called linkage.
Diagram
Fig. 9.2 – Two homologous chromosomes, one carrying alleles A and B and the other carrying a and b, shown passing intact into gametes; label linked genes, chromosome, and the two parental gamete types produced
How Linkage Was Discovered
The first hint came from sweet pea plants, not from Mendel’s garden pea.
The explanation came a few years later. In 1910, T. H. Morgan, working with the fruit fly Drosophila melanogaster, showed clearly that such genes are linked because they are carried on the same chromosome. Since then linkage has been demonstrated in rabbits, poultry, mice, many insects, and in plants such as maize, wheat, sweet peas, tomatoes, primroses and snapdragons.
Characteristics of Linkage
The behaviour of linked genes can be summed up in four points:
- Linkage is an exception to Mendel’s law of independent assortment.
- Genes are arranged linearly on a chromosome, and each linked gene has a definite, fixed order in that arrangement.
- Linked genes tend to be transmitted together from one generation to the next.
- The lesser the distance between two linked genes, the stronger is the linkage between them.
The fourth point is the one that matters most for the rest of this chapter, so it is worth pausing on. Two genes sitting almost side by side on a chromosome are very rarely pulled apart, and so they behave as an almost inseparable pair. Two genes lying at opposite ends of the same chromosome are on the same thread, yet they are separated so often that they may look almost unlinked. Distance, in other words, weakens linkage — and that relationship is exactly what makes gene mapping possible in Section 9.3.
Linkage Groups
All the genes carried on one pair of homologous chromosomes are inherited as one connected set. Such a set is called a linkage group. The concept was introduced by Sutton and later supported by Morgan’s experimental work.
Since every pair of homologous chromosomes forms one linkage group, the number of linkage groups in a species cannot exceed the number of chromosome pairs it possesses. This gives a simple and very useful rule: the number of linkage groups in a species is equal to its haploid number of chromosomes. This upper limit is known as the limitation of linkage groups.
| Species | Diploid number (\(2n\)) | Number of linkage groups |
|---|---|---|
| Maize | \(2n = 20\) | 10 |
| Drosophila | \(2n = 8\) | 4 |
| Pea | \(2n = 14\) | 7 |
| Man | \(2n = 46\) | 23 |
Linkage groups are not all of the same size. A large chromosome carries more genes and therefore forms a big linkage group, while a small chromosome forms a correspondingly small one. Within any one linkage group the degree of linkage between any two members is fairly constant, but it differs from one pair of genes to another, depending on how far apart they lie. Characters belonging to different linkage groups are on different chromosomes, and these obey Mendel’s second law normally.
This “haploid number” relationship is a favourite of one-mark objective and assertion–reason questions, which usually supply the diploid number and expect you to halve it before answering.
9.2 Crossing Over and Genetic Recombination
If linkage were absolute, the genes on a chromosome would be locked together forever and every offspring would be a copy of one parent or the other in those traits. Nature is not that rigid. Linked genes are separated from time to time, and the process that separates them is crossing over.
To follow it clearly, begin at fertilisation. Each gamete carries a haploid set of chromosomes, and the two gametes fuse so that the zygote — and every somatic cell that develops from it — carries a diploid set. The chromosomes therefore exist in pairs, one member of each pair having come from the mother and the other from the father. The two members of such a pair are said to be homologous: they are alike in size, shape and the sequence of gene positions they carry, though the actual alleles at those positions may differ.
Crossing Over During Meiosis
When the individual later forms its own gametes, meiosis takes place. During prophase I of meiosis, the homologous chromosomes come to lie side by side and pair lengthwise. This precise pairing is called synapsis, and the paired structure is a bivalent. By this stage each chromosome has already duplicated, so the bivalent contains four chromatids.
While they are paired, the arms of the chromatids often twist around one another. At the points where they cross, X-shaped junctions become visible under the microscope. These junctions are called chiasmata (singular: chiasma). At a chiasma, two of the four chromatids — one from each homologue, and never two chromatids of the same chromosome — break at exactly corresponding points and rejoin with each other’s partner. The result is that a segment of the maternal chromatid is now attached to the paternal chromatid and vice versa.
Diagram
Fig. 9.3 – A bivalent in prophase I showing four chromatids, with a chiasma formed between two non-sister chromatids; label homologous chromosomes, sister chromatids, non-sister chromatids, chiasma, and the exchanged segments after crossing over
Because the exchange happens between corresponding points, no genetic material is gained or lost. What changes is the combination of alleles carried along each chromatid. Genes that entered meiosis linked together on the maternal chromosome are handed over to the paternal chromosome, and vice versa. When these chromatids separate at anaphase and pass into gametes, each gamete may carry a chromosome that is partly maternal and partly paternal in origin.
Flowchart
FC 9.1 – Crossing over: homologous chromosomes pair by synapsis in prophase I → each chromosome already has two chromatids, giving four chromatids in the bivalent → non-sister chromatids cross and form chiasmata → breakage occurs at corresponding points → the broken segments rejoin with the opposite chromatid → chromatids separate at anaphase → gametes receive chromosomes carrying new combinations of linked genes
Note carefully that it is the chromatids, not the whole chromosomes, that break and rejoin — and that the exchange is always between non-sister chromatids. An exchange between the two sister chromatids of one chromosome would achieve nothing, because sister chromatids are identical copies and swapping identical pieces produces no new combination at all.
In your Paper II practical work you observe permanent slides of meiosis and identify its stages. The chiasmata described here are exactly what makes certain prophase I stages recognisable under the microscope — the bivalents appear held together at X-shaped points even as the homologues begin to move apart.
Genetic Recombination
The outcome of crossing over has its own name.
This gives us two kinds of offspring from a cross involving linked genes. Individuals carrying the same allele combinations that the parents had are called parental types. Individuals carrying new combinations, produced by crossing over, are called recombinant types.
The proportion of recombinant offspring is not a random figure. Crossing over can occur anywhere along the length of the paired chromosomes, so the longer the stretch of chromosome lying between two genes, the greater the chance that a chiasma will form somewhere in between and separate them. Genes lying close together are separated rarely and give few recombinants; genes lying far apart are separated often and give many. This is the quantitative relationship on which the whole of the next section rests. Morgan used precisely this reasoning on his Drosophila data and was eventually able to assign positions to more than 400 genes.
Significance of Crossing Over
Crossing over matters far beyond the genetics laboratory. It is one of the major sources of genetic variation in sexually reproducing organisms, shuffling maternal and paternal alleles into combinations that have never existed before. Variation is the raw material on which natural selection acts, so crossing over contributes directly to the evolutionary flexibility of a population.
Plant and animal breeders depend on it in a very practical way. A desirable disease-resistance gene and an undesirable gene may sit on the same chromosome in a wild variety. Only recombination can break that unwanted association and allow the useful gene to be moved into a cultivated variety without dragging the harmful one along with it. Finally, as you will see next, the measurable frequency of crossing over is the tool that allows genes to be located on chromosomes.
9.3 Gene Mapping and Crossing Over Value
Two genes on the same chromosome are separated only when a chiasma forms in the stretch of chromosome lying between them. That single fact turns a breeding experiment into a measuring instrument. If we count how often two genes are separated, we are indirectly measuring how much chromosome lies between them.
Crossing Over Value
The frequency with which crossing over separates two linked genes is expressed as the crossing over value (COV), also called the recombination frequency. It is calculated from the offspring of a suitable cross by counting how many carry new combinations of the two traits.
\[\text{COV} = \frac{\text{Number of recombinant offspring}}{\text{Total number of offspring}} \times 100\]
Here the number of recombinant offspring is the count of individuals showing allele combinations absent in the parents, and the total is the count of all offspring scored. Both are simple whole numbers of individuals, so COV is a pure percentage with no unit.
Chromosome Maps
Once COV can be measured for several pairs of genes on the same chromosome, the genes can be arranged in order and a map can be drawn.
The map rests on Morgan’s hypothesis, that the frequency of crossing over between two genes is directly proportional to the physical distance separating them on the chromosome. Distance on such a map is therefore measured in units of recombination.
One map unit, also called a centimorgan (cM) in honour of Morgan, is defined as 1% recombination between two genes.
Constructing a Map from Recombination Data
Suppose three genes A, B and C lie on the same chromosome, and crossing over values are measured as 10% between A and B, 15% between B and C, and 25% between A and C.
The largest value tells you which two genes are the outermost pair, because the two genes furthest apart must show the highest recombination. Here A and C are the outer genes, so B must lie between them. The arrangement is confirmed by addition: the distance from A to B plus the distance from B to C is \(10 + 15 = 25\), which is exactly the observed A–C value. The map is therefore:
Diagram
Fig. 9.4 – A horizontal line representing a chromosome with three points marked A, B and C in order; arrows showing 10 map units between A and B, 15 map units between B and C, and the total 25 map units spanning A to C
- Count the parental and recombinant individuals for each pair of genes.
- Calculate the crossing over value for each pair using the COV formula.
- Convert each percentage into map units (1% = 1 cM).
- Identify the outermost pair from the largest value and place the remaining gene between them; check that the two shorter distances add up to the longest.
- Draw the genes in order on a straight line with the distances marked. Used for: Locating genes on chromosomes and fixing their order and spacing; used in plant and animal breeding to follow desirable genes, and historically the basis of the first maps of human chromosomes.
