Opened by G.T. Morgan and his students in 1911-1926. They proved that Mendel's III law requires additions: hereditary inclinations are not always inherited independently, sometimes they are transmitted in whole groups - they are linked to each other. The established patterns of the location of genes in chromosomes contributed to the elucidation of the cytological mechanisms of the laws of Gregor Mendel and the development of the genetic foundations of the theory natural selection. Such groups can move to another homologous chromosome when conjugated during prophase 1 of meiosis.

Provisions of the chromosome theory:

• 1) The transmission of hereditary information is associated with chromosomes, in which genes lie linearly, at certain loci.
• 2) Each gene of one homologous chromosome corresponds to an allelic gene of another homologous chromosome.
• 3) Allelic genes can be the same in homozygotes and different in heterozygotes.
• 4) Each individual in the population contains only 2 alleles, and gametes - one allele.
• 5) In the phenotype, the trait manifests itself in the presence of 2 allelic genes.
• 6) The degree of dominance in multiple alleles increases from extreme recessive to extreme dominant. For example, in a rabbit, coat color depends on the recessive gene "c" - the gene for albinism. Dominant in relation to "c" will be the gene "ch "" - Himalayan (ermine) color - white body, single eyes, dark tips of the nose, ears, tail and limbs. Dominant in relation to "ch" will be the gene "chc" - chinchilla - light gray. Even more dominant will be the "ca" gene - agouti, dark color. The most dominant will be the C gene - black color, it dominates all alleles - C, ca, chc, ch, s.
• 7) Dominance and recessiveness of alleles are not absolute, but relative. The same trait can be inherited in a dominant OR recessive manner. For example, the inheritance of epicanthus in Negroids is dominant, in Mongoloids it is recessive, in Caucasians this allele is absent. Newly emerging alleles are recessive. The old ones are dominant.
• 8) Each pair of chromosomes is characterized by a certain set of genes that make up linkage groups, often inherited together.
• 9) The number of linkage groups is equal to the number of chromosomes in the haploid set.
• 10) The movement of genes from one homologous chromosome to another in prophase 1 of meiosis occurs at a certain frequency, which is inversely proportional to the distance between the genes - the smaller the distance between the genes, the greater the adhesion force between them, and vice versa.
• 11) The unit of distance between genes is the morganide, which is equal to 1% of crossover offspring. For example, the gene for the Rh factor and the gene for ovalocytosis are located 3 morganids apart, and the gene for color blindness and hemophilia is 10 morganids apart.

The provisions of the chromosome theory were proved cytologically and experimentally by Morgan on the fruit fly Drosophila.

The inheritance of traits whose genes are located on the X and Y sex chromosomes is called sex-linked inheritance. For example, in humans, the recessive genes for color blindness and hemophilia are located on the X sex chromosome. Consider the inheritance of hemophilia in humans:

h - gene for hemophilia (bleeding);

H - gene for normal blood clotting.

The recessive trait is manifested in boys, in girls it is suppressed by the allelic dominant H-gene.

Inheritance of a trait occurs crosswise - from sex to sex, from mother to sons, from father to daughters.

The external manifestation of a trait - the phenotype - depends on several conditions:

• 1) the presence of 2 hereditary deposits from both parents;
• 2) on the way of interaction between allelic genes (dominant, recessive, co-dominance);
• 3) on the conditions of interaction between non-allelic genes (complementary, epistatic interaction, polymerism, pleiotropy);
• 4) from the location of the gene (in the autosome or sex chromosome);
• 5)on conditions external environment.

Linked inheritance. Chromosomal theory of heredity.

Chromosomal theory of heredity.

The main provisions of the chromosome theory of heredity. Chromosomal analysis.

Formation of the chromosome theory. In 1902-1903. American cytologist W. Setton and German cytologist and embryologist T. Boveri independently revealed parallelism in the behavior of genes and chromosomes during the formation of gametes and fertilization. These observations formed the basis for the assumption that genes are located on chromosomes. However, experimental proof of the localization of specific genes in specific chromosomes was obtained only in 1910 by the American geneticist T. Morgan, who in subsequent years (1911-1926) substantiated the chromosome theory of heredity. According to this theory, the transmission of hereditary information is associated with chromosomes, in which genes are localized linearly, in a certain sequence. Thus, it is the chromosomes that are the material basis of heredity.

Chromosomal theory of heredity- the theory according to which the chromosomes enclosed in the nucleus of the cell are carriers of genes and represent the material basis of heredity, that is, the continuity of the properties of organisms in a number of generations is determined by the continuity of their chromosomes. The chromosome theory of heredity arose in the early 20th century. based on cellular theory and was used to study the hereditary properties of organisms of hybridological analysis.

The main provisions of the chromosome theory of heredity.

1. Genes are located on chromosomes. Moreover, different chromosomes contain an unequal number of genes. In addition, the set of genes for each of the non-homologous chromosomes is unique.

2. Allelic genes occupy the same loci in homologous chromosomes.

3. Genes are located on the chromosome in a linear sequence.

4. The genes of one chromosome form a linkage group, that is, they are inherited predominantly linked (jointly), due to which the linked inheritance of some traits occurs. The number of linkage groups is equal to the haploid number of chromosomes of a given species (in the homogametic sex) or more by 1 (in the heterogametic sex).

5. Linkage is broken as a result of crossing over, the frequency of which is directly proportional to the distance between genes in the chromosome (therefore, the strength of linkage is inversely related to the distance between genes).

6. Everyone species characterized by a certain set of chromosomes - karyotype.

Linked inheritance

The independent combination of traits (Mendel's third law) is carried out on the condition that the genes that determine these traits are in different pairs of homologous chromosomes. Therefore, in each organism, the number of genes that can independently combine in meiosis is limited by the number of chromosomes. However, in an organism, the number of genes significantly exceeds the number of chromosomes. For example, before the era of molecular biology, more than 500 genes were studied in corn, more than 1 thousand in the Drosophila fly, and about 2 thousand genes in humans, while they have 10, 4 and 23 pairs of chromosomes, respectively. The fact that the number of genes in higher organisms is several thousand was already clear to W. Setton at the beginning of the 20th century. This gave reason to assume that many genes are localized in each chromosome. Genes located on the same chromosome form a linkage group and are inherited together.

