X is a linked feature. X-linked inheritance

An X-linked recessive disease (or symptom) always manifests itself in men with the corresponding gene, and in women only in cases of

a mozygotic state (which is extremely rare).

An example of an X-linked recessive disease is hemophilia A, characterized by impaired blood clotting due to a deficiency of factor VIII - antihemophilic globulin A. The pedigree of a patient with hemophilia is shown in Fig. IX.11. Clinically, the disease is manifested by frequent prolonged bleeding, even with a minor wound, hemorrhages in organs and tissues. The incidence of the disease is 1 in 10,000 newborn boys. Using the above notation, it is possible to determine all possible genotypes in the offspring of a sick man and a healthy woman (Fig. IX. 12).

According to the scheme, all children will be phenotypically healthy, but genotypically all daughters are carriers of the hemophilia gene. If a woman, a carrier of the hemophilia gene, marries a healthy man, the following variants of the genotypes of the offspring are possible (Fig. IX. 13).

Daughters in 50% of cases will be carriers of the pathological gene, and for sons there is a 50% risk of being sick with hemophilia.

Thus, the main features of X-linked recessive inheritance are as follows:

1) the disease occurs mainly in males;

2) the trait (disease) is transmitted from a sick father through his phenotypically healthy daughters to half of his grandchildren;

3) the disease is never transmitted from father to son;

4) carriers sometimes show subclinical signs of pathology.

More on the topic Recessive X-linked type of inheritance of the disease:

1. 1. Ideas about heredity, variability, relationship, norm and deviation in the pre-scientific period.

In X-linked diseases, the abnormal gene is located on the X chromosome. X-linked diseases are significantly different from autosomal diseases.

Because females inherit two copies of the X chromosome, they can be heterozygous and sometimes homozygous for any allele at a particular locus. Therefore, in women, X-linked genes appear in the same way as autosomal genes. As a result of the inactivation of the X chromosome (this process is random and occurs at the early stages of embryogenesis in females), only one X chromosome is active in each cell of the body. This means that in women heterozygous for the mutant X-linked allele, the product of the normal gene is produced in an amount of 50% of the normal one, which also happens in heterozygotes in autosomal recessive conditions. Usually, this amount of the gene product is sufficient for normal phenotypic manifestations. Since a man inherits only one X chromosome, he is hemizygous for all genes on the X chromosome, and all genes are expressed. In the case of hereditary transmission of the X-linked mutant gene, phenotypic manifestations of the disease develop, since the Y-chromosome does not contain normal alleles that can compensate for the function of the mutant gene.

X-linked inheritance of the recessive type

For X-linked inheritance of the recessive type, the following features are characteristic:

• the incidence of the disease is significantly higher in men;
• in heterozygous female carriers, phenotypic manifestations of the disease are usually absent;
• the gene is passed from a sick man to all of his daughters, and the son of any of his daughters has a 50% risk of inheriting the gene;
• the mutant gene is not passed from father to son;
• the mutant gene can be transmitted through a series of female carriers, then the connection between all sick men is established through female carriers;
• a significant proportion of sporadic cases of the disease are the result of a new mutation.

There are situations in which the development of phenotypic manifestations of X-linked inheritance in females is possible. If both parents are carriers of the X-linked recessive gene, the girl can get the mutant gene in a homozygous state. But due to the fact that X-linked inheritance of the recessive type is rare, this situation is unlikely (with the exception of closely related marriages). Girls with Turner syndrome, which is characterized by a set of chromosomes 45, X, are hemizygotes for all genes contained on the X chromosome; in this case, all genes contained in all loci of the X chromosome are expressed, as in males. Finally, since the inactivation of the X chromosome is random, in the fetus it obeys the law of normal distribution. Therefore, in a small part of women, almost complete inactivation of one X chromosome is possible. This pathological (asymmetric) character of X-chromosome inactivation is often observed in women with phenotypic manifestations of X-linked recessive diseases.