Limitations of Gene Maps
Maps built this way are extremely useful, but they are estimates rather than exact physical measurements. Four limitations should be remembered:
- They are not very accurate, because map distance is inferred from recombination behaviour rather than measured directly along the DNA.
- Heterochromatin decreases recombination frequency, so regions rich in it appear shorter on the map than they really are.
- One crossover reduces the frequency of another crossover occurring nearby, so recombinants are undercounted over longer stretches.
- Recombination frequency increases towards the ends of chromosomes, so equal map distances in different regions do not represent equal lengths of DNA.
The third and fourth points explain a puzzle students often meet in numerical problems: over long distances, the observed COV between the two outermost genes turns out to be less than the sum of the shorter distances. A second crossover between the same two genes restores the original parental combination, and such double crossovers are scored as parental types even though two exchanges have taken place. The longer the interval, the more such events are missed, and the more the map underestimates the true distance.
Significance of Chromosome Maps
- Chromosome maps confirm that genes occur in a linear order along the chromosomes.
- They show that genes occupy fixed points, or loci, on chromosomes.
- They help in locating particular genes on specific chromosomes.
- They allow the results of a dihybrid or trihybrid cross to be predicted in advance.
- They predict the chances of recombination, which allows breeding programmes to be planned and manipulated intelligently.
Gene-order construction from a set of recombination values is one of the most commonly set application questions on this topic, and the marks usually lie in justifying the order — showing that the two shorter distances add up to the longest — rather than in drawing the line itself.
9.4 Cancer and Its Causes
So far this chapter has treated genes as markers to be counted and mapped. Now we turn to what happens when particular genes — the ones that govern cell division itself — are damaged.
In a healthy body, cells divide in a controlled and organised manner. After dividing, they undergo differentiation and take up specialised functions: a liver cell does liver work, a skin cell replaces worn-out skin. As you learnt while studying the cell cycle, this whole schedule is regulated by proteins called cyclins, which act together with enzymes known as cyclin dependent kinases (CdK). Cyclin–CdK pairs act as the switches that allow the cycle to move from one phase to the next.
When the Control System Fails
The cycle is monitored at checkpoints, and two of them matter especially here: the checkpoint between the G1 and S phases and the one between the G2 and M phases. At each checkpoint the cell is, in effect, asked whether conditions are fit to proceed — is the DNA undamaged, has replication been completed correctly, are growth signals present?
Diagram
Fig. 9.5 – The cell cycle drawn as a circle with G1, S, G2 and M phases marked; label the G1–S checkpoint and the G2–M checkpoint, and show cyclin–CdK complexes acting as the switches that permit progression
When these checkpoints fail, a cell with damaged DNA or without proper signals is allowed through anyway. It divides again, and its daughters inherit the same fault and the same lack of control. Division continues without proper differentiation, and the growing mass of undifferentiated, uncontrolled cells forms a tumour, also called a neoplasm.
A tumour causes harm in mechanical as well as biochemical ways. As it enlarges it compresses the surrounding tissues, blocks the flow of blood, and interferes with nerve signals, eventually damaging or killing normal cells around it.
The most dangerous step comes when cancer cells detach from their original site and travel through the blood or the lymph to other parts of the body, where they settle and establish secondary tumours. This spread is called metastasis.
Carcinogenesis
Cancer does not appear overnight. It develops gradually, usually over years, through the accumulation of several changes in the same cell line, and it is often the result of internal and external factors acting together. Substances capable of causing cancer are called carcinogens, and the whole process by which a normal cell becomes cancerous is called carcinogenesis.
Flowchart
FC 9.2 – Carcinogenesis: normal regulated cell → exposure to a carcinogen or spontaneous mutation → mutation in genes controlling cell division → failure at the G1–S or G2–M checkpoint → uncontrolled division without differentiation → tumour formation → invasion of surrounding tissue → detachment of cells into blood or lymph → secondary tumours (metastasis)
The most widely accepted cause of cancer is mutation in the genes that regulate cell division. Such mutations may arise from exposure to something in the environment, or simply from the accumulating chance of error as cells go on dividing over a long lifetime. This is why the risk of cancer rises with age.
Physical, Chemical and Biological Causes
The many factors that contribute to cancer are conveniently grouped under three headings.
Physical carcinogens are forms of energy that damage DNA directly. These include exposure to radiation such as X-rays, ultraviolet rays and radioactive substances. Ultraviolet radiation in sunlight is the reason repeated, unprotected sun exposure is linked to skin cancer, and it is also why radiographers stand behind a shielded screen while an X-ray is taken.
Chemical carcinogens are substances that react with DNA or alter the way it is copied. Well-known examples include asbestos, once widely used in roofing and insulation, and benzene, an industrial solvent.
Biological causes include viral infections and inherited genetic susceptibility. Certain viruses can disturb the genes that control division in the cells they infect, and some families carry inherited faults in these genes that make cancer more likely from birth. Because these biological causes act directly on the genes controlling cell division, they are dealt with in detail in the next section, along with the two classes of genes involved.
9.5 Oncogenes and Tumour Suppressor Genes
The previous section ended with a general statement: cancer arises from mutations in the genes that regulate cell division. Those genes fall into two contrasting groups, and it helps to think of them the way you would think of the controls of a vehicle. One group works like the accelerator, urging division forward. The other works like the brakes, holding division back until it is genuinely needed. A vehicle runs out of control either because the accelerator jams down or because the brakes fail — and cancer arises in exactly these two ways.
Diagram
Fig. 9.6 – A vehicle-control analogy for cancer genes: a normal cell shown with a working accelerator (proto-oncogene) and working brakes (tumour suppressor gene), beside a cancerous cell with a jammed accelerator (oncogene) and failed brakes (inactivated TSG); label gain of function and loss of function
Proto-oncogenes
Proto-oncogenes are perfectly normal genes present in every healthy cell. They play an important part in promoting cell growth and division, providing the positive signals that permit a cell to divide when the body needs new cells — during growth, during wound healing, or during the routine replacement of worn-out tissue. In some cases they also regulate the orderly death of cells that are no longer required.
A proto-oncogene is therefore not a harmful gene. It becomes harmful only when it mutates. A mutation may leave the gene permanently switched on, or produce far too much of its product, so that the signal to divide is given continuously instead of only when required. Such an overactive, mutated proto-oncogene is called an oncogene.
Flowchart
FC 9.3 – From proto-oncogene to cancer: normal proto-oncogene gives measured signals for division → mutation caused by radiation, chemicals or viral interference → gene becomes overactive (gain of function) → oncogene now signals continuously → cell divides without differentiation → tumour formation
How Oncogenes Were Discovered
Oncogenes were first discovered not in human patients but in tumour-causing viruses, especially the RNA viruses known as retroviruses.
The story was completed much later by Harold Varmus and J. Michael Bishop, who demonstrated that genes very similar to the cancer-causing genes of these viruses are already present in normal cells. The versions found in normal cells are called cellular oncogenes (c-onc genes), while the versions carried by the viruses are called viral oncogenes (v-onc genes). In other words, the virus had not invented the cancer gene — it had picked up a copy of one of ours.
There is a neat piece of evidence for this. A v-onc gene is derived from processed mRNA, and since the non-coding stretches have already been removed from mRNA, v-onc genes lack introns. The corresponding c-onc genes in cellular DNA contain both exons and introns, as ordinary cellular genes do.
Cancer-causing DNA Viruses
Certain DNA viruses also contribute to cancer, by integrating their genetic material into the DNA of the host cell. The SV40 virus, for example, can insert part of its genome into host DNA and thereby transform the cell.
Such viruses may infect cells in two contrasting ways.
Papillomaviruses, which contain double-stranded circular DNA, illustrate the same principle. Inside host cells they usually remain harmless, existing separately from the host chromosome much as plasmids do in bacteria. If genetic changes cause their DNA to become integrated into a host chromosome, however, they disrupt the normal regulation of cell division and may lead to cancer.
Tumour Suppressor Genes
The second group of genes works in the opposite direction. Tumour suppressor genes (TSG) act to control and restrain cell division. Their products inhibit division until division is genuinely required, ensuring that cells divide only when necessary and that division stops when DNA is damaged or when growth signals are absent. Well-studied examples include the p53 and RB genes.
The conditions under which these genes act as a brake are exactly the conditions that should stop a cell in its tracks: DNA damage, a lack of growth factors, or a defect in the cell division machinery itself. Cancer develops when these genes lose their function and the brake is no longer applied.
This is the crucial contrast with oncogenes. It is the loss of function of a tumour suppressor gene that leads to trouble, whereas an oncogene in its mutant form has gained a function — or, more precisely, has lost the ability to be controlled.
Notice that cancer usually needs both things to go wrong somewhere along the way — a jammed accelerator and failed brakes — which is another reason carcinogenesis is gradual rather than sudden. It also explains why a person may inherit a faulty copy of a tumour suppressor gene and remain healthy for years, yet carry a higher lifetime risk: they begin life already one step along the path, needing fewer further mutations than someone born with two intact copies.
9.6 Diagnosis and Treatment of Cancer
Knowing how cancer arises is only useful if it can be found and dealt with in a patient. Both the finding and the dealing follow from what you have just learnt: cancer cells divide when they should not, they look and behave unlike the tissue they came from, and they may already have travelled elsewhere in the body.