T. Morgan proposed to call the joint inheritance of genes linked inheritance. The number of linkage groups corresponds to the haploid number of chromosomes, since the linkage group consists of two homologous chromosomes in which the same genes are localized. (In individuals of the heterogametic sex, for example, in male mammals, there are actually one more linkage groups, since the X and Y chromosomes contain different genes and represent two different linkage groups. Thus, women have 23 linkage groups, and men have 24).

The mode of inheritance of linked genes differs from the inheritance of genes located in different pairs of homologous chromosomes. So, if, with independent combination, a diheterozygous individual forms four types of gametes (AB, Ab, aB and ab) in equal quantities, then with linked inheritance (in the absence of crossing over), the same diheterozygote forms only two types of gametes: (AB and ab) also in equal amounts. The latter repeat the combination of genes in the parent's chromosome.

It was found, however, that in addition to ordinary (non-crossover) gametes, other (crossover) gametes also arise with new combinations of genes - Ab and aB, which differ from the combinations of genes in the parent's chromosomes. The reason for the emergence of such gametes is the exchange of sections of homologous chromosomes, or crossing over.

Crossing over occurs in prophase I of meiosis during conjugation of homologous chromosomes. At this time, parts of two chromosomes can cross over and exchange their parts. As a result, qualitatively new chromosomes arise, containing sections (genes) of both maternal and paternal chromosomes. Individuals that are obtained from such gametes with a new combination of alleles are called crossing-over or recombinant.

The frequency (percentage) of crossover between two genes located on the same chromosome is proportional to the distance between them. Crossing over between two genes occurs less frequently the closer they are to each other. As the distance between genes increases, the likelihood that crossing over will separate them on two different homologous chromosomes increases more and more.

The distance between genes characterizes the strength of their linkage. There are genes with a high percentage clutch and those where the clutch is almost not detected. However, with linked inheritance, the maximum crossover frequency does not exceed 50%. If it is higher, then there is a free combination between pairs of alleles, indistinguishable from independent inheritance.

biological significance crossing over is extremely large, since genetic recombination allows you to create new, previously non-existing combinations of genes and thereby increase hereditary variability, which gives ample opportunities for adaptation of the body to various conditions environment. A person specifically conducts hybridization in order to obtain the necessary combinations for use in breeding work.

Coupling and crossing over. From the principles of genetic analysis outlined in the previous chapters, it clearly follows that an independent combination of traits can occur only if the genes that determine these traits are located on nonhomologous chromosomes. Consequently, in each organism, the number of pairs of traits for which independent inheritance is observed is limited by the number of pairs of chromosomes. On the other hand, it is obvious that the number of characteristics and properties of an organism controlled by genes is extremely large, and the number of pairs of chromosomes in each species is relatively small and constant.

It remains to be assumed that each chromosome contains not one gene, but many. If so, then Mendel's third law concerns the distribution of chromosomes, not genes, i.e., its effect is limited.

The phenomenon of linked inheritance. From Mendel's third law it follows that when crossing forms that differ in two pairs of genes (AB and ab), get a hybrid AaBb, producing four kinds of gametes AB, Ab, aB and ab in equal amounts.

In accordance with this, splitting 1: 1: 1: 1 is carried out in the analyzing cross, i.e. combinations of features characteristic of parent forms (AB and ab), occur with the same frequency as new combinations (Ab and aB),- 25% each. However, as the facts accumulated, geneticists increasingly began to encounter deviations from independent inheritance. In some cases, new combinations of features (Ab and aB) in Fb completely absent - observed full grip between the genes of the original forms. But more often, parental combinations of traits prevailed in the offspring to one degree or another, and new combinations occurred with a lower frequency than expected with independent inheritance, i.e. less than 50%. Thus, in this case, the genes were more often inherited in the original combination (they were linked), but sometimes this linkage was broken, giving new combinations.

The joint inheritance of genes, which limits their free combination, Morgan proposed to call gene linkage or linked inheritance.

Crossing over and its genetic proof. If more than one gene is assumed to be located on the same chromosome, the question arises whether the alleles of one gene in a homologous pair of chromosomes can change places, moving from one homologous chromosome to another. If such a process did not occur, then the genes would be combined only by random segregation of non-homologous chromosomes in meiosis, and the genes that are in the same pair of homologous chromosomes would always be inherited in a linked group.

Research by T. Morgan and his school showed that genes are regularly exchanged in a homologous pair of chromosomes. The process of exchanging identical sections of homologous chromosomes with the genes contained in them is called chromosome crossing or crossing over. Crossing over provides new combinations of genes located on homologous chromosomes. The phenomenon of crossing over, as well as linkage, turned out to be common to all animals, plants, and microorganisms. The presence of an exchange of identical regions between homologous chromosomes ensures the exchange or recombination of genes and thereby significantly increases the role of combinative variability in evolution. The crossover of chromosomes can be judged by the frequency of occurrence of organisms with a new combination of characters. Such organisms are called recombinants.

Gametes with chromosomes that have undergone crossing over are called crossover, and with those that have not undergone crossing over, they are called non-crossover. Accordingly, organisms that have arisen from the combination of hybrid crossover gametes with analyzer gametes are called crossovers or recombinants, and those that have arisen due to non-crossover hybrid gametes are called non-crossover or non-recombinant.

Morgan's Coupling Law. In the analysis of splitting in the case of crossover, attention is drawn to a certain quantitative ratio of crossover and non-crossover classes. Both initial parental combinations of traits, formed from non-crossover gametes, are equal in the progeny of the analyzing cross. quantitatively. In this experiment with Drosophila, there were approximately 41.5% of both individuals. In total, non-crossover flies accounted for 83% of the total number of offspring. The two crossover classes are also the same in terms of the number of individuals, and their sum is 17%.

The frequency of crossing over does not depend on the allelic state of the genes involved in crossing. If flies and are used as a parent, then in analyzing crossing crossover ( b+vg and bvg +) and non-crossover ( bvg and b+vg+) individuals will appear with the same frequency (17 and 83%, respectively) as in the first case.

The results of these experiments show that gene linkage really exists, and only in a certain percentage of cases is it broken due to crossing over. Hence, it was concluded that between homologous chromosomes, a mutual exchange of identical sections can be carried out, as a result of which the genes located in these sections of paired chromosomes move from one homologous chromosome to another. The absence of crossover (full linkage) between genes is an exception and is known only in the heterogametic sex of a few species, for example, in Drosophila and the silkworm.

The linked inheritance of traits studied by Morgan was called Morgan's linkage law. Since recombination occurs between genes, and the gene itself is not separated by crossing over, it was considered a unit of crossing over.