Hemophilia A: a typical example of X-linked inheritance of the recessive type. Hemophilia A (classic hemophilia) is characterized by a deficiency of coagulation factor VIII, which leads to prolonged bleeding after trauma, tooth loss, impossibility of surgery, recurrent bleeding after stopping primary bleeding and delayed bleeding. The onset of clinical manifestations and the frequency of bleeding episodes depend on the coagulating activity of factor VIII; there are severe and mild forms of the disease. Severe cases are usually diagnosed in infancy; mild cases may go unrecognized until adolescence or adulthood. As a result of asymmetric inactivation of the X chromosome, 10% of female carriers may have mild bleeding.

The diagnosis of hemophilia A is established by determining the low coagulating activity of factor VIII, provided the level of von Willebrand factor is normal. Molecular genetic research identifies mutations responsible for the development of the disease in about 90% of patients. It is not necessary to carry out this research in all cases, but it is quite affordable. Molecular genetic testing is used in genetic counseling of at-risk family members and sometimes to diagnose mild cases.

Hemophilia A has an X-linked inheritance of the recessive type. The risk of developing the disease in siblings of a proband depends on whether the mother is a carrier of the mutant gene. The risk of passing the mutant B8 gene from a female carrier is 50% with every pregnancy. If the mutation is passed on to sons, they develop phenotypic manifestations of the disease; daughters to whom the mutation is passed become carriers of the mutation. Sick men pass the mutation on to all daughters, not sons.

X-linked dominant inheritance

X-linked diseases are considered dominant if the disease occurs regularly in heterozygous female carriers. Characteristic features of the X-linked dominant:

• the disease is phenotypically manifested in all daughters and does not develop in the sons of a sick man;
• the sons and daughters of sick women have a 50% risk of inheriting the disease;
• rare X-linked dominant diseases are more common in women, but the disease in women is characterized by milder (albeit variable) phenotypic manifestations.

Only a few diseases with X-linked dominant inheritance are known. One of them is hypophosphatemic rickets. Although this disease affects both sexes, the disease is more severe in men. Some rare X-linked diseases develop almost exclusively in women, since a hemizygous state for this gene in male fetuses leads to death. These include pigment incontinence, which manifests itself in the form of damage to the skin, hair, teeth and nails. Skin lesions go through characteristic stages, starting with the formation of blisters on the skin in infancy, then warty rashes appear (and persist for several months), eventually giving way to areas of hyper- and hypopigmentation. Alopecia, hypodontia, abnormal shape of teeth and degenerative changes in nails are observed. Some patients have retinal vascular abnormalities that predispose to retinal detachment at an early age, psychomotor retardation, or mental retardation. Diagnosis of pigment incontinence disease is clinical and, in some cases, is confirmed by skin biopsy. In affected women, the risk of passing the IKBKG mutant allele to offspring is 50%. The affected male fetus is not viable. The estimated live birth rate is 33% of unaffected girls, 33% of affected girls and 33% of healthy boys.

Genes localized on the sex chromosomes are called sex-linked genes. Sex-linked genes can be located on both the X chromosome and the Y chromosome. However, in clinical genetics, X-linked diseases are of practical importance, i.e. those in which pathological genes are located on the X chromosome.

The distribution of the X-linked trait in the offspring depends on the distribution of the X-chromosome carrying the abnormal gene. Since women have two X-chromosomes, and men have one, the following variants of genotypes are possible: in men - HOW; HAU, in women - HAHA; HAH; HaHa; (XA is the dominant gene located on the X chromosome, Xa is the recessive gene located on the X chromosome).

Thus, in women, the following are possible: genotype homozygous for the dominant allele, heterozygous genotype, and genotype homozygous for the recessive allele. In men, only a hemizygous genotype is possible, because the allele located on the X chromosome in a man does not have a pair on the Y chromosome.

X - linked, recessive inheritance

X - linked recessive diseases are manifested in men with the corresponding gene, and in women only in the case of a homozygous state (which is extremely rare), more often in consanguineous marriages.

Using the above notation, it is possible to determine all possible genotypes of children in the offspring of a sick man and a healthy woman:

Parents HOW x HAHA

Gametes Ha woo ha ha

Children HAH; HAH; HOW; HOW

According to the scheme, all children will be phenotypically healthy, but genotypically all daughters are heterozygous carriers. If a carrier woman marries a healthy man, the following options are possible in the offspring:

Parents HOW x HAH

Gametes HA U HA Ha

Children HAHA; HAH; HOW; HOW

Daughters in 50% of cases will be carriers of the pathological gene, and for sons there is a 50% risk of being sick.