Diagnosis of Cancer
Cancer diagnosis is a step-by-step process used to detect and confirm the presence of abnormal or cancerous cells in the body. No single test does everything. Each step narrows the possibilities, and the last step provides certainty.
Physical examination
Diagnosis usually begins with a physical examination, in which the doctor checks for unusual lumps or swellings and asks about general symptoms such as unexplained weight loss and persistent fatigue. These signs are not proof of anything by themselves — many harmless conditions produce them — but they tell the doctor where to look and what to test for next.
Imaging techniques
The next step is to see inside the body without opening it. Imaging techniques such as X-rays, CT scans, MRI and PET scans help in locating a tumour and in understanding its size and how far it has spread. Imaging is particularly valuable for answering the question that decides treatment: is the growth confined to one place, or has it metastasised?
Laboratory tests
Laboratory tests, especially blood tests, are also performed. Some tumours release characteristic substances into the blood, called tumour markers, and an unusually high level of such a marker can point towards cancer. Blood tests also reveal abnormalities in the blood cells themselves, which matters greatly in cancers of the blood and bone marrow. The blood smear you prepare and stain with Leishmann’s stain in your Paper II practical work is the same basic preparation a pathologist examines — the difference lies only in what is being looked for in the field of view.
Biopsy
The most important and confirmatory step in diagnosis is a biopsy, in which a small sample of tissue is taken from the suspected area and examined under a microscope.
Diagram
Fig. 9.7 – Side-by-side microscopic views of a stained tissue section: normal tissue with regularly arranged, uniform cells, and cancerous tissue with irregular, crowded cells having enlarged nuclei and several cells in mitosis; label normal tissue and cancerous tissue
Endoscopy
In some cases endoscopy is used, in which a flexible tube fitted with a camera is passed into the body so that internal organs can be observed directly. Endoscopy has a double advantage: the doctor can see a suspicious area with their own eyes, and can usually take a biopsy sample from it during the same procedure.
Flowchart
FC 9.4 – Diagnosis of cancer: physical examination for lumps, swelling and general symptoms → imaging (X-ray, CT, MRI, PET) to locate the tumour and assess its spread → laboratory and blood tests for tumour markers → endoscopy for direct visual examination where applicable → biopsy and microscopic examination for confirmation
Treatment of Cancer
Cancer treatment depends on the type, stage and location of the disease, and it very often involves a combination of different methods rather than any single one.
Surgery is used to remove the tumour, and is especially effective in the early stages when the growth is still localised. Its logic is direct: if all the cancerous tissue can be taken out, the disease is gone.
Radiation therapy uses high-energy rays to destroy cancer cells in a targeted area. The rays damage DNA so severely that the cell cannot complete division, and rapidly dividing cells are the most vulnerable — which is precisely why cancer cells suffer more than the surrounding tissue.
Chemotherapy involves the use of drugs that kill rapidly dividing cells. Because the drugs travel through the bloodstream, chemotherapy can reach cancer cells that surgery and radiation cannot, including cells that have already spread. Its weakness follows from the same principle: it cannot tell one rapidly dividing cell from another, so it also affects normal cells that divide quickly.
Immunotherapy helps the body’s own immune system to fight cancer more effectively. Cancer cells arise from the body’s own tissues and are often not recognised as a threat; immunotherapy works by making them visible to the immune system or by strengthening the immune response against them.
Hormone therapy is used in certain cancers, such as breast and prostate cancer, to block the hormones that promote tumour growth. It is effective only where the tumour actually depends on a hormone for its growth — which is why the type of cancer must be established by biopsy before this route is chosen.
Targeted therapy focuses on specific molecules involved in cancer development, such as the abnormal products of oncogenes. Because it acts on a molecule that is largely peculiar to the cancer cells rather than on cell division in general, it is more precise and causes fewer side effects.
Early diagnosis and a properly chosen combination of these treatments greatly improve the chances of recovery. That single sentence brings the two halves of this chapter together: the treatments now aimed at specific molecules exist only because the genes controlling cell division were first located, studied and understood.
9.7 Summary
A chromosome carries many genes arranged linearly along its length. Genes lying on the same chromosome tend to be inherited together and are called linked genes; the tendency itself is called linkage.
Linkage is an exception to Mendel’s law of independent assortment, which applies only to genes on different chromosomes.
Linkage was first noticed by Bateson and Punnett in 1906 in sweet pea, where purple flowers and long pollen kept appearing together; they called it the coupling of factors. T. H. Morgan explained it clearly in 1910 using Drosophila, showing that such genes lie on the same chromosome.
The main characteristics of linkage are: it is an exception to independent assortment; genes have a definite linear order; linked genes are transmitted together; and the shorter the distance between two genes, the stronger their linkage.
All the genes on one pair of homologous chromosomes form a linkage group. The concept was introduced by Sutton. The number of linkage groups in a species equals its haploid number of chromosomes — 10 in maize (\(2n = 20\)), 4 in Drosophila (\(2n = 8\)), 7 in pea (\(2n = 14\)) and 23 in man (\(2n = 46\)).
During prophase I of meiosis, homologous chromosomes pair by synapsis. Non-sister chromatids cross at points called chiasmata, break at corresponding positions and rejoin with each other, exchanging equal segments. This exchange is crossing over.
Crossing over produces new combinations of linked alleles. Offspring carrying the parental combinations are parental types; those carrying new combinations are recombinant types, and their production is called genetic recombination.
Crossing over is a major source of genetic variation, supplies the variation on which natural selection acts, allows breeders to separate a desirable gene from an undesirable one on the same chromosome, and makes gene mapping possible.
The crossing over value (COV) is the percentage of recombinant offspring in a cross: \[\text{COV} = \frac{\text{Number of recombinant offspring}}{\text{Total number of offspring}} \times 100\] A low COV means the genes are close together and strongly linked; a high COV means they are far apart and weakly linked.
A chromosome map is a linear representation of the order and relative distances of genes on a chromosome. It rests on Morgan’s hypothesis that the frequency of crossing over is directly proportional to the distance between two genes. One map unit, or one centimorgan (cM), equals 1% recombination.
To construct a map from COV data, the largest value identifies the two outermost genes, the remaining gene is placed between them, and the two shorter distances should add up to the largest.
Gene maps are approximate: they are not exact physical measurements, heterochromatin lowers recombination frequency, one crossover reduces the chance of another nearby, and recombination frequency increases towards the chromosome ends.
Despite these limits, chromosome maps confirm the linear arrangement of genes, establish that genes occupy fixed loci, help locate genes on specific chromosomes, allow the results of dihybrid and trihybrid crosses to be predicted, and make breeding programmes plannable.
In normal cells, division is regulated by cyclins acting with cyclin dependent kinases (CdK), and is checked at the G1–S and G2–M checkpoints. Failure at these checkpoints allows division to continue without differentiation, producing a tumour or neoplasm.
Tumours harm the body by compressing tissues, blocking blood flow and interfering with nerve signals. When cancer cells detach and travel through blood or lymph to form secondary tumours elsewhere, the process is called metastasis.
Substances that cause cancer are carcinogens, and the gradual process of cancer formation is carcinogenesis. The most widely accepted cause of cancer is mutation in the genes regulating cell division, arising from environmental exposure or accumulating with age.
Causes of cancer are grouped as physical (X-rays, ultraviolet rays, radioactive substances), chemical (asbestos, benzene) and biological (viral infections, inherited genetic susceptibility).
Proto-oncogenes are normal genes that promote cell growth and division and in some cases regulate cell death. On mutation they become overactive and are then called oncogenes, which can transform normal cells into cancerous ones.
Oncogenes were first discovered in tumour-causing viruses, especially retroviruses. Peyton Rous discovered the Rous Sarcoma Virus (RSV) in 1911. Harold Varmus and J. Michael Bishop later showed that similar genes exist in normal cells: these are cellular oncogenes (c-onc), while the viral versions are viral oncogenes (v-onc). Being derived from mRNA, v-onc genes lack introns, whereas c-onc genes contain both exons and introns.
Certain DNA viruses cause cancer by integrating their genetic material into host DNA; SV40 is one example. In permissive cells the virus multiplies and kills the cell, while in non-permissive cells the viral DNA joins the host genome and leads to abnormal growth. Papillomaviruses, which have double-stranded circular DNA, usually remain harmless outside the host chromosome but may cause cancer if their DNA becomes integrated.
Tumour suppressor genes (TSG) restrain cell division, halting the cycle when DNA is damaged or growth factors are absent. Cancer arises from the loss of function of these genes — in contrast to oncogenes, whose mutant forms have gained function or lost the ability to be controlled.
Diagnosis of cancer proceeds stepwise: physical examination, imaging (X-ray, CT, MRI, PET), laboratory and blood tests for tumour markers, endoscopy where applicable, and finally biopsy, which is the most important confirmatory step because it allows the cells themselves to be examined microscopically.
Treatment depends on the type, stage and location of the cancer and usually combines several methods: surgery for localised tumours, radiation therapy, chemotherapy against rapidly dividing cells, immunotherapy, hormone therapy in cancers such as breast and prostate cancer, and targeted therapy directed at specific molecules involved in cancer development.
Early diagnosis together with a properly chosen combination of treatments greatly improves the chances of recovery.
