Hemophilia is a severe hereditary disease characterized by a clotting disorder (coagulation) resulting from the absence of coagulation factors VIII (hemophilia A) or IX (hemophilia B). The main manifestations of hemophilia are hemorrhages in muscles, joints, and internal organs. The mechanism and type of inheritance of hemophilia have been studied in detail. Genes that provoke insufficient production of blood clotting factors are linked to the X chromosome. Pathology is inherited in a recessive manner in the female line. Hereditary pathology occurs exclusively in boys. The sons of a healthy man and a woman carrying a pathological gene are equally likely to be born without or with signs of hemophilia (Lannoy and Hermans, 2020). A man suffering from blood clotting disorders will be able to conceive healthy children with a woman who is not a carrier of the altered gene.
Medicine is aware of isolated cases of detection of hemophilia in women. Their mothers were carriers of the mutated gene, and their fathers suffered from insufficient production of blood clotting factors. The cause of hemophilia in such cases is the combination of recessive and dominant genes. The father’s parents’ chromosomes will look like this; given that the father’s brother is a carrier of hemophilia, the second boy will have XHY0 genes.
The child’s ability to be a carrier of the disease depends on the mother’s genotype. If its set of chromosomes is equivalent to XHXh, then the child’s probability of inheriting the disease will be 25%, similar to the first table data. However, if the mother’s genes are XHXH, then the child’s chance of having hemophilia is zero:
Turner syndrome is a chromosomal disease characterized by either the complete absence of one chromosome or a defect in one of the X chromosomes. Such women’s karyotype is most often represented by 45 X0, or a mosaic variant – 45 X / 46 XX, 45 X / 46 XY. In many patients, one common X chromosome is found in the karyotype. At the same time, the other can be presented with a structural abnormality: isochromosome X (i), ring X chromosome r (X) deletion of the short arm of the X chromosome (Xp-), deletion of the long arm X -chromosome (Xq-) which loses a short arm and consists of two long components of the X chromosome. This syndrome occurs with a frequency of 1: 2000-1: 2500 newborn girls (Gravholt et al., 2019). The X chromosome contains genes that control the development of the gonads, growth, and sexual maturation processes. A violation of their function leads to severe growth retardation, bone anomalies, and multiple defects. Depending on what karyotype the patient has, the syndrome’s manifestations can vary from typical symptoms of the syndrome to their complete absence.
As a rule, the syndrome is not inherited; pathology occurs in the early stages of fetal development. 50% of women with Turner syndrome have a “classic” karyotype 45, XO. In this case, the analytical sensitivity and specificity of the test is 99%. In cases where the patient has a high level of mosaicism 45, XO / 46, XX, as well as structural abnormalities of the second X chromosome, the level of accuracy of the study may be reduced.
Sickle cell disease (SCD) or sickle cell anemia is an autosomal recessive over dominant genetic blood disorder characterized by abnormal red blood cells (erythrocytes) resistant, sickle-shaped (Orkin & Bauer, 2019). Sickle cells reduce their flexibility and elasticity, which increases the risk of various complications. The cause of the appearance of sickle-shaped cells is mutations in the hemoglobin gene.
If the sister and the mother’s first child were diagnosed with sickle cell anemia, it means that the grandparents of the daughters on the mother’s side had a similar AS genotype. Therefore, although the mother does not have a disorder, she is a sickle cell anemia carrier with a set of AS chromosomes:
The father’s genotype can be expressed in two ways: SS (completely healthy) and AS (is a carrier). However, the first case is impossible since, with it, the child’s ability to inherit the disease is impossible:
In all cases, the child will either be wholly healthy or be only a disorder carrier. Since the first child has sickle cell anemia, both parents are carriers of the AS genotype. In this case, the child’s chance of having AA genes and disorder is 25%.
Huntington’s disease is an autosomal dominant disorder characterized by chorea development, neuropsychiatric symptoms, and progressive cognitive impairment, usually beginning in middle age. Huntington’s disease is one of the most common neurological disorders caused by a single gene mutation. This disease’s features – the deposition of a protein aggregate in nerve cells – are inherent in Alzheimer’s disease and Parkinson’s disease (Malek & Newman, 2017). Since the condition is prevalent, this means that one chromosome is sufficient for it to be inherited. Accordingly, if the father was diagnosed with the disease, Punnet square for this case will look like this:
In this case, H is the gene for Huntington’s disease, and h stands for healthy chromosomes. As the graph shows, there is a 50% chance that a couple will have a child with the disorder.
References
Gravholt, C. H., Viuff, M. H., Brun, S., Stochholm, K., & Andersen, N. H. (2019). Turner syndrome: mechanisms and management. Nature Reviews Endocrinology, 15(10), 601-614. Web.
Lannoy, N., & Hermans, C. (2020). Genetic mosaicism in hemophilia: A practical review to help evaluate the risk of transmitting the disease. Haemophilia, 26(3), 375-383. Web.
Malek, N., & Newman, E. J. (2017). Hereditary chorea–what else to consider when the Huntington’s disease genetics test is negative? Acta Neurologica Scandinavica, 135(1), 25-33. Web.
Orkin, S. H., & Bauer, D. E. (2019). Emerging genetic therapy for sickle cell disease. Annual review of medicine, 70, 257-271. Web.