Thus, the main criteria for diseases with an X-linked type of inheritance are as follows:

• 1. The disease occurs mainly in males. Sick homozygous women with X-linked recessive diseases are an exception that occurs when a sick man marries a carrier of the gene for this disease.
• 2. The disease is transmitted from a sick father through his phenotypically healthy daughters to half of his male grandchildren (inheritance by the "move of a chess knight").
• 3. The disease is never transmitted from father to son.
• 4. Carriers may show subclinical signs of disease.
• 5. The degree of risk for the sons of a woman who is a reliable carrier of the disease is 50%.
• 6. Half of the daughters of women who are carriers of the disease will also be carriers.

All phenotypically healthy daughters of the affected father are obligate heterozygous carriers.

By itself, the transmission of a trait from affected grandfathers through healthy mothers to affected grandchildren cannot yet serve as evidence of the localization of the gene on the X chromosome. A similar type of transmission is possible in the case of an autosomal gene, the manifestation of which is limited to the male sex. Crucial is the fact that all the sons of the affected men are healthy. However, this criterion cannot be used if the disease is so severe that patients do not leave offspring.

In contrast to X-linked recessive inheritance, diseases with X-linked dominant inheritance are twice as common in women as in men. Affected individuals usually have normal fertility. The main characteristic of X-linked dominant inheritance is that sick men pass the gene (or disease) on to all their daughters and none of their sons. A sick woman transmits an X-linked dominant gene to half of her children, regardless of gender, as in the autosomal dominant mode of inheritance. Thus, only children of affected fathers make it possible to distinguish between X-linked dominant and autosomal dominant inheritance. For all traits with an established X-linked dominant mode of inheritance, it was shown that, on average, men were affected more severely than women. This is natural, since in heterozygous women, partial compensation can be determined by the presence of a normal allele in the other X chromosome. This fact became completely explainable after the discovery of the phenomenon of accidental inactivation of one of the K-chromosomes in women (lionization). X-linked dominant inheritance occurs when hemizygote males are lethal.

As noted, X-linked diseases are usually less severe in women than in men. In some cases, the defeat of male zygotes is so severe that they die in utero. Then in the pedigrees among the affected there should be only women, and among their affected children only daughters, and in a ratio of 1: 1: 1 to healthy daughters and sons. In addition, male hemizygotes that do not die at a very early stage of pregnancy should be found in spontaneous abortions or among stillborn boys. Lenz (1961) was the first to show that this type of inheritance exists in humans for a disease known as pigment incontinence (Bloch-Sulzberger syndrome). It is assumed that the lethality of male fetuses occurs with mouth-face-digital syndrome (multiple hyperplastic frenulum of the tongue, cleft lip and palate, hypoplasia of the wings of the nose, asymmetric shortening of the fingers), Rett-Goltz syndrome and other diseases.

An example of an X-linked recessive disease is hemophilia - A - incoagulability of blood due to a deficiency of the eighth factor of the blood coagulation system. Clinical signs include frequent and prolonged bleeding, even from a small wound, hemorrhage into internal organs and joints. The incidence of the disease is 1 in 10,000 newborn boys. As a rule, men suffer from hemophilia, and the mothers of the latter are healthy women, as a rule, carriers of the recessive hemophilia gene. If hemophilic men marry healthy women, then their sons will inherit the Y chromosome, which is free of this gene. They are healthy and do not carry the hemophilia gene. Daughters of hemophilic men are phenotypically healthy, but all are heterozygous for the hemophilia gene, i.e. carriers of this gene. Their sons, in 50% of cases, will also inherit hemophilia genes and will be sick. 50% of the daughters of such a mother will also be heterozygous. Since boys do not have a second X chromosome, the recessive mutant gene for hemophilia exerts its effect, and children suffer from hemophilia. Girls have two X chromosomes, the dominant (normal) gene is localized on the second X chromosome, so the inherited recessive gene does not show its effect - girls do not get hemophilia. Thus, in this case, 50% of boys will be affected by hemophilia and 50% of girls will be heterozygous carriers of hemophilia.