Flowchart
FC 9.5 – The chapter at a glance: genes arranged linearly on a chromosome → genes on the same chromosome are linked → crossing over at chiasmata in prophase I separates linked genes → recombinant offspring counted → COV calculated → distance in map units → chromosome map constructed; and in parallel: normal cell cycle controlled by cyclin–CdK at checkpoints → mutation in proto-oncogenes (gain of function) or tumour suppressor genes (loss of function) → checkpoint failure → uncontrolled division → tumour → metastasis → diagnosis by examination, imaging, blood tests and biopsy → treatment by surgery, radiation, chemotherapy, immunotherapy, hormone therapy or targeted therapy
9.8 Key Terms
Linked genes genes located on the same chromosome that tend to be inherited together.
Linkage the tendency of two or more genes on the same chromosome to remain together during inheritance.
Coupling of factors the term used by Bateson and Punnett for the tendency of certain characters to appear together in offspring, later explained as linkage.
Linkage group the complete set of linked genes present on one pair of homologous chromosomes.
Limitation of linkage groups the rule that the number of linkage groups in a species equals its haploid number of chromosomes.
Homologous chromosomes the two members of a chromosome pair, one maternal and one paternal, alike in size, shape and the order of gene positions they carry.
Synapsis the lengthwise pairing of homologous chromosomes during prophase I of meiosis.
Bivalent the paired structure formed by two homologous chromosomes at synapsis, containing four chromatids.
Non-sister chromatids chromatids belonging to the two different homologous chromosomes of a bivalent, between which crossing over occurs.
Chiasma the X-shaped junction visible where two non-sister chromatids cross and exchange segments during prophase I.
Crossing over the mutual exchange of corresponding segments between non-sister chromatids of homologous chromosomes during prophase I of meiosis.
Genetic recombination the formation of new combinations of alleles in the offspring that were not present together in either parent.
Parental types offspring carrying the same allele combinations as their parents, produced from chromatids in which no crossing over occurred between the genes concerned.
Recombinant types offspring carrying new allele combinations produced by crossing over.
Crossing over value (COV) the percentage of recombinant offspring in a cross, used as a measure of the distance between two linked genes.
Chromosome map (gene map) a linear diagram showing the order of genes on a chromosome and their relative distances from one another.
Morgan’s hypothesis the principle that the frequency of crossing over between two genes is directly proportional to the physical distance between them.
Map unit (centimorgan, cM) the distance between two genes that shows 1% recombination.
Double crossing over the occurrence of two crossovers between the same pair of genes, which restores the parental arrangement and causes map distance to be underestimated.
Cyclins proteins that regulate progression of the cell through the phases of the cell cycle.
Cyclin dependent kinase (CdK) an enzyme that works together with cyclins to drive the cell cycle from one phase to the next.
Checkpoint a control point in the cell cycle, notably between G1 and S and between G2 and M, at which the cell verifies that conditions are fit for division to proceed.
Tumour (neoplasm) an abnormal mass of cells formed by uncontrolled cell division without proper differentiation.
Benign tumour a tumour that remains confined to its site of origin and does not spread to other parts of the body.
Malignant tumour a tumour that invades surrounding tissue and can spread to distant organs; it is what is called cancer.
Metastasis the spread of cancer cells from their original site through blood or lymph to form secondary tumours elsewhere.
Carcinogen any physical, chemical or biological agent capable of causing cancer.
Carcinogenesis the gradual, multi-step process by which a normal cell is converted into a cancerous cell.
Proto-oncogene a normal cellular gene that promotes cell growth and division and in some cases regulates cell death.
Oncogene a mutated, overactive form of a proto-oncogene that drives uncontrolled cell division and can transform a normal cell into a cancerous one.
Retrovirus an RNA virus of the group in which cancer-causing genes were first discovered.
Rous Sarcoma Virus (RSV) the tumour-inducing virus discovered by Peyton Rous in 1911 in chickens.
Cellular oncogene (c-onc) the version of an oncogene present in normal cells, containing both exons and introns.
Viral oncogene (v-onc) the version of an oncogene carried by a virus, derived from mRNA and therefore lacking introns.
SV40 virus a DNA virus that can insert part of its genome into host DNA and thereby transform the cell.
Permissive cells cells in which an infecting virus multiplies freely and eventually causes cell death.
Non-permissive cells cells in which the viral DNA becomes part of the host genome, leading to abnormal cell growth instead of cell death.
Papillomaviruses viruses containing double-stranded circular DNA that usually remain harmless outside the host chromosome but may cause cancer if their DNA becomes integrated into it.
Tumour suppressor gene (TSG) a gene whose product inhibits cell division until it is required, and whose loss of function leads to cancer.
Tumour marker a substance released by certain tumours whose raised level in the blood may indicate the presence of cancer.
Biopsy the removal of a small tissue sample from a suspected site for microscopic examination; the most confirmatory step in cancer diagnosis.
Endoscopy examination of internal organs using a flexible tube fitted with a camera, which also allows tissue samples to be taken.
Radiation therapy treatment that uses high-energy rays to destroy cancer cells in a targeted area.
Chemotherapy treatment using drugs that kill rapidly dividing cells, including some normal cells.
Immunotherapy treatment that helps the body’s own immune system to recognise and fight cancer cells more effectively.
Hormone therapy treatment used in cancers such as breast and prostate cancer to block the hormones that promote tumour growth.
Targeted therapy treatment directed at specific molecules involved in cancer development, giving greater precision and fewer side effects.
9.9 Points to Ponder
Linkage keeps useful combinations of genes together, while crossing over breaks them apart. Both are widespread in nature. Why might a species benefit from having some of both rather than one or the other?
Sturtevant built the first gene map without ever seeing a gene, using nothing but counts of offspring. What does this tell you about the relationship between measurement and direct observation in science?
A gene map gives the order of genes correctly but not their true physical distances in DNA. Is a map that is accurate in order but inaccurate in scale still a scientific map? What is it good for, and what should it never be used for?
Male Drosophila show no crossing over at all. Imagine a species in which this were true of both sexes. How would its genetics, and its capacity to adapt to a changing environment, differ from ours?
Modern genome sequencing can locate a gene to the exact base pair. Does this make classical linkage mapping obsolete, or does recombination data still tell us something that a sequence cannot?
Cancer is often described as a disease of our own genes rather than an invasion from outside. What does this description change about how we think of prevention, of blame, and of the patient?
Some carcinogens, such as asbestos, produce disease only decades after exposure. What difficulties does such a long delay create for proving harm, for regulating an industry, and for compensating those affected?
A person may inherit a faulty copy of a tumour suppressor gene and remain perfectly healthy for many years. If such a fault can now be detected by a genetic test, who should be entitled to know the result — the person, their relatives who may share the same fault, an employer, an insurer? Consider what each party stands to gain and to lose.
Chemotherapy works by attacking rapidly dividing cells, which is why it damages healthy tissue as well. Is a treatment that harms the patient in order to help them ethically different from one that does not, or is the distinction only a matter of degree?
Targeted therapies are more precise but far more expensive than older treatments, and they depend on identifying the specific molecular target in each tumour. What does this imply about who is likely to benefit from advances in cancer treatment first, and what could be done about it?
Cancer screening can find tumours early, but it can also detect growths that would never have caused harm in a person’s lifetime, leading to treatment that was never needed. How would you weigh the benefit of early detection against the cost of over-treatment?
Peyton Rous’s conclusion that a virus could cause cancer was largely ignored for decades before it was accepted. What does the history of this idea suggest about how scientific communities respond to evidence that does not fit the thinking of their time?
9.10 Objective Questions
- An organism has a diploid chromosome number of \(2n = 24\). How many linkage groups does it possess?
- 6
- 12
- 24
- 48
- The exchange of segments during crossing over takes place between:
- Sister chromatids of the same chromosome
- Non-sister chromatids of homologous chromosomes
- Chromatids of non-homologous chromosomes
- Two entire homologous chromosomes
- The X-shaped junction seen where two chromatids cross during prophase I is called:
- Centromere
- Chiasma
- Bivalent
- Telomere
- In a cross, 900 offspring were scored, of which 810 were of parental type. What is the crossing over value between the two genes?
- \(9\%\)
- \(10\%\)
- \(81\%\)
- \(90\%\)
- The concept of linkage groups was introduced by:
- Mendel
- Sutton
- Bateson
- Bishop
- Bateson and Punnett described the tendency of purple flowers and long pollen to appear together in sweet pea as:
- Coupling of factors
- Independent assortment
- Synapsis
- Segregation
- Three genes give the following crossing over values: L–M = 6%, M–N = 9%, L–N = 15%. The correct order of the genes on the chromosome is:
- M – L – N
- L – M – N
- L – N – M
- N – M – L
- Which of the following would cause the measured map distance between two distant genes to be smaller than the true distance?
- Single crossing over
- Double crossing over
- Synapsis
- Independent assortment
- Recombination frequency is reduced in regions of a chromosome that are rich in:
- Euchromatin
- Heterochromatin
- Telomeres
- Ribosomes
- The cell cycle is driven from one phase to the next by cyclins acting together with:
- Ligases
- Cyclin dependent kinases
- Topoisomerases
- Restriction enzymes
- Which pair of checkpoints is most directly associated with the loss of cell cycle control in cancer?