Crossover value. The crossover value is measured by the ratio of the number of crossover individuals to the total number of individuals in the offspring from analyzing crosses. Recombination occurs reciprocally, i.e. mutual exchange is carried out between parental chromosomes; this obliges to count the crossover classes together as the result of a single event. The crossover value is expressed as a percentage. One percent of crossing over is a unit of distance between genes.

The linear arrangement of genes on a chromosome. T. Morgan suggested that genes are located linearly on chromosomes, and the frequency of crossing over reflects the relative distance between them: the more often crossing over occurs, the farther apart the genes are from each other in the chromosome; the less crossover, the closer they are to each other.

One of Morgan's classic experiments on Drosophila, proving the linear arrangement of genes, was the following. Females heterozygous for three linked recessive genes that determine the yellow body color y, white eye color w and forked wings bi, were crossed with males homozygous for these three genes. In the offspring, 1.2% of crossover flies were obtained, which arose from the crossover between genes at and w; 3.5% - from crossing over between genes w and bi and 4.7% between at and b.i.

From these data it clearly follows that the percentage of crossover is a function of the distance between genes. Since the distance between the extreme genes at and bi is equal to the sum of two distances between at and w, w and bi, it should be assumed that the genes are located sequentially on the chromosome, i.e. linearly.

The reproducibility of these results in repeated experiments indicates that the location of the genes in the chromosome is strictly fixed, i.e., each gene occupies its specific place in the chromosome - the locus.

The main provisions of the chromosomal theory of heredity - the pairing of alleles, their reduction in meiosis and the linear arrangement of genes in the chromosome - corresponds to a single-stranded model of the chromosome.

Single and multiple crosses. Having accepted the position that there can be many genes in the chromosome and they are located in the chromosome in a linear order, and each gene occupies a certain locus in the chromosome, Morgan admitted that the crossover between homologous chromosomes can occur simultaneously at several points. This assumption was also proved by him on Drosophila, and then completely confirmed on a number of other animals, as well as on plants and microorganisms.

Crossing over that occurs only in one place is called single, at two points at the same time - double, at three - triple, etc., i.e. it can be multiple.

The further apart the genes are on the chromosome, the greater the likelihood of double crossovers between them. The percentage of recombinations between two genes more accurately reflects the distance between them, the smaller it is, since in the case of a small distance, the possibility of double exchanges decreases.

To account for double crossing over, it is necessary to have an additional marker located between the two studied genes. The determination of the distance between genes is carried out as follows: to the sum of the percentages of single crossover classes, double the percentage of double crossovers is added. Doubling the percentage of double crossovers is necessary because each double crossover is due to two independent single breaks at two points.

Interference. It has been established that crossing over that occurs in one place on the chromosome suppresses crossing over in nearby regions. This phenomenon is called interference. With a double cross, interference is especially pronounced in the case of small distances between genes. Chromosome breaks are dependent on each other. The degree of this dependence is determined by the distance between the breaks that occur: as you move away from the break, the possibility of another break increases.

The effect of interference is measured by the ratio of the number of observed double discontinuities to the number of possible ones, assuming complete independence of each of the discontinuities.

gene localization. If the genes are located linearly on the chromosome, and the frequency of crossing over reflects the distance between them, then the location of the gene on the chromosome can be determined.

Before determining the position of a gene, i.e., its localization, it is necessary to determine on which chromosome this gene is located. Genes that are on the same chromosome and are inherited in a linked fashion make up a linkage group. It is obvious that the number of linkage groups in each species must correspond to the haploid set of chromosomes.

To date, linkage groups have been identified in the most genetically studied objects, and in all these cases a complete correspondence between the number of linkage groups and the haploid number of chromosomes has been found. Yes, corn Zea mays) the haploid set of chromosomes and the number of linkage groups are 10, in peas ( Pisum sativum) - 7, Drosophila melanogaster - 4, house mice ( Mus muscle) - 20, etc.

Since the gene occupies a certain place in the linkage group, this allows you to set the order of the genes in each chromosome and build genetic maps of chromosomes.

genetic maps. A genetic map of chromosomes is a diagram of the relative arrangement of genes in a given linkage group. They have so far been compiled only for some of the most genetically studied objects: Drosophila, corn, tomatoes, mice, neurospores, Escherichia coli, etc.

Genetic maps are made for each pair of homologous chromosomes. Clutch groups are numbered.

In order to map, it is necessary to study the patterns of inheritance of a large number of genes. In Drosophila, for example, more than 500 genes located in four linkage groups have been studied; in corn, more than 400 genes located in ten linkage groups, and so on. When compiling genetic maps, the linkage group, the full or abbreviated name of the genes, the distance in percent from one of the ends of the chromosome, taken as the zero point, are indicated; sometimes the site of the centromere is indicated.

In multicellular organisms, gene recombination is reciprocal. In microorganisms, it can be one-sided. So, in a number of bacteria, for example, in Escherichia coli ( Escherichia coli), transfer genetic information occurs during cell conjugation. The only chromosome of a bacterium, which has the shape of a closed ring, always breaks at a certain point during conjugation and passes from one cell to another.

The length of the transferred chromosome segment depends on the duration of conjugation. The sequence of genes in the chromosome is constant. Because of this, the distance between genes on such a ring map is measured not in percent of crossing over, but in minutes, which reflects the duration of conjugation.

Cytological evidence of crossing over. After genetic methods were able to establish the phenomenon of crossing over, it was necessary to obtain direct evidence of the exchange of sections of homologous chromosomes, accompanied by gene recombination. The patterns of chiasma observed in the prophase of meiosis can only serve as indirect evidence of this phenomenon; it is impossible to state the exchange that has taken place by direct observation, since the homologous chromosomes exchanging segments are usually absolutely the same in size and shape.

To compare cytological maps of giant chromosomes with genetic maps, Bridges suggested using the crossover coefficient. To do this, he divided the total length of all chromosomes of the salivary glands (1180 μm) by the total length of genetic maps (279 units). On average, this ratio was 4.2. Therefore, each unit of crossover on the genetic map corresponds to 4.2 microns on the cytological map (for the chromosomes of the salivary glands). Knowing the distance between genes on the genetic map of any chromosome, one can compare the relative frequency of crossover in its different regions. For example, in X- Drosophila chromosome genes at and ec are at a distance of 5.5%, therefore, the distance between them in the giant chromosome should be 4.2 μm X 5.5 = 23 μm, but direct measurement gives 30 μm. So in this area X-Chromosome crossing over is less than the average norm.