Women can also suffer from hemophilia. Such cases are described in the literature, but they occur only when girls are born to parents, one of whom is hemophilic (father), the other is a heterozygous carrier (mother). The likelihood of such a marriage is small.

The transfer of the recessive gene that determines hemophilia from heterozygous carriers to their daughters, grandchildren, etc., who become heterozygous carriers and whose sons in 50% of cases suffer from hemophilia, is well traced when familiarizing with the genealogy of some reigning families in Europe. Their ancestry comes from Queen Victoria of England, who was heterozygous for the hemophilia gene. Three great-grandsons of Queen Victoria died of hemophilia - the Spanish Infants Alphonse, Gonzalo - James, who were the sons of Alphonse XIII and Victoria Eugenia of Battenberg. Hemophilic was also the son of the last Russian Tsar Nicholas 11, Alexei, who inherited the hemophilia gene from his mother, Tsarina Alexandra Feodorovna (Alice), and the latter, in turn, received it through her mother from her great-grandmother, Queen Victoria.

Table 2. Identification of carriers in X-linked diseases (according to F. Vogel and A. Motulski, 1989)

Another example of inheritance of genes linked to the X chromosome is inheritance color blindness(color blindness), which, for example, in the United States occurs in 8% of men and 0.5% of women. Inheritance of color blindness is similar to inheritance of hemophilia, because the recessive gene is located on the X chromosome. The father passes the X chromosome to all daughters, but none of the sons, and the mother passes one of her two X chromosomes to all children. In this regard, the sons of the mother of the color blind are also color blind, and regardless of the state of vision of the father. However, if the father has normal vision, then all his daughters inherit normal vision from this marriage, although they will be heterozygous carriers. In the marriage of the latter with men whose eyesight is normal, girls with normal vision will be born, and boys are color-blind and with normal vision in a ratio of 1: 1. A color-blind girl can be born only in a marriage of a color-blind man with a color-blind woman or with a heterozygous carrier.

X-linked dominant inheritance

Among the diseases characterized by X-linked dominant inheritance, one can name vitamin D-resistant rickets (phosphatic diabetes), characterized by skeletal damage and not amenable to vitamin D treatment.

Let us give examples of marriages in diseases with X - linked dominant mode of inheritance.

SICK FATHER

Parents HOW NS Haha

Gametes of parents HA Woo Ha Ha

Descendants HAH; HOW; HAH; Ha Woo

All daughters are healthy carriers, sons are healthy

SICK MOTHER

Parents HOW x HAH

Gametes of parents Ha Woo Ha Ha

Descendants HAH; HaHa; HOW; HOW

The probability of getting sick is 50% for children, regardless of gender.

It is known that over two hundred human genes are localized on the X chromosome. In particular, genes that control hemophilia are localized on the X chromosome. A and V, muscular dystrophy, color blindness, juvenile glaucoma, optic nerve atrophy, retinitis pigmentosa, etc. Over 60 genes in the X chromosome determine mental retardation syndromes. Most of these diseases are inherited in a recessive manner. The dominant type of inheritance in the case of diseases that are determined by genes linked to the X chromosome is more rare. Examples of diseases with mental retardation determined by genes located on the X chromosome are shown in Table 3.

Table 3.X - linked syndromes - mental retardation

As an example of hereditary anomalies controlled by genes localized on the Y-chromosome, syndactyly (membranous fusion of the 2nd and 3rd toes) and hypertrichosis (hairiness) of the edge of the auricle should be mentioned. Since the Y chromosome is found only in males, these genes are passed on to offspring only through the male line.

inheritance gene disease mutation

X-linked recessive inheritance(eng. X-linked recessive inheritance ) is one of the types of sex-linked inheritance. This inheritance is characteristic of traits whose genes are located on the X chromosome and which appear only in a homozygous or hemizygous state. This type of inheritance has a number of congenital hereditary diseases in humans, these diseases are associated with a defect in any of the genes located on the sex X chromosome, and are manifested if there is no other X chromosome with a normal copy of the same gene. In the literature, there is an abbreviation XR to denote X-linked recessive inheritance.