- G1–S and G2–M
- S–G2 and M–G1
- G0–G1 and S–M
- G2–S and M–G2
- Asbestos and benzene are examples of:
- Physical carcinogens
- Chemical carcinogens
- Biological carcinogens
- Tumour markers
- The virus discovered by Peyton Rous in 1911 belongs to which group?
- Double-stranded DNA viruses
- Retroviruses
- Bacteriophages
- Plant viruses
- A v-onc gene lacks introns because it is derived from:
- Genomic DNA of the host
- Processed mRNA
- Ribosomal RNA
- A plasmid
- In non-permissive cells, an infecting DNA virus most commonly leads to:
- Rapid multiplication of the virus and cell death
- Integration of viral DNA and abnormal cell growth
- Immediate destruction of the viral genome
- Normal differentiation of the cell
- Cancer arising from a tumour suppressor gene is associated with:
- Gain of function
- Loss of function
- Gene duplication
- Increased transcription of the gene
- A raised level of a particular substance in a patient’s blood suggests, but does not confirm, the presence of a tumour. Such a substance is called a:
- Carcinogen
- Tumour marker
- Cyclin
- Mutagen
- Hair loss and a fall in blood cell counts during chemotherapy occur because the drugs act on:
- Only cancer cells
- All rapidly dividing cells
- Non-dividing cells only
- Cells of the nervous system
- Hormone therapy is a suitable treatment mainly for cancers of the:
- Skin and bone
- Breast and prostate
- Brain and spinal cord
- Liver and kidney
- Targeted therapy causes fewer side effects than chemotherapy because it acts on:
- All dividing cells at a lower dose
- Specific molecules involved in cancer development
- The immune system alone
- Hormone receptors in every tissue
- For the following questions, choose the correct option from the set given below:
- Both Assertion and Reason are true, and Reason is the correct explanation of Assertion.
- Both Assertion and Reason are true, but Reason is not the correct explanation of Assertion.
- Assertion is true, but Reason is false.
- Both Assertion and Reason are false.
- Assertion (A): The number of linkage groups in an organism equals its haploid chromosome number. Reason (R): All the genes carried on one pair of homologous chromosomes are inherited as a single connected set.
- Assertion (A): Crossing over between sister chromatids would not produce recombinant offspring. Reason (R): Sister chromatids are identical copies, so exchanging segments between them produces no new allele combination.
- Assertion (A): The crossing over value between two genes can never exceed 50%. Reason (R): Only two of the four chromatids of a bivalent take part in any single exchange.
- Assertion (A): A chromosome map gives the correct order of genes but not their true physical distances. Reason (R): Map distance is inferred from recombination behaviour rather than measured along the DNA.
- Assertion (A): In a three-gene mapping problem, the largest crossing over value identifies the two outermost genes. Reason (R): The two genes farthest apart on a chromosome are separated by crossing over most often.
- Assertion (A): Proto-oncogenes are harmful genes that must be removed from normal cells. Reason (R): They provide the positive signals that allow cells to divide during growth and wound healing.
- Assertion (A): A single mutated copy of a proto-oncogene is usually enough to promote uncontrolled division. Reason (R): The overactive copy continues to signal for division and the normal copy cannot silence it.
- Assertion (A): Papillomaviruses are dangerous only when their DNA becomes integrated into a host chromosome. Reason (R): While the viral DNA remains separate from the host chromosome, it does not interfere with the genes controlling cell division.
- Assertion (A): Imaging techniques such as CT and MRI can confirm the diagnosis of cancer. Reason (R): Imaging reveals the size and location of a mass but not the nature of the cells composing it.
- In a genetic study, two traits are always inherited together across generations. It is concluded that the genes controlling these traits are located on the same chromosome. What are such genes called?
- Alleles
- Linked genes
- Dominant genes
- Mutant genes
- A genetic map shows distances between genes expressed numerically on the basis of recombination frequency. What unit is being used here?
- Base pair
- Dalton
- Centimorgan
- Codon
- During microscopic observation of meiosis, homologous chromosomes are seen exchanging segments at an early stage. During which phase does this process occur?
- Prophase-I
- Metaphase-II
- Anaphase-I
- Telophase-II
- A gene normally regulates cell growth, but after mutation it begins to promote uncontrolled cell division. What is the mutated form of this gene called?
- Structural gene
- Oncogene
- Tumour suppressor gene
- Regulatory gene
- Certain chemicals like benzene are known to induce cancer in organisms. Such substances are classified as:
- Antigens
- Mutagens
- Carcinogens
- Enzymes
- Two genes located far apart on the same chromosome are frequently separated during meiosis and inherited independently. What explains this observation?
- Mutation frequency is high
- Crossing over occurs frequently between them
- They belong to different chromosomes
- One gene is recessive
- Some traits do not follow Mendel’s law of independent assortment and tend to be inherited together. Which concept explains this exception?
- Dominance
- Segregation
- Linkage
- Mutation
- New combinations of traits appear in offspring that were not present in the parents. Which process is primarily responsible for this?
- Fertilization
- Replication
- Crossing over
- Mutation
- Certain genes ensure that a cell stops dividing when DNA damage is detected. What is the role of such genes?
- Promote division
- Inhibit division when required
- Cause mutation
- Destroy proteins
- Viral DNA integrates into the host genome and leads to abnormal growth of the cell. What is the likely consequence?
- Cell death
- Normal metabolism
- Uncontrolled cell division
- Immediate immunity
- Two traits show only 2% recombination frequency in a genetic cross. What does this suggest about the genes?
- They are unlinked
- They are strongly linked
- They are on different chromosomes
- They are mutated
- As the distance between two genes increases, recombination frequency also increases. What conclusion can be drawn?
- Gene distance decreases
- Gene distance increases
- Mutation rate decreases
- Linkage becomes stronger
- A mutation causes a growth-regulating gene to signal continuously for cell division. What has this gene become?
- Proto-oncogene
- Oncogene
- Suppressor gene
- Allele
- Failure of cell cycle checkpoints results in abnormal cell growth. What is the most likely outcome?
- Controlled division
- Lack of differentiation
- Tumour formation
- Increased apoptosis
- A gene map shows a distance of 10 cM between two genes. What does this indicate?
- 10% recombination
- 1% recombination
- 100% recombination
- No recombination
- In a dihybrid cross, most offspring resemble parental types while very few show recombination. What does this indicate?
- Independent assortment
- Strong linkage
- Mutation
- Random segregation
- Loss of function in tumour suppressor genes leads to:
- Cell cycle arrest
- Controlled division
- Unregulated cell division
- Cell differentiation
- Exchange of genetic material between homologous chromosomes results in new combinations. Which mechanism explains this?
- Replication
- Crossing over
- Segregation
- Mutation
- A very low recombination frequency is observed between two genes. What inference can be made?
- Genes are far apart
- Genes are strongly linked
- Genes are on different chromosomes
- Genes are mutated
- Cancer detection involves imaging and blood tests, but confirmation is done using a tissue sample examined under a microscope. Which method provides confirmation?
- Blood test
- Imaging
- Biopsy
- Physical examination
- Gene mapping is based on recombination frequency, not on exact physical distance. Why is it considered approximate?
- Genes cannot be mapped
- It does not reflect exact physical distance
- Chromosomes are invisible
- Genes do not recombine
- Two processes are compared: one maintains parental combinations, while the other generates variation. Which process contributes more to variation?
- Linkage
- Crossing over
- Segregation
- Replication
- Cancer risk increases due to both environmental exposure and genetic mutations over time. What conclusion best explains this?
- Only environment causes cancer
- Only genetics causes cancer
- Both genetic and environmental factors contribute
- Cancer is random
- A mutated gene derived from a normal growth-regulating gene now promotes cancer. What type of gene is this?
- Tumour suppressor gene
- Oncogene
- Structural gene
- Regulatory gene
- A gene map is constructed using recombination data from genetic crosses. Which principle is applied?
- Mutation rate
- Recombination frequency proportional to gene distance
- DNA replication
- Protein synthesis
- A classroom model uses coloured threads to demonstrate exchange of chromosome segments. What concept is being illustrated?
- Mutation
- Crossing over
- Replication
- Segregation
- A model shows cancer cells spreading from one organ to another through blood circulation. Which process is represented?
- Mutation
- Metastasis
- Differentiation
- Apoptosis
- A project explains cancer development by including both gene mutations and exposure to harmful chemicals. What concept is being highlighted?
- Only genetics
- Only environment
- Interaction of genetic and environmental factors
- Cell division only
- In a gene mapping experiment, parental and recombinant offspring are counted. Why is this important?
- To study mutation
- To calculate recombination frequency
- To observe mitosis
- To measure DNA
- For the following questions, choose the correct option from the set given below:
- Both Assertion and Reason are true, and Reason is the correct explanation of Assertion.
- Both Assertion and Reason are true, but Reason is not the correct explanation of Assertion.
- Assertion is true, but Reason is false.
- Both Assertion and Reason are false.
- Assertion (A): Genes located on the same chromosome are called linked genes. Reason (R): Linked genes always assort independently during inheritance.
- Assertion (A): Crossing over occurs during prophase-I of meiosis. Reason (R): It involves exchange of genetic material between homologous chromosomes.
- Assertion (A): One centimorgan represents 1% recombination frequency. Reason (R): It is used as a unit to measure gene distance on chromosomes.
- Assertion (A): Proto-oncogenes are normal genes involved in cell growth. Reason (R): They suppress uncontrolled cell division under all conditions.