Due to the uneven implementation of exchanges along the length of chromosomes, when they are mapped, genes are distributed on it with different densities. Therefore, the distribution of genes on genetic maps can be considered as an indicator of the possibility of crossover along the length of the chromosome.

Crossover mechanism. Even before the discovery of the intersection of chromosomes by genetic methods, cytologists, studying the prophase of meiosis, observed the phenomenon of mutual wrapping of chromosomes, the formation of χ-shaped figures by them - chiasm (χ is the Greek letter "chi"). In 1909, F. Jansens suggested that chiasmata are associated with the exchange of chromosome regions. Subsequently, these pictures served as an additional argument in favor of the hypothesis of the genetic crossover of chromosomes put forward by T. Morgan in 1911.

The mechanism of chromosome crossing is associated with the behavior of homologous chromosomes in prophase I of meiosis.

Crossing over occurs at the stage of four chromatids and is confined to the formation of chiasmata.

If in one bivalent there was not one exchange, but two or more, then in this case several chiasmata are formed. Since there are four chromatids in the bivalent, then, obviously, each of them has an equal probability to exchange sites with any other. In this case, two, three or four chromatids can participate in the exchange.

The exchange within sister chromatids cannot lead to recombinations, since they are genetically identical, and because of this, such an exchange does not make sense as a biological mechanism of combinative variability.

Somatic (mitotic) crossing over. As already mentioned, crossing over occurs in prophase I of meiosis during the formation of gametes. However, there is a somatic, or mitotic, crossing over, which is carried out during the mitotic division of somatic cells, mainly embryonic tissues.

It is known that homologous chromosomes in the prophase of mitosis usually do not conjugate and are located independently of each other. However, sometimes it is possible to observe synapsis of homologous chromosomes and figures resembling chiasma, but no reduction in the number of chromosomes is observed.

Hypotheses about the mechanism of crossover. There are several hypotheses regarding the mechanism of crossover, but none of them fully explains the facts of gene recombination and the cytological patterns observed in this case.

According to the hypothesis proposed by F. Jansens and developed by C. Darlington, in the process of synapsis of homologous chromosomes in the bivalent, a dynamic tension is created that arises in connection with the spiralization of chromosome threads, as well as in the mutual wrapping of homologues in the bivalent. Due to this tension, one of the four chromatids breaks. The break, disturbing the balance in the bivalent, leads to a compensatory break at a strictly identical point in any other chromatid of the same bivalent. Then there is a reciprocal reunion of the broken ends, leading to crossing over. According to this hypothesis, chiasmata are directly related to crossing over.

According to the hypothesis of K. Sachs, chiasms are not the result of crossing over: first, chiasms are formed, and then an exchange occurs. With the divergence of chromosomes to the poles due to mechanical stress in the places of the chiasm, breaks and the exchange of the corresponding sections occur. After the exchange, the chiasm disappears.

The meaning of another hypothesis, proposed by D. Belling and modernized by I. Lederberg, is that the process of DNA replication can reciprocally switch from one strand to another; reproduction, starting on one template, switches from some point to the DNA template strand.

Factors affecting the crossover of chromosomes. Crossing over is influenced by many factors, both genetic and environmental. Therefore, in a real experiment, one can talk about the crossover frequency, bearing in mind all the conditions under which it was determined. Crossing over is practically absent between heteromorphic X- and Y-chromosomes. If it happened, then the chromosomal sex determination mechanism would be constantly destroyed. The blocking of crossing over between these chromosomes is associated not only with the difference in their size (it is not always observed), but also due to Y-specific nucleotide sequences. Required condition synapse of chromosomes (or their sections) - homology of nucleotide sequences.

The vast majority of higher eukaryotes are characterized by approximately the same frequency of crossing over in both the homogametic and heterogametic sexes. However, there are species in which crossing over is absent in individuals of the heterogametic sex, while in individuals of the homogametic sex it proceeds normally. This situation is observed in heterogametic Drosophila males and silkworm females. It is significant that the frequency of mitotic crossing over in these species in males and females is almost the same, which indicates different elements of control of individual stages of genetic recombination in germ and somatic cells. In heterochromatic regions, in particular pericentromeric regions, the frequency of crossing over is reduced, and therefore the true distance between genes in these regions can be changed.

Crossover-blocking genes discovered , but there are also genes that increase its frequency. They can sometimes induce a noticeable number of crossovers in Drosophila males. Chromosomal rearrangements, in particular inversions, can also act as crossover locks. They disrupt the normal conjugation of chromosomes in the zygotene.

It was found that the frequency of crossing over is influenced by the age of the organism, as well as exogenous factors: temperature, radiation, salt concentration, chemical mutagens, drugs, hormones. Under most of these influences, the frequency of crossing over increases.

In general, crossing over is one of the regular genetic processes controlled by many genes, both directly and through the physiological state of meiotic or mitotic cells. The frequency of various types of recombinations (meiotic, mitotic crossing over and sister, chromatid exchanges) can serve as a measure of the action of mutagens, carcinogens, antibiotics, etc.

Morgan's laws of inheritance and the principles of heredity arising from them. The works of T. Morgan played a huge role in the creation and development of genetics. He is the author of the chromosome theory of heredity. They discovered the laws of inheritance: inheritance of sex-linked traits, linked inheritance.

From these laws follows the following principles of heredity:

1. A factor-gene is a specific locus of a chromosome.

2. Gene alleles are located in identical loci of homologous chromosomes.

3. Genes are located linearly on the chromosome.

4. Crossing over is a regular process of gene exchange between homologous chromosomes.

Mobile elements of the genome. In 1948, the American researcher McClintock discovered genes in maize that move from one part of the chromosome to another and called the phenomenon transposition, and the genes themselves control elements (CE). 1.These items can be moved from one site to another; 2. their integration into a given region affects the activity of genes located nearby; 3. loss of CE at a given locus transforms a previously mutable locus into a stable one; 4. In sites where ECs are present, deletions, translocations, transpositions, inversions, as well as chromosome breaks can occur. In 1983, the Nobel Prize was awarded to Barbara McClintock for the discovery of mobile genetic elements.