For X-linked recessive diseases, it is typical that men are usually affected, for rare X-linked diseases this is almost always true. All of their phenotypically healthy daughters are heterozygous carriers. Among the sons of heterozygous mothers, the ratio of sick to healthy is 1 to 1.

A special case of X-linked recessive inheritance is criss cross inheritance (eng. criss-cross inheritance, also criss-cross inheritance), as a result of which the signs of fathers appear in daughters, and signs of mothers - in sons. The name of this type of inheritance was given by one of the authors of the chromosomal theory of inheritance, Thomas Hunt Morgan. He first described this type of inheritance for the eye color trait in Drosophila in 1911. Criss-cross inheritance is observed when the mother is homozygous for a recessive trait localized on the X chromosome, and the father has a dominant allele of this gene on a single X chromosome. The identification of this type of inheritance in the analysis of cleavage is one of the proofs of the localization of the corresponding gene on the X chromosome.

Features of inheritance of sex-linked recessive traits in humans

In humans, like all mammals, the male sex is heterogametic (XY), and the female sex is homogametic (XX). This means that males have only one X and one Y chromosome, while females have two X chromosomes. The X chromosomes and Y chromosomes have small homologous regions (pseudoautosomal regions). The inheritance of traits whose genes are located in these regions is similar to the inheritance of autosomal genes and is not discussed in this article.

Traits linked to the X chromosome can be recessive and dominant. Recessive traits do not appear in heterozygous individuals in the presence of a dominant trait. Since males only have one X chromosome, males cannot be heterozygous for those genes on the X chromosome. For this reason, only two states of the X-linked recessive trait are possible in men:

• if there is an allele in a single X chromosome that determines a trait or disorder, a man manifests such a trait or disorder, and all his daughters receive this allele from him along with the X chromosome (sons will receive a Y chromosome);
• if there is no such allele in the only X chromosome, then in a man this trait or disorder does not manifest itself and is not transmitted to offspring.

Since women have two X chromosomes, three conditions are possible for X-linked recessive traits:

• the allele that determines this trait or disorder is absent in both X chromosomes - the trait or disorder does not manifest itself and is not transmitted to the offspring;
• an allele that determines a trait or disorder is present only on one X chromosome - a trait or disorder usually does not manifest itself, and when inherited, about 50% of the offspring receive this allele from it along with the X chromosome (the other 50% of offspring will receive a different X chromosome) ;
• an allele that determines a trait or disorder is present on both X chromosomes - the trait or disorder manifests itself and is transmitted to the offspring in 100% of cases.

Some X-linked recessive disorders can be severe enough to result in fetal death. In this case, there may not be a single known patient among family members and among their ancestors.

Women who have only one copy of the mutation are called carriers. Usually, such a mutation is not expressed in the phenotype, that is, it does not manifest itself in any way. Certain diseases with X-linked recessive inheritance still have some clinical manifestations in female carriers due to the mechanism of dose compensation, due to which one of the X chromosomes is accidentally inactivated in somatic cells, and one X-allele is expressed in some cells of the body, and in others - another.

Certain X-linked recessive human diseases

Common

Common X-linked recessive diseases:

• Hereditary violation of color vision (color blindness). Approximately 8% of men and 0.5% of women suffer from varying degrees of weakness of red-green perception in Northern Europe.
• X-linked ichthyosis. Dry, coarse areas appear on the skin of patients due to excessive accumulation of sulfonated steroids. It occurs in 1 in 2000-6000 men.
• Duchenne muscular dystrophy. A disease accompanied by degeneration of muscle tissue and leading to death at a young age. It occurs in 1 out of 3600 male newborns.
• Hemophilia A (classic hemophilia). The disease associated with deficiency of factor VIII blood clotting occurs in one in 4000-5000 men.
• Hemophilia B. The disease associated with deficiency of factor IX clotting occurs in one in 20,000-25,000 men.
• Becker muscular dystrophy. The disease is similar to Duchenne muscular dystrophy, but the course is somewhat milder. It occurs in 3-6 out of 100,000 male newborns.
• Kabuki syndrome - multiple birth defects (heart defects, growth deficits, hearing loss, urinary tract abnormalities) and mental retardation. Prevalence 1: 32000.
• Androgen insensitivity syndrome (Morris syndrome) - An individual with complete syndrome has a feminine appearance, developed breasts and vagina, despite the 46XY karyotype and undescended testes. The frequency of occurrence is from 1:20 400 to 1: 130,000 newborns with a 46, XY karyotype.