- Assertion (A): Genes located far apart on the same chromosome show weaker linkage. Reason (R): Crossing over is more likely to occur between them.
- Assertion (A): Linkage is considered an exception to Mendel’s law of independent assortment. Reason (R): Linked genes tend to be inherited together instead of assorting independently.
- Assertion (A): Crossing over leads to new gene combinations in offspring. Reason (R): It results in exchange of segments between homologous chromosomes.
- Assertion (A): Tumour suppressor genes regulate cell division. Reason (R): They promote uncontrolled cell growth when active.
- Assertion (A): A recombination frequency of 2% indicates strong linkage between genes. Reason (R): Lower recombination frequency suggests genes are closer together.
- Assertion (A): Mutation of proto-oncogenes can lead to cancer. Reason (R): Mutated proto-oncogenes become oncogenes that promote uncontrolled division.
- Assertion (A): An increase in gene distance increases recombination frequency. Reason (R): Crossing over occurs more frequently between distant genes.
- Assertion (A): Failure of cell cycle checkpoints can lead to tumour formation. Reason (R): Cells continue dividing without differentiation or control.
- Assertion (A): Low recombination frequency indicates strong linkage. Reason (R): Genes located close together are less likely to be separated by crossing over.
- Assertion (A): Loss of tumour suppressor gene function leads to uncontrolled cell division. Reason (R): These genes normally inhibit cell cycle progression.
- Assertion (A): Exchange of genetic material between homologous chromosomes increases variation. Reason (R): It produces new combinations of alleles in gametes.
- Assertion (A): Gene mapping provides exact physical distances between genes. Reason (R): It is based on recombination frequency rather than actual DNA length.
- Assertion (A): Biopsy is the most confirmatory method for cancer diagnosis. Reason (R): It involves microscopic examination of tissue samples.
- Assertion (A): Environmental factors alone are responsible for cancer. Reason (R): Genetic mutations also contribute to cancer development.
- Assertion (A): Crossing over contributes more to genetic variation than linkage. Reason (R): Linkage tends to preserve parental combinations of genes.
- Assertion (A): Gene mapping is based on recombination frequency between genes. Reason (R): Greater recombination frequency indicates greater gene distance.
- Assertion (A): Counting parental and recombinant offspring helps in gene mapping. Reason (R): It allows calculation of recombination frequency.
- Assertion (A): Models using threads or beads can demonstrate crossing over. Reason (R): Exchange of segments can be visually represented to show recombination.
- Assertion (A): Metastasis refers to the spread of cancer cells to other parts of the body. Reason (R): Cancer cells can travel through blood or lymph to form secondary tumours.
Fill in the blank: Genes located on the same chromosome and inherited together are called ______ genes.
Fill in the blank: The exchange of genetic material between homologous chromosomes is known as ______.
Fill in the blank: The unit used to measure distance between genes on a chromosome is called ______.
Fill in the blank: The tendency of genes on the same chromosome to remain together during inheritance is called ______.
Fill in the blank: The formation of new gene combinations during meiosis occurs due to ______.
Fill in the blank: Substances that can cause cancer are known as ______.
Fill in the blank: If two genes are located very close to each other on a chromosome, they will show ______ linkage.
Fill in the blank: When control of the cell cycle fails, it results in the formation of a ______.
Fill in the blank: A mutation in proto-oncogenes can convert them into ______.
Fill in the blank: A decrease in recombination frequency indicates ______ linkage between genes.
Fill in the blank: The mixing of maternal and paternal gene segments occurs due to ______.
Fill in the blank: Failure of tumour suppressor genes leads to ______ cell division.
Fill in the blank: The statement “linkage is an exception to Mendel’s law” refers to the law of ______.
Fill in the blank: The most confirmatory method for cancer diagnosis is ______.
Fill in the blank: Genes that normally regulate cell growth but become cancer-causing after mutation are called ______.
Fill in the blank: A diagram showing relative positions of genes on a chromosome is called a ______ map.
Fill in the blank: The spread of cancer cells from one part of the body to another is known as ______.
Fill in the blank: The process by which cancer develops due to mutations is called ______.
9.11 Check Your Concepts
Why is linkage described as an exception to Mendel’s law of independent assortment rather than as a contradiction of it?
Why can the number of linkage groups in a species never exceed its haploid chromosome number?
A student states that a chromosome with more genes must show a higher recombination frequency between any two of its genes. Explain what is wrong with this reasoning.
Why must homologous chromosomes undergo synapsis before crossing over can occur?
What would happen to the genetic composition of gametes if chiasmata failed to form during prophase I of meiosis?
Explain why an exchange between two sister chromatids produces no recombinant offspring, while an exchange between non-sister chromatids does.
Crossing over involves the breakage and rejoining of chromatids, yet no genetic material is gained or lost. Explain how both statements can be true at the same time.
Why does a high crossing over value between two genes on the same chromosome make them behave almost as though they were on different chromosomes?
Two genes on the same chromosome show a crossing over value of 48%. What difficulty would a geneticist face in proving that they are linked at all, and how might data from a third gene lying between them help?
Arrange the following steps of crossing over in the correct sequence: breakage at corresponding points on non-sister chromatids; separation of chromatids at anaphase; pairing of homologous chromosomes by synapsis; rejoining of the broken segments with the opposite chromatid; formation of chiasmata; formation of gametes carrying new gene combinations.
Arrange the following steps of gene map construction in the correct order: convert each percentage into map units; place the outermost pair at the two ends; calculate the crossing over value for each pair of genes; check that the shorter distances add up to the largest; count parental and recombinant offspring; identify the largest crossing over value.
Draw a labelled diagram of a bivalent in prophase I showing a chiasma. Label the homologous chromosomes, sister chromatids, non-sister chromatids and the exchanged segments.
Draw a labelled diagram of the cell cycle marking the G1–S and G2–M checkpoints, and indicate on it the point at which failure leads to tumour formation.
Compare parental types and recombinant types with respect to their allele combinations, their origin and their relative numbers when two genes are closely linked.
Distinguish between a benign tumour and a malignant tumour with respect to growth, spread and outcome after removal.
Compare the behaviour of a cancer-causing DNA virus in permissive cells and in non-permissive cells, and explain why only one of the two situations leads to cancer.
Compare oncogenes and tumour suppressor genes with respect to their normal role, the type of change that leads to cancer, and the number of copies that usually have to be affected.
Match the scientists in Column I with their contributions in Column II. | Column I | Column II | |—|—| | a. Bateson and Punnett | i. Discovered a tumour-inducing virus in chickens | | b. T. H. Morgan | ii. Introduced the concept of linkage groups | | c. Sutton | iii. Described the coupling of factors in sweet pea | | d. Peyton Rous | iv. Showed that genes similar to viral cancer genes exist in normal cells | | e. Varmus and Bishop | v. Explained linkage clearly using Drosophila |
Match the terms in Column I with the descriptions in Column II. | Column I | Column II | |—|—| | a. Centimorgan | i. Point of exchange between non-sister chromatids | | b. Chiasma | ii. Substance in blood whose raised level may indicate cancer | | c. Metastasis | iii. Distance showing 1% recombination | | d. Carcinogenesis | iv. Gradual conversion of a normal cell into a cancerous cell | | e. Tumour marker | v. Spread of cancer cells to distant organs |
Why does the risk of cancer increase with age even in a person who has never been exposed to a known carcinogen?
What happens to a cell that carries damaged DNA if the G1–S checkpoint fails to function? Trace the consequences step by step.
Explain why a tumour can damage the body even before any of its cells have spread to another organ.
Why is a proto-oncogene not considered a harmful gene, even though its mutated form causes cancer?
The absence of introns in a v-onc gene is treated as evidence that the virus obtained the gene from a host cell. Explain the reasoning behind this conclusion.
A person inherits one faulty copy of a tumour suppressor gene yet remains healthy for many years. Explain why, and state how their risk differs from that of a person with two intact copies.
Arrange the following diagnostic steps in the usual order in which they are carried out, and state which one provides confirmation: biopsy and microscopic examination; imaging by CT or MRI; physical examination for lumps and swelling; blood tests for tumour markers.
A student concludes that radiation cannot be used to treat cancer because radiation is itself listed as a cause of cancer. Identify the flaw in this argument and correct it.
A student calculates the crossing over value by dividing the number of recombinant offspring by the number of parental offspring and multiplying by 100. Identify the error in this procedure and state the correct method.
A student obtains the values D–E = 12%, E–F = 9% and D–F = 21%, and draws the map with E at one end. Identify the mistake in the arrangement and redraw the map correctly, justifying your order.
A student proposes to test a new hormone therapy on every patient diagnosed with cancer, whatever the organ involved. Explain why this plan is unsound, and state what information must be obtained first.
Who first clearly explained the concept of linkage?
What is the term for a group of genes present on the same chromosome?
Name the virus discovered by Peyton Rous that can cause tumours.
Why do genes located far apart on the same chromosome show weaker linkage?
What is the role of cyclins in the cell cycle?
Why are proto-oncogenes important in normal cells?
How would recombination frequency change if the distance between two genes increases?
What would happen if DNA from a virus integrates into the host genome?
How can exposure to radiation influence the risk of cancer?
Why is crossing over able to separate genes that are linked?
How does crossing over lead to variation in offspring?