The presence of transposable elements in genomes has a variety of consequences:

1. Movement and introduction of mobile elements into genes can cause mutations;

2. Change in the state of gene activity;

3. Formation of chromosomal rearrangements;

4. Formation of telomeres.

5. Participation in horizontal gene transfer;

6. Transposons based on the P-element are used for transformation in eukaryotes, gene cloning, search for enhancers, etc.

There are three types of mobile elements in prokaryotes - IS elements (insertions), transposons, and some bacteriophages. IS elements are inserted into any DNA region, often causing mutations, destroying coding or regulatory sequences, and affecting the expression of neighboring genes. The bacteriophage can cause mutations as a result of insertion.

§ 5. T. G. Morgan and his chromosome theory

Thomas Gent Morgan was born in 1866 in Kentucky (USA). After graduating from the university at twenty, Morgan was awarded the title of Doctor of Science at twenty-four, and at twenty-five he became a professor.

Since 1890, Morgan has been engaged in experimental embryology. In the first decade of the 20th century, he was fond of questions of heredity.

It sounds paradoxical, but at the beginning of his activity Morgan was an ardent opponent of Mendel's teachings and was going to refute his laws on animal objects - rabbits. However, the Columbia University trustees found the experience too costly. So Morgan began his research on a cheaper object - the Drosophila fruit fly, and then not only did not come to the denial of Mendel's laws, but also became a worthy successor to his teachings.

A researcher in experiments with Drosophila creates chromosome theory of heredity- the largest discovery, occupying, by expression N. K. Koltsova, "the same place in biology as the molecular theory in chemistry and the theory of atomic structures in physics."

In 1909-1911. Morgan and his equally illustrious students A. Sturtevant, G. Moeller, C. Bridges showed that Mendel's third law requires significant additions: hereditary inclinations are not always inherited independently; sometimes they are transmitted in whole groups - linked to each other. Such groups located on the corresponding chromosome can move to another homologous chromosome during conjugation of chromosomes during meiosis (prophase I).

The full chromosome theory was formulated T. G. Morgan in the period from 1911 to 1926. With his appearance and further development this theory is indebted not only to Morgan and his school, but also to the work of a significant number of scientists, both foreign and domestic, among which, first of all, we should mention N. K. Koltsova and A. S. Serebrovsky (1872-1940).

According to the chromosome theory, transmission of hereditary information is associated with chromosomes, in which linearly, at a certain locus (from lat. locus- place), genes lie. Since the chromosomes are paired, each gene on one chromosome corresponds to a paired gene on the other chromosome (homolog) lying in the same locus. These genes can be the same (in homozygotes) or different (in heterozygotes). Various forms of genes that arise by mutation from the original are called alleles, or allelomorphs(from Greek allo - different, morph - form). Alleles affect the manifestation of a trait in different ways. If a gene exists in more than two allelic states, then such alleles in populations* form a series of so-called multiple alleles. Each individual in a population can contain any two (but no more) alleles in its genotype, and each gamete can contain only one allele, respectively. At the same time, individuals with any alleles of this series can be in the population. Hemoglobin alleles are an example of multiple alleles (see Chapter I, § 5).

* (A population (from Latin popularus - population) is a group of individuals of the same species, united by mutual crossing, to some extent isolated from other groups of individuals of this species.)

The degree of dominance in a series of alleles can increase from the extreme recessive gene to the extreme dominant. Many examples of this type can be cited. So, in rabbits, the recessive gene series multiple alleles is the c gene that determines the development of albinism*. The c h gene of Himalayan (ermine) coloration (pink eyes, white body, dark tips of the nose, ears, tail and limbs) will be dominant in relation to this gene; over this gene, as well as over the c gene, the gene of light gray color (chinchilla) c ch dominates. An even more dominant stage is the agouti gene - c a (dominates over genes c, c h and c ch). The most dominant of the entire series, the black color gene C dominates over all the "lower steps of alleles" - genes c, c h, c ch, c a.

* (Lack of pigment (see chapter VII, § 5).)

Dominance, like the recessiveness of alleles, is not an absolute, but their relative property. The degree of dominance and recessiveness can be different. The same trait can be inherited in a dominant or recessive manner.

So, for example, the fold above the inner corner of the eye (epicanthus) is dominantly inherited in Mongoloids, and recessively in Negroids (Bushmen, Hottentots).

As a rule, newly emerging alleles are recessive, on the contrary, alleles of old plant varieties or animal breeds (even more wild species) are dominant.

Each pair of chromosomes is characterized by a certain set of genes that make up the linkage group. That is why groups of different traits are sometimes inherited together with each other.

Since the somatic cells of Drosophila contain four pairs of chromosomes (2n = 8), and the sex cells contain half as many (1n = 4), the fruit fly has four groups clutch; similarly, in humans, the number of linkage groups is equal to the number of chromosomes of the haploid set (23).

For a number of organisms (Drosophila, corn) and some human chromosomes *, chromosomal or genetic maps have been compiled, which are a schematic arrangement of genes in chromosomes.

* (By now, to establish the exact localization of human genes (if we take into account total number genes) succeeded only in isolated and relatively rare cases, for example, for traits linked to sex chromosomes.)

As an example, let us give a chromosome map of a part of the Drosophila X chromosome (Fig. 24). With greater or lesser accuracy, this map reflects the sequence of genes and the distance between them. It was possible to determine the distance between genes using genetic and cytological analyzes of crossing over, which occurs during the conjugation of homologous chromosomes during the zygonema of prophase I of meiosis (see Chapter II, § 7).

The movement of genes from one chromosome to another occurs with a certain frequency, which is inversely proportional to the distance between genes: the shorter the distance, the higher crossover percentage(the unit of distance between genes is named after Morgan morganida and is equal to the minimum distance in the chromosome that can be measured by crossing over). Crossover is shown in Fig. 25.

At present, the close linkage of some gene loci is known, and the percentage of crossover has been calculated for them. Linked genes determine, for example, the expression Rh factor and genes of the MN-system of blood (on the inheritance of blood properties, see Chapter VII, § 3). In some families, it was possible to trace the linkage of the Rh factor with ovalocytosis(the presence of approximately 80-90% of oval-shaped erythrocytes - the anomaly proceeds, as a rule, without clinical manifestations), which give about 3% crossover. Up to 9% of crossover is observed between the genes that control the manifestations of ABO blood groups and the Lu factor. It is known that the gene that affects the anomaly of the structure of the nails and knee is also linked to the loci of the ABO system; the percentage of crossover between them is about 10. The linkage groups (and, consequently, the chromosome maps) of the human X and Y chromosomes are much better studied (see Chapter VII, § 6). It is known, for example, that the genes that determine the development of color blindness(color blindness) and hemophilia(bleeding); the percentage of overlap between them is 10.