Rare

• Bruton's disease (congenital agammaglobulinemia). Primary humoral immunodeficiency. It occurs among boys with a frequency of 1: 100,000 - 1: 250,000.
• Wiskott-Aldrich syndrome - congenital immunodeficiency and thrombocytopenia. Prevalence: 4 cases per 1,000,000 male newborns.
• Lowe's syndrome (oculocereborenal syndrome) - skeletal anomalies, various renal disorders, glaucoma and cataracts from early childhood. It occurs with a frequency of 1: 500,000 male newborns.
• Allan-Herndon-Dudley syndrome is a rare syndrome that occurs only in men, in which postnatal brain development is impaired. The syndrome is caused by a mutation in the MCT8 gene, which encodes a protein that transports thyroid hormone. First described in 1944.

This brochure provides information on what is X-linked inheritance and how X-linked diseases are inherited.

What are genes and chromosomes?

Our body is made up of millions of cells. Most cells contain a complete set of genes. Man has thousands of genes. Genes can be compared to instructions used to control growth and coherence throughout the body. Genes are responsible for many of the traits in our bodies, such as eye color, blood type, or height.

Figure 1: Genes, Chromosomes and DNA

Genes are located on threadlike structures called chromosomes. Normally, most cells in the body contain 46 chromosomes. Chromosomes are passed on to us from our parents - 23 from mom, and 23 from dad, so we often look like our parents. Thus, we have two sets of 23 chromosomes, or 23 pairs of chromosomes. Since genes are located on chromosomes, we inherit two copies of each gene, one copy from each of the parents. Chromosomes (and hence genes) are made up of a chemical compound called DNA.

Figure 2: 23 pairs of chromosomes distributed by size; chromosome number 1 is the largest. The last two chromosomes are sex chromosomes.

The chromosomes (see Figure 2), numbered 1 through 22, are the same in males and females. These chromosomes are called autosomes. The chromosomes of the 23rd pair are different in women and men, and they are called sex chromosomes. There are 2 variants of sex chromosomes: the X chromosome and the Y chromosome. Normally, women have two X chromosomes (XX), one of them is transmitted from the mother, the other from the father. Normally, males have one X chromosome and one Y chromosome (XY), with the X chromosome passed from the mother and the Y chromosome from the father. So, in Figure 2, the chromosomes of a man are shown, since the last, 23rd, pair is represented by a combination of XY.

Sometimes a change (mutation) occurs in one copy of a gene that disrupts the normal functioning of the gene. Such a mutation can lead to the development of a genetic (hereditary) disease, since the altered gene does not transmit the necessary information to the body. X-linked diseases are caused by changes in the genes of the X chromosome.

What is X-linked inheritance?

The X chromosome contains many of the genes that are very important for the growth and development of the body. The Y chromosome is much smaller in size and contains fewer genes. As you know, women have two X chromosomes (XX), therefore, if one copy of a gene on the X chromosome is changed, then the normal copy on the second X chromosome can compensate for the function of the changed one. In this case, the woman is usually a healthy carrier of an X-linked disease. A carrier is a person who has no signs of the disease, but has an altered copy of the gene. In some cases, women may have moderate manifestations of the disease.

Men have one X and one Y chromosome, so when one copy of a gene on the X chromosome is altered, there is no normal copy of the gene to compensate for the function. This means that such a man will be sick. Diseases that are inherited in the manner described above are called X-linked recessive diseases. Examples of such diseases are hemophilia, Duchenne muscular dystrophy and fragile X syndrome.