What is the consequence of loss of function in tumour suppressor genes?
Why is gene mapping considered an approximate method rather than an exact one?
Which contributes more to variation — linkage or crossing over? Justify briefly.
Why is biopsy considered essential for confirming cancer?
Suggest a method to demonstrate linkage using any organism.
How would you design an experiment to estimate the distance between two genes?
Explain a way to demonstrate metastasis using a simple classroom model.
Aditi is preparing a timeline of genetic discoveries. She wants to include the scientists who predicted linkage before it was experimentally explained. Identify these scientists and state their contribution.
Pooja is studying cancer biology and comes across genes that inhibit cell division. Identify these genes and state their role.
Ritesh learns that genes on the same chromosome do not always stay together, and is confused about how this is possible. Explain how crossing over affects linkage between genes.
Snehal studies cell cycle checkpoints and observes that failure at these points leads to abnormal growth. Explain why checkpoint failure results in tumour formation.
Farhan notices that recombination frequency varies across a chromosome and is higher towards its ends. Explain this observation.
Neeraj observes two genes showing 5% recombination frequency. He wants to estimate their relative position on a chromosome map. Apply the concept of gene mapping to interpret this result.
Ishika studies a case where two traits are almost always inherited together and suspects strong linkage. How can she use genetic crosses to confirm her assumption?
Varun reads about chemical carcinogens like benzene and wants to understand their effect. Explain how such chemicals may lead to cancer.
Garima examines a genetic cross and finds fewer recombinant types than expected. Analyse what this indicates about the genes involved.
Arpit claims that crossing over always breaks linkage completely. Evaluate this statement with justification.
Nisha believes that all viruses directly destroy cells to cause disease. Evaluate this statement in the context of cancer-causing viruses.
Siddharth argues that environmental factors alone are responsible for cancer. Evaluate this claim considering genetic factors.
In a genetic experiment, Ritu observes the following recombination frequencies between three genes: A–B = 8%, B–C = 12%, and A–C = 20%. Using this data, construct a gene map showing the relative positions of genes A, B and C. Identify the correct sequence of genes on the chromosome and justify your arrangement.
Arvind studies four genes (P, Q, R, S) and records recombination frequencies as follows: P–Q = 5%, Q–R = 7%, R–S = 6% and P–S = 18%. Construct a gene map indicating the order and distances between these genes. Explain how you determined the correct arrangement.
Sneha obtains recombination values between three genes as follows: X–Y = 10%, Y–Z = 15%, and X–Z = 5%. Analyse the data carefully and construct a gene map. Identify any inconsistency and explain how double crossing over might affect the observed values.
Meghana wants to prepare a classroom activity to demonstrate recombination using coloured threads as chromosomes. Explain how she can show crossing over effectively.
Rohanveer plans to construct a simple gene map using hypothetical data from a cross. Explain how he can organise the data and represent gene positions.
Lavanya is designing an awareness poster on cancer prevention. How can she include genetic and environmental factors clearly in her presentation?
Aarushi is preparing a presentation on early genetic concepts and wants to include how linkage was first proposed and later explained. She needs to identify the scientists involved and the organism used for experimental verification. Describe these contributions clearly and explain their significance in genetics.
Dev is making notes on chromosome mapping and wants to include the basic unit of measurement and its definition. He also needs to recall how recombination frequency is related to gene distance. State these concepts accurately with proper terminology.
Yashika is studying cancer genetics and comes across different types of genes involved in cell division. Identify these gene types and briefly describe their functions.
Raghavendra learns that genes located on the same chromosome may not always be inherited together, and thinks this contradicts linkage. Explain how crossing over modifies linkage and leads to new gene combinations.
Sanya studies tumour formation and reads that normal cells divide in a controlled manner. Explain the role of cell cycle regulation and what happens when it fails.
Imran observes that recombination frequency is used to construct gene maps but is not always perfectly accurate. Explain why recombination frequency may vary and how this affects mapping results.
Keshav performs a genetic cross and finds that two genes show 20% recombination frequency. He wants to place them on a chromosome map. Use the concept of the centimorgan to explain how he can determine their relative positions.
Pallak studies a case where a viral infection leads to uncontrolled cell growth. Describe how viral genetic material can alter normal cell regulation.
Harleen is given data from a cross showing mostly parental combinations and very few recombinants. She is asked to interpret the strength of linkage present. Discuss the genetic principles that explain her conclusion.
Zeeshan compares organisms in which crossing over is frequent with those in which it is absent, and observes differences in genetic variation. Discuss how the presence or absence of crossing over affects inheritance patterns.
Arnavraj examines linkage data and notices that some genes show strong association while others do not. Describe how gene distance and chromosome structure influence this observation.
Tanushree argues that gene mapping provides exact locations of genes on chromosomes. Her teacher disagrees. Explain this by discussing the limitations of gene mapping techniques.
Farida believes that only inherited mutations are responsible for cancer development. Her classmate suggests environmental factors are equally important. Explain both viewpoints with reasoning.
Prateek suggests that stronger linkage always benefits organisms by preserving traits. Explain this statement considering the role of variation in evolution.
Dhriti wants to create a classroom demonstration to show linkage and recombination using coloured beads and strings. Mention an activity that can clearly show both linked inheritance and crossing over.
Aftab plans to prepare a model illustrating how oncogenes and tumour suppressor genes interact in cancer development. Explain how he can visually represent this interaction for better understanding.
Rupali is designing a project to explain gene mapping using hypothetical recombination data. Explain how she can organise the data and construct a simple chromosome map.
9.12 Case-Based Questions
- A plant breeder is working with a wild variety of tomato that carries a gene for resistance to a fungal disease. Unfortunately, the same chromosome also carries a gene that gives the fruit a bitter taste, and in cross after cross the two traits arrive together in the offspring. Out of 500 plants raised from one cross, only 12 were resistant without being bitter. The breeder wants to move the resistance gene into a cultivated variety without carrying the bitterness along with it.
- Explain why the two traits keep arriving together in the offspring.
- Name and describe the process that produced the 12 exceptional plants.
- Calculate the crossing over value between the two genes and express it in map units.
- Would the breeder’s task be easier or harder if the two genes were separated by 30 map units? Justify your answer.
- A group of students is given data from three separate crosses involving genes G, H and K, all located on the same chromosome. The recombination frequencies recorded are G–H = 4%, H–K = 11% and G–K = 15%. One student begins by drawing the three genes in the order in which they are listed in the data table.
- Explain why the order in which genes are listed in a data table has no bearing on their order on the chromosome.
- Determine the correct order of G, H and K, and justify your reasoning.
- Draw the gene map with the distances marked in map units.
- State two reasons why the distances on this map should be treated as approximate.
- A 58-year-old patient visits a hospital complaining of unexplained weight loss and persistent fatigue. On examination the doctor finds a firm lump in the abdomen. A CT scan shows a mass of about 4 cm confined to a single organ, and a blood test shows a raised level of a particular protein associated with tumours of that organ. The doctor nevertheless does not begin treatment, and instead orders one further procedure.
- Name the further procedure the doctor is most likely to have ordered.
- Explain why the scan and the blood test together are still not sufficient for a diagnosis.
- State what the doctor expects to see under the microscope if the mass is cancerous.
- The report describes the mass as confined to one organ with no evidence of spread. How does this finding influence the choice of treatment?
- Workers at an old insulation factory handled asbestos daily for many years, often without protective equipment. The factory closed thirty years ago. Recently an unusually high number of former workers from that factory have been diagnosed with cancer of the chest lining, and their families are seeking compensation. The company argues that no link can be proved after such a long gap.
- Classify asbestos as a carcinogen and explain how such an agent leads to cancer at the level of the gene.
- Explain why cancers caused by chemical carcinogens often appear decades after exposure.
- Discuss the difficulty that this long delay creates in establishing responsibility.
- Suggest two safeguards that could have reduced the risk to these workers.
- A research team studies two cell cultures infected with the same DNA virus. In the first culture, virus particles multiply rapidly, the cells burst and die, and large amounts of virus are released into the medium. In the second culture, no new virus particles are produced, the cells survive, but after several weeks they begin to divide in a disorganised heap instead of a neat single layer.
- Identify the type of cell used in each culture.
- Explain what has happened to the viral DNA in the second culture.
- Explain why the second culture, and not the first, represents a step towards cancer.
- Name one virus that can bring about the change seen in the second culture.
- Two members of the same family are found to carry mutations affecting genes that control cell division. In the first, a gene that normally provides signals for cell growth has been altered so that it now signals continuously. In the second, both copies of a gene whose product normally halts the cycle when DNA is damaged have been inactivated. Both individuals develop tumours, though at different ages.
- Name the class of gene affected in each individual.
- State whether each change represents a gain of function or a loss of function.
- Explain why one damaged copy was enough in the first case, while both copies had to be lost in the second.
- Explain, using this example, why cancer is described as arising from either a jammed accelerator or failed brakes.
- A pathologist examines two stained tissue sections from the same organ of a patient. In the first section the cells are uniform in size and regularly arranged, and very few are seen in mitosis. In the second, the cells are crowded and irregular, many have enlarged nuclei, and a large proportion are caught in the act of dividing. The pathologist also notes that cells resembling those of the second section have been found in a lymph node some distance away.
- Identify which section is from normal tissue and which from tumour tissue, giving your reasons.