The correctness of Morgan's hypothesis was confirmed at the beginning of the century by Kurt Stern (cytological studies) and Morgan's collaborators Theophilus Painter (cytologist) and Calvin Bridges (geneticist) on the giant chromosomes of the salivary glands of Drosophila larvae (similar to the giant chromosomes of other Diptera). On fig. 26 shows part of a giant chromosome salivary gland Chironomus (bloodworm) larvae.

When studying giant chromosomes with a conventional light microscope, the transverse striation is clearly visible, formed by the alternation of light and darker stripes of disks - chromomeres; they are formed by highly spiralized, densely adjacent areas.

The formation of such giant chromosomes is called polythenia, i.e., the reduplication of chromosomes without increasing their number. At the same time, the reduplicated chromatids remain side by side, tightly adjoining each other.

If a chromosome consisting of a pair of chromatids doubles consecutively nine times, then the number of strands (chromonemes) in such a polytene chromosome will be 1024. Due to the partial despiralization of chromonemes, the length of such a chromosome increases compared to the usual one by 150-200 times.

In 1925, Sturtevant showed the presence unequal crossover: in one of the homologous chromosomes there may be two identical loci, in which, for example, genes that affect the shape of the Drosophila eye - Bar are located, and in the other - not a single locus. This is how flies with a pronounced sign of narrow striped eyes (gene ultra bar)(see fig. 31).

In addition to cytological evidence of the correctness of the chromosome theory, genetic experiments were carried out - crossing different races Drosophila. So, among the many linked genes in the fruit fly, there are two recessive genes: the gene for black body color ( black) and the gene for rudimentary wings ( vestigial).

Let's call them genes a and b. They correspond to two dominant alleles: the gene for the gray body and normally developed wings (A and B). When crossing purebred flies aabb and AABB, the entire first generation of hybrids will have the genotype AaBb. Theoretically speaking, the following results should be expected in the second generation (F 2).

However, in a small but constant percentage of cases, unusual offspring from unusual gametes were encountered. About 18% of such gametes were observed in each crossing (9% Ab and 9% aB).

The occurrence of such exceptions is well explained by the crossover process. Thus, and genetic research made it possible to establish that the violation of adhesion - crossing over, leading to an increase in shape variability, is statistically constant.

In conclusion, we note that whole line provisions of classical genetics today has undergone a number of changes.

We have repeatedly used the terms "dominant" and "recessive" genes (alleles) and traits. However, recent studies have shown that so-called recessive genes may in fact not be recessive at all. It is more correct to say that recessive genes give a very weak visible or invisible manifestation in the phenotype. But in the latter case, recessive alleles, outwardly invisible in the phenotype, can be detected using special biochemical techniques. In addition, the same gene under certain environmental conditions can behave as dominant, under others - as recessive.

Since the development of all organisms occurs depending on and under the influence of the external environment, the manifestation of the genotype in a certain phenotype is also influenced by environmental factors (temperature, food, humidity and gas composition atmosphere, its pressure, the presence of forms pathogenic for a given organism, the chemical composition of water, soil, etc., and for a person, and phenomena of a social order). The phenotype never shows all the genotypic possibilities. Therefore, under different conditions, the phenotypic manifestations of similar genotypes can differ greatly from each other. Thus, both the genotype and the environment are involved (to a greater or lesser extent) in the manifestation of a trait.

Development natural sciences, in particular cytology, and the advent of more powerful microscopes contributed to the study of genetics. Many scientists have been dealing with inheritance issues since the end of the 19th century. At the beginning of the twentieth century, Thomas Morgan, based on the data of researchers, formulated the main provisions of the chromosome theory of heredity.

Story

Thomas Morgan, an American biologist and Nobel laureate, is considered the author of the chromosome theory. It was he who studied and described the mechanism of linked inheritance, and also formulated the main provisions of the theory of chromosomal inheritance. However, Morgan relied on the work of his predecessors - biologists, geneticists, physiologists.

Rice. 1. Thomas Morgan.

A brief history of the formation of Morgan's theory is described in the table.

Year	Scientist	What did you do
	Ivan Chistyakov	Observed the distribution of genetic material between the nuclei of a plant cell
	Oscar Hertwig	Observed fusion of gametes in echinoderms. Concluded that the nucleus carries hereditary information
	Edward Strasburger	Observed nuclear fission in plants. Compare plant and animal cells. He concluded that division in all cells occurs in the same way. Later he introduced many terms of genetics (gamete, meiosis, haploid and diploid set of chromosomes, polyploidy)
	Edward van Beneden	observed meiosis. Revealed that part of hereditary information comes from the father, part - from the mother
	Heinrich Waldeyer	Introduced the term "chromosome". Before him, the terms "chromatin segment" and "chromatin element" were used.
	Theodore Boveri and William Setton	Independently of each other, the relationship of hereditary factors according to Mendel and chromosomes was revealed. These factors were later called genes. Concluded that genes are located on chromosomes
		Published the results of many years of work. Together with his colleagues and students - Calvin Bridges, Alfred Sturtevant, Hermann Möller - he formulated the theory of chromosomal inheritance. Since 1909, experiments have been carried out with fruit Drosophila and revealed the mechanisms of linked inheritance and the way they are violated - crossing over.

In 1933, Thomas Morgan was awarded the Nobel Prize for his contributions to physiology and medicine. The decision for the award was his work on the role of chromosomes in the processes of inheritance.

Regulations

Many researchers independently came to the same conclusions. By the first decade of the twentieth century, the role of chromosomes in inheritance was known, the term “gene” was introduced, sex chromosomes and ways of transmitting hereditary information were identified. The landmark work was a study led by Morgan. Thanks to the observations of the generations of fruit Drosophila and based on the accumulated knowledge, the main provisions of Morgan's chromosome theory of heredity:

• the genes responsible for the inheritance of traits are located on the chromosomes;
• genes are arranged linearly, each gene has its own place in the chromosome - a locus;
• the set of genes on each chromosome is unique;
• groups of genes located close to each other are inherited linked;
• the number of linked genes is equal to the haploid set of chromosomes and is constant for each species (a person has 23 pairs of chromosomes, therefore, 23 pairs of linked genes);
• chromosome cohesion is broken during crossing over (crossover) - the process of exchanging parts of chromosomes in prophase I of meiosis;
• the farther apart the linked groups of genes are on the chromosome, the greater the likelihood of crossing over.