X-linked dominant inheritance

Most X-linked diseases are recessive, but in rare cases X-linked diseases are inherited as dominant. This means that if a woman has one altered and one normal copy of the gene, then this will be enough for the disease to manifest. If a man inherits an altered copy of the X chromosome gene, then he will develop a disease, since men have only one X chromosome. In sick women, the probability of having a sick child is 50% (1 in 2), and it is the same for daughters and sons. In a sick man, all daughters will be sick, and all sons will be healthy.

How are X-linked diseases inherited?

If a female carrier has a son, then she can transfer to him either an X chromosome with a normal copy of the gene, or an X chromosome with an altered copy of the gene. Thus, each son has a 50% (1 in 2) chance of inheriting an altered copy of the gene and getting sick. At the same time, there is the same 50% (1 in 2) chance that the son will inherit a normal copy of the gene, in which case he will not have the disease. This probability is the same for every son (Fig. 3).

If a female carrier has a daughter, she will transmit either an X chromosome with a normal copy of the gene, or an X chromosome with an altered copy. Thus, each daughter has a 50% (1 in 2) chance of inheriting an altered copy of the gene, in which case she will be a carrier, like her mother. On the other hand, there is the same 50% (1 in 2) chance that the daughter will inherit a normal copy of the gene, in which case she will be healthy and not be a carrier (Fig. 3).

Figure 3: How X-linked recessive diseases are transmitted from female carriers

Figure 4: How X-linked recessive diseases are transmitted from sick men

If a man with an X-linked disease has a daughter, he will always give her an altered copy of the gene. This is because men only have one X chromosome and they always pass it on to their daughters. Thus, all of his daughters will be carriers (Fig. 4). As a rule, daughters are healthy, but they have a risk of having sick sons.

If a man with an X-linked disease has a son, he will never pass on an altered copy of the gene to him. This is due to the fact that men always pass on the Y chromosome to their sons (if they pass on the X chromosome, they will have a daughter). Thus, all the sons of a man with X-linked disease will be healthy (Fig. 4).

What happens if the patient is the first in the family to have this disease?

Sometimes a child with an X-linked genetic disorder may be the first in the family to have the disorder. This can be explained by the fact that a new mutation (change) in the gene has occurred in the sperm or egg from which this child developed. In this case, none of the child's parents will be a carrier of the disease. These parents are very unlikely to have another child with the same condition. However, a sick child who has an altered gene can pass it on to their children in the future.

Carriage test and prenatal diagnosis (test during pregnancy)

For people with a family history of X-linked recessive hereditary disease, there are several options for testing. Carrier analysis can be performed in women to determine if they are carriers of mutations (changes) in a particular gene on the X chromosome. This information can be helpful when planning your pregnancy. For some X-linked diseases, prenatal diagnosis (that is, diagnosis during pregnancy) is possible to determine if the child has inherited the disease (for more information, see the brochures Chorionic villus sampling and Amniocentesis).

Other family members

If someone in your family has an X-linked disease or is a carrier, you may want to discuss this with other family members. This will provide an opportunity for women in your family, if desired, to undergo an examination (special blood test) to determine whether they are carriers of the disease. This information can also be important for relatives when diagnosing a disease. This can be especially important for those relatives who have or will have children.

Some people may find it difficult to discuss their genetic condition with other family members. They may be afraid to disturb family members. In some families, because of this, people experience difficulties in communication and lose understanding with relatives.

Geneticists are usually experienced in dealing with these kinds of family situations and can help you discuss the problem with other family members.

What is important to remember

• Women who are carriers of an X-linked disease have a 50% chance of passing on an altered copy of the gene to their children. If the son inherits the modified copy from the mother, then he will be sick. If the daughter inherits the modified copy from the mother, then she will be the carrier of the disease, like her mother.
• A man with an X-linked recessive disorder will always pass on an altered copy of the gene to his daughter, and she will be the carrier. However, if it is an X-linked dominant disease, then his daughter will be sick. A man never passes on an altered copy of a gene to his son.
• An altered gene cannot be corrected - it remains altered for life.
• The altered gene is not contagious, for example, its carrier may be a blood donor.
• People often feel guilty about having a genetic disorder in their family. It is important to remember that this is not someone else's fault or the result of someone else's actions.