- Explain what the high proportion of dividing cells indicates about the control of the cell cycle in that tissue.
- Name the process by which cells have reached the distant lymph node, and state the two routes by which they may have travelled.
- Explain how this last finding changes the seriousness of the patient’s condition.
- A patient with an advanced cancer is placed on a drug that kills rapidly dividing cells. Within three weeks the tumour has shrunk noticeably, but the patient has lost much of her hair, feels persistently nauseous, and her blood counts have fallen. Her doctor explains that a newer drug is available which acts on a particular abnormal protein produced by her tumour cells, and that a test would first be needed to establish whether her tumour carries that target.
- Name the treatment the patient is currently receiving and explain the principle on which it works.
- Explain why hair loss, nausea and low blood counts follow from that principle.
- Name the newer form of treatment being suggested and explain why it causes fewer side effects.
- Explain why a test on the tumour is necessary before the newer treatment can be started.
- Mehul is preparing for his biology examination and revises the concept that genes located on the same chromosome tend to be inherited together. While studying a genetic cross, he notices that certain traits always appear together in the offspring. He recalls that this phenomenon was first predicted before being experimentally explained later. He also remembers that chromosomes carry multiple genes arranged linearly.
- Name the term used for genes inherited together.
- Who first clearly explained this concept experimentally?
- What is the term for a group of genes present on the same chromosome?
- State one characteristic of gene arrangement on chromosomes.
- Kavya is revising cancer biology and learns that cell division is tightly regulated in normal cells. She reads that certain genes help control the rate of cell division while others promote growth, and that mutations can disturb this balance and lead to disease. She also notes that some substances can trigger such mutations.
- What are substances that cause cancer called?
- Name the genes that normally promote cell division.
- What are these genes called after mutation?
- Identify the genes that prevent uncontrolled cell division.
- Rohit observes that two traits in pea plants are usually inherited together, but sometimes new combinations appear in the offspring. He is confused because this seems to contradict the concept of linkage. His teacher explains that a process during meiosis can separate linked genes, and that the distance between genes affects this phenomenon.
- Name the process that causes separation of linked genes.
- Explain why genes far apart show weaker linkage.
- What is the effect of this process on genetic variation?
- How does this relate to Mendel’s law of independent assortment?
- Aisha studies how normal cells maintain control over their division through checkpoints in the cell cycle. She learns that failure of these checkpoints can lead to uncontrolled growth. She also reads about tumours and how they affect surrounding tissues, and her teacher explains that multiple factors, environmental and genetic, are involved.
- What happens when cell cycle checkpoints fail?
- Define tumour formation.
- Name one environmental factor causing cancer.
- Explain why cancer development is gradual.
- Aditya performs a genetic cross in a laboratory and observes that two genes show only 5% recombination frequency. He recalls that recombination frequency is used to determine gene distance, and that genes located close to each other tend to be inherited together. Based on this data, he tries to interpret the relationship between these genes.
- What does 5% recombination indicate about gene distance?
- How strong is the linkage shown in this case?
- Express this distance in map units.
- Predict what would happen if the gene distance increased.
- Simran studies a case where a viral infection leads to abnormal cell growth. She learns that some viruses integrate their DNA into the host genome, which disrupts the normal regulation of cell division and may lead to cancer. She also understands that certain genes get activated abnormally in this process.
- What happens when viral DNA integrates into host DNA?
- Which type of genes may get activated abnormally?
- What is the term for cancer-causing genes?
- Name one example of a cancer-causing virus.
- Neeraj compares two genetic crosses. In one cross most offspring resemble the parental types, while in the other many new combinations are observed. He analyses that the difference may be due to the distance between the genes, and considers the role of crossing over in generating variation.
- What does a high number of parental types indicate?
- What does a high number of recombinants indicate?
- How does gene distance influence recombination frequency?
- Explain the role of crossing over in variation.
- Pooja studies cancer progression and notices that two types of genes are involved — those that promote cell division and those that inhibit it. She finds that mutations in both types can lead to cancer, and analyses how their roles differ but ultimately contribute to the same outcome.
- Differentiate between proto-oncogenes and tumour suppressor genes.
- What happens when proto-oncogenes mutate?
- What is the effect of loss of tumour suppressor genes?
- How do both contribute to cancer development?
- Arvind argues that gene mapping gives the exact position of genes on chromosomes. His teacher disagrees and explains that gene mapping is based on recombination frequency, and that several factors can affect recombination rates. Arvind evaluates both viewpoints to understand the limitations of gene mapping.
- Why is gene mapping considered approximate?
- What is the basis of gene mapping?
- Mention one factor affecting recombination frequency.
- Evaluate the accuracy of gene mapping techniques.
- Nisha believes that environmental factors alone are responsible for cancer development. Another student argues that genetic mutations also play a major role. The teacher explains that both factors interact in complex ways, and examples of radiation, chemicals and inherited susceptibility are discussed.
- State one environmental factor causing cancer.
- What role do genetic mutations play in cancer?
- Why is it incorrect to blame only environmental factors?
- Give a justified conclusion about cancer causation.
- Yuvraj plans to demonstrate crossing over in a classroom using simple materials. He decides to use coloured threads to represent homologous chromosomes, and by twisting and exchanging segments he wants to show how recombination occurs. He also aims to explain how new gene combinations arise.
- How can coloured threads represent chromosomes?
- How will crossing over be demonstrated?
- What outcome will this activity show?
- How will this help in understanding genetic variation?
- Tanisha is designing a project to explain gene mapping using hypothetical recombination data. She collects values for recombination frequency between different gene pairs and plans to arrange them in a linear order to represent their positions. She also wants to explain the concept of map units.
- What data is required to construct a gene map?
- How are genes arranged using recombination frequency?
- What is a centimorgan?
- How can this model help in predicting inheritance patterns?
9.13 Practice With Data
In a test cross involving two linked genes, 1200 offspring were obtained. Of these, 1104 showed the parental combinations and the rest showed new combinations. Calculate the crossing over value between the two genes and state the distance between them in map units.
A cross involving genes for body colour and wing shape produced the following offspring.
| Phenotype class | Number of individuals |
|---|---|
| Grey body, long wing (parental) | 452 |
| Black body, short wing (parental) | 438 |
| Grey body, short wing (recombinant) | 56 |
| Black body, long wing (recombinant) | 54 |
- Calculate the total number of offspring scored.
- Calculate the crossing over value between the two genes.
- State the distance between the genes in centimorgans and comment on the strength of the linkage.
Three genes on a chromosome give the following crossing over values: R–S = 6%, S–T = 14%, R–T = 20%. Determine the order of the three genes, construct the gene map with distances marked, and justify your arrangement.
Four genes W, X, Y and Z lie on one chromosome. The recorded values are W–X = 3%, X–Y = 9%, Y–Z = 5% and W–Z = 17%. Construct the gene map showing the order and the distance between each adjacent pair of genes, and show that your arrangement is consistent with all four values.
For three genes the values obtained are A–B = 18%, B–C = 14% and A–C = 28%. Construct the map, calculate the difference between the sum of the two shorter distances and the observed largest value, and explain what this difference indicates about crossovers occurring between A and C.
In one experiment two genes were separated in 462 out of 1050 offspring. Calculate the crossing over value. State, with reasons, whether these genes can be reliably mapped using this value alone.
The table below gives the diploid chromosome number of four species. Complete the table by calculating the number of linkage groups in each, and state the rule you have applied.
| Species | Diploid number (\(2n\)) | Number of linkage groups |
|---|---|---|
| Onion | 16 | ? |
| Rice | 24 | ? |
| Cat | 38 | ? |
| Housefly | 12 | ? |
- A graph is plotted with the distance between gene pairs in map units on the x-axis and the observed recombination frequency on the y-axis. The plot rises in a straight line for values up to about 10 map units, but then begins to flatten and never rises above 50%.
- State what the straight portion of the graph shows about the relationship between distance and recombination frequency.
- Explain why the curve begins to flatten at larger distances.
- Explain why the curve never exceeds 50%.
In a stained preparation of normal tissue, 24 of 800 cells in the field were in mitosis. In a preparation from a tumour of the same organ, 96 of 640 cells were in mitosis. Calculate the mitotic index of each sample and comment on what the difference indicates about the control of the cell cycle in the tumour tissue.
Two tissue samples give mitotic index values of 0.02 and 0.15 respectively. If a field of view in the second sample contains 340 cells, calculate how many of them would be expected to be in mitosis, and state what a rising mitotic index in successive samples from the same patient would suggest.
The level of a tumour marker in a patient’s blood is monitored during treatment and recorded as follows.
| Week of treatment | Marker level (units per ml) |
|---|---|
| 0 | 88 |
| 4 | 51 |
| 8 | 24 |
| 12 | 9 |
| 20 | 37 |
- Describe the trend shown between week 0 and week 12 and state what it suggests about the response to treatment.
- Calculate the percentage fall in the marker level between week 0 and week 12.
- Comment on the reading at week 20 and state what further step the doctor is likely to take before drawing any conclusion.
- In a mapping experiment, a total of 2000 offspring were scored for three genes. Between the outer genes, 240 offspring were recombinant for the left-hand interval and 160 for the right-hand interval. Calculate the crossing over value for each interval, state the total map distance between the two outer genes, and explain why the value actually observed between the outer genes is likely to be slightly lower than this total.