Rice. 2. Linked inheritance.

Morgan's experiments showed that genes located on the same chromosome are inherited linked, falling into one gamete, i.e. two traits are always inherited together. This phenomenon has been called Morgan's law.

Rice. 3. Crossing over.

On the turn of XIX and XX centuries, the main stages of cell division were studied. The lifetime of a cell from its formation to division is cell cycle. The cell cycle is divided into stages, the brightest of which in morphological terms is mitosis or actual cell division. The period between mitoses is called interphase. The key role in mitosis belongs to chromosomes- such structures in the nuclei of cells that are clearly visible during division under light microscopy and the use of specific staining methods. The staining substance of chromosomes is called chromatin. The existence of chromosomes was first shown by Fleming in 1882. The term chromosome was first introduced by Waldeer in 1888 (Greek: chroma - color; soma - body).

The set of chromosomes in one cell is called karyotype. The number and morphology of chromosomes refer to specific features. Different kinds organisms differ in karyotype, while such differences are not observed within the same species, and karyotype anomalies are most often associated with severe pathological conditions. Each chromosome has an important functional region called centromere. The centromere divides the chromosome into two arms: a short (p) and long (q) . Chromosomes are divided into groups depending on their length and location of the centromere. In higher somatic cells, each chromosome is represented by two copies, that is diploid set. And only in germ cells is a single or haploid set chromosomes. This is ensured by a special form of germ cell division - meiosis.

The first extensive studies on the structure and morphology of chromosomes in our country were carried out on plant objects in the 20s of the last century by the outstanding cytologist and embryologist S. G. Navashin and his talented students - M. S. Navashin, G. A. Levitsky , L. N. Delaunay. In 1924, G. A. Levitsky published the world's first manual on cytogenetics: "Material Foundations of Heredity", in which, in particular, he introduced the concept of a karyotype in the sense in which this term is used today.

Let us consider in more detail the main stages of the cell cycle - fig. 5, stages of mitosis - fig. 6 and meiosis - fig. 7.

Figure 5. Cell cycle

The cell that has finished dividing is in the G 0 stage. The longest stage of interphase is the period of relative rest of the cell - G 1 , its duration can vary significantly. Approximately in the middle of the G 1 stage, there is a checkpoint, upon reaching which the cell inevitably enters into division. After G 1, a very important synthetic stage S begins, during which each chromosome is duplicated to form two chromatids connected to each other by a single centromere. This is followed by preparation for mitosis - stage G 2 and mitosis itself - stage M.

Figure 6. Mitosis

Mitosis, in turn, is also divided into stages. On the stage prophase there is a disappearance of the nuclear membrane, condensation or compaction of chromosomes due to their spiralization, migration of centrioles to opposite poles, leading to polarization of the cell, and the formation fission spindle made up of microtubules. Strands of microtubules stretch from one pole to the other and the centromeres of chromosomes are attached to them. During the period metaphase centromeres are located along the equator of the cell perpendicular to the spindle axis. It is during this period that the chromosomes are especially clearly visible, since they are in the most compact state. On the stage anaphase centromere separation occurs, chromatids turn into independent chromosomes and, carried away by centromeres, begin to move to opposite poles of the cell along the fission spindle threads. At the final stage - telophase- Despiralization of chromosomes occurs, the spindle of division disappears, the nuclear membrane forms and the cytoplasm separates. At the stage of interphase, under conventional light microscopy, the chromosomes are not visible as separate structures; only chromatin grains, randomly distributed over the nucleus, are stained.

Figure 7. Meiosis

Meiosis occurs only during the formation of germ cells, and it involves two cell divisions: meiosisI or reduction division and meiosis II. During prophase I of meiosis, homologous chromosomes conjugate (fuse) with each other along their entire length, forming bivalent. At this time, an exchange of sites between non-sister chromatids can occur - crossing over or homologous recombination (Fig. 8.)

Figure 8. Crossover

At the recombination point, a cruciform structure visible in a light microscope is formed - chiasma. Exchange occurs only between two of the four chromatids. Chiasmata are formed randomly, and their number, on average, depends on the length of the chromosome: the longer the chromosome, the more chiasmata. At the metaphase stage, the bivalents line up in the equatorial plane, while the centromeres are randomly oriented relative to the poles of the cell. At the anaphase stage, homologous chromosomes separate from each other and begin to move towards opposite poles. In this case, the splitting of the centromere does not occur, and the sister chromatids are connected. However, they may no longer be identical to each other due to the crossing over that has occurred. Thus, during meiosis I, two haploid cells are formed from one diploid cell. The interval between the first and second divisions of meiosis is called interkinesis. It can be quite long, while the chromosomes are decompacted and look the same as in interphase. It is important to emphasize that chromatid doubling does not occur at this stage.

In the prophase of meiosis II, the spindle of division is restored, the chromosomes are located in the equatorial plane. In anaphase II, the centromere splits, and the chromosomes move to opposite poles. Thus, for one act of doubling of chromosomes, there are two successive cycles of cell division. After completion of telophase II, the diploid parent cell divides into four haploid germ cells, and the resulting gametes are not identical to each other - fragments of the maternal and paternal chromosomes are in them in various combinations.

Investigating the processes of mitosis and meiosis, W. Setton and E. Boveri in 1902 came to the conclusion that the hereditary factors or genes postulated by Mendel are located in the chromosomes, since the behavior of the chromosomes corresponds to the behavior of these hereditary factors. Indeed, Mendel suggested that somatic cells contain two copies of the hereditary factor responsible for the same trait or, as we have already determined, two alleles of the same gene. These alleles can be identical - AA or aa, or different - Ah. But only one of the alleles enters the germ cells - BUT or a. Recall that homologous chromosomes in somatic cells are also contained in two copies, and only one of them gets into the gametes. During fertilization, the double set of chromosomes and gene alleles is restored.

Direct evidence of the localization of genes in chromosomes was obtained later by T. Morgan (1910) and C. Bridges (1916) in experiments on Drosophila. Returning to Mendel's laws, we note that independent combination is valid only for those traits whose genes are in different chromosomes. Parental alleles of genes located on the same chromosome have a high probability of joint entry into the same germ cell. Thus, the idea of ​​a gene appeared as a section of a chromosome or a chromosomal locus, which is responsible for one trait and at the same time is a unit of recombination and mutation leading to a change in the phenotype.

The chromosomes of higher organisms are made up of euchromatin and heterochromatin, which maintains its compact position throughout the entire cell cycle. It is heterochromatin that is visible in the interphase nuclei in the form of stained granules. A large amount of heterochromatin is localized in the region of the centromere and at the ends of chromosomes, which are called telomeres. Although the functions of heterochromatin are not completely understood, it is assumed that it plays an important role in maintaining the structural integrity of chromosomes, in their proper segregation during cell division, and also in the regulation of gene function. Euchromatin on the preparations has a lighter color, and, apparently, in these areas is localized most of genes. Chromosomal rearrangements often occur in the region of heterochromatin. A great role in the study of the structure and functions of heterochromatic and euchromatic regions of chromosomes belongs to our outstanding compatriot Alexandra Alekseevna Prokofieva-Belgovskaya. For the first time detailed morphological description ten largest human chromosomes and various groups smaller chromosomes is presented in the works of the leading domestic cytologists M. S. Navashin and A. G. Andres in the mid-30s of the last century.

In 1956, Thio and Levi, using colchicine treatment of histological preparations, determined that humans have 46 chromosomes, consisting of 23 different pairs. Colchicine delays cell division at the metaphase stage, when the chromosomes are most condensed and therefore convenient for recognition. On fig. 9 shows a scheme for differential staining of human chromosomes.

Figure 9. Scheme of differential staining of human chromosomes

In females, both chromosomes of each pair are completely homologous to each other in shape and staining pattern. In men, this homology is preserved only for 22 pairs of chromosomes, which are called autosomes. The remaining pair in men consists of two different sex chromosomes -XandY. In females, the sex chromosomes are represented by two homologous X chromosomes. Thus, the normal karyotype of a woman is written as (46, XX), and for men - (46, XY). Only one set of chromosomes enters the germ cells of both men and women. All eggs carry 22 autosomes and an X chromosome, but spermatozoa differ - half of them have the same set of chromosomes as the eggs, and the other half has a Y chromosome instead of the X chromosome. During fertilization, the double set of chromosomes is restored. In this case, who will be born - a girl or a boy - depends on which spermatozoon took part in fertilization, the one that carries the X chromosome or the one that carries the Y chromosome. As a rule, this is a random process, so girls and boys are born with approximately equal probability.

At the initial stages of the analysis of the human karyotype, individual identification could be carried out only in relation to the first three largest chromosomes. The remaining chromosomes were divided into groups depending on their size, location of the centromere, and the presence of satellites or satellites- small compact fragments separated from the chromosome by thin constrictions. On fig. 10 shows the types of chromosomes: acrocentric, metacentrics and submetacentrics with the localization of the centromere, respectively, at the end of the chromosome, in the middle and in an intermediate position.

Figure 10. Chromosome types

In accordance with the accepted classification, 7 groups of chromosomes are distinguished in humans: A, B, C, D, E, F and G or 1, 2, 3, 4, 5, 6 and 7. For better identification of chromosomes, they are arranged into groups or karyogram. On fig. 11 shows a female karyotype and its karyogram.

Figure 11. Female karyotype and its karyogram

In the early 70s of the XX century, methods for differential staining of chromosomes using the Giemsa stain (G-, R-, C-, Q-methods) were developed. At the same time, a characteristic transverse striation is revealed on the chromosomes, the so-called disks or bands, the location of which is specific to each pair of chromosomes. Methods of differential staining of chromosomes make it possible to identify not only each chromosome, but also individual regions of chromosomes, sequentially numbered from centromere to telomere, as well as segments within regions. For example, the record Xp21.2 means the short arm of the X chromosome, region 21, segment 2. This record is very convenient for determining whether genes or other elements of the genome belong to certain chromosomal loci. In particular, the Duchenne myodystrophy gene is localized in the Xp21.2 region - DMD. Thus, methodological foundations were created for studying the features of the karyotype in different types organisms, determining its individual variability and anomalies under certain pathological conditions. The branch of genetics that deals with the study of chromosomes and their anomalies is called cytogenetics. The first cytogenetic maps of human chromosomes were compiled by C. B. Bridges and Sturtevant.

In the first half of the 20th century, the chromosome theory of heredity received significant development. It has been shown that genes are arranged linearly on chromosomes. The genes on one chromosome form clutch group and are inherited together. New combinations of alleles of genes of one chromosome can be formed due to crossing over, and the probability of this event increases with increasing distance between genes. Units of measurement of genetic distance were introduced - centimorgans or morganides, named after the founder of the chromosome theory of heredity - Thomas Morgan. Two genes on the same chromosome are considered to be at a distance of 1 centimorgan (cM) if the probability of crossing over between them during meiosis is 1%. Of course, centimorgans are not absolute units for measuring distance in chromosomes. They directly depend on crossing over, which can occur at different frequencies in different parts of the chromosomes. In particular, in the region of heterochromatin, crossing over is less intense.

Note that the above-described character of the division of somatic and germ cells - mitosis and meiosis, is valid for eukaryote, that is, such organisms in the cells of which there are nuclei. Bacteria that belong to the class prokaryotes, there are no nuclei, but one chromosome is present in the cell and, as a rule, it has a ring shape. Along with the chromosome, prokaryotic cells in a large number of copies can contain much smaller ring structures called plasmids.

In 1961, M. Lyon put forward a hypothesis that in females, one of the X chromosomes is inactivated. And in different cells X chromosomes of both paternal and maternal origin can be inactivated. In the analysis of the female karyotype, the inactivated X chromosome appears as a compact, well-stained, rounded chromatin structure located close to the nuclear membrane. it Barr body or sex heterochromatin. His identification is the most in a simple way cytogenetic diagnosis of sex. Recall that in the Y chromosome there are practically no homologues of the X chromosome genes, however, inactivation of one of the X chromosomes leads to the fact that the dose of most genes localized in the sex chromosomes in men and women is the same, that is, inactivation of the X chromosome in women is one of the mechanisms for compensating the dose of genes. The process of X chromosome inactivation is called lyonization and he wears random character. Therefore, in the body of women, the ratio of cells with an inactivated X chromosome of paternal or maternal origin will be approximately the same. Thus, women heterozygous for a mutation in a gene located on the X chromosome have a mosaic phenotype - one part of the cells contains a normal allele, and the other contains a mutant one.