Human Genetics and Disorders

A defective gene is an internal factor because it originates within the organism's own genetic material. Internal factors include genetic predispositions, hormonal imbalances, and metabolic issues that originate inside the body. Extrinsic factors come from outside the body, like environment or lifestyle.

Influenza is an infectious disease caused by a virus, not a genetic disorder. Hemophilia, sickle-cell anemia, and night-blindness are genetic diseases caused by inherited gene mutations.

Hydrops fetalis, specifically Hb Barts hydrops fetalis, results from homozygous alpha-globin gene deletion (--/--). Without alpha chains, gamma chains form Hb Barts (gamma4) which has extremely high oxygen affinity, causing severe tissue hypoxia and fetal death. Beta-globin defects cause other thalassemias but not hydrops fetalis.

Human males have one X chromosome from the mother and one Y chromosome from the father, resulting in XY sex chromosomes. Females have two X chromosomes (XX). The Y chromosome determines male development.

Human cells have 23 pairs of chromosomes, including 1 pair of sex chromosomes (either XX in females or XY in males). The other 22 pairs are autosomes that carry most genetic information.

Human somatic cells contain 46 chromosomes (23 pairs), while gametes (sperm and egg) have 23 chromosomes. This diploid number (2n=46) is characteristic of human cells.

Tumour suppressor genes code for proteins, which normally control progression through a cell cycle checkpoint. These genes only contribute to a cancer when both copies are mutated in a way, which produces an inactive protein product. A single mutation inactivating one gene only has no effect. They contribute to cancer because the absence of the protein product removes controls on cell division.

An oncogene is a mutated form of a normal cellular gene (the proto-oncogene) that codes for a protein, which is either controlled abnormally, so that it is expressed in abnormally large amounts or has gained activity. It is more active than the normal protein.

Mutations in the APC (adenomatous polyposis coli) gene cause both classic and attenuated familial adenomatous polyposis. These mutations affect the ability of the cell to maintain normal growth and function. Cell overgrowth resulting from mutations in the APC gene leads to the development of multiple colonic polyps. These polyps are not themselves malignant but are prone to develop frank carcinoma through the accumulation of further genetic mutations.

Cancer is regarded as a genetic disease because it is caused by mutations in the genome. However, these mutations are normally in somatic cells, not the germ cells and mutations contributing to cancer are rarely inherited. To form a malignant cancer, a cell must acquire a small number of mutations (probably about six) each of which gives the cell a growth or survival advantage.

By far, the vast majority of autoimmune diseases involve multiple genes together with environmental factors. IPEX is an example of an extremely small number of autoimmune diseases that are caused by a single gene defect. In this case, mutation of the Foxp3 gene results in a profound defect in regulatory T-cell activity.

Gamma C deficiency is responsible for about 40% of cases of SCID, and together with JAK 3 deficiency, results in a T-B+NK- phenotype. It is also utilized by the receptors for IL-2, -4, -7, -9 and -21.

Tum cell lines are those which have mutated such that they cannot be grown in syngeneic animals with a normal immune system.

In the above question the only immune deficiency disorder that is related with an abnormality exclusively of the humoral response is Bruton's agammaglobulinemia.

A point mutation leads to a single amino acid substitution at either position 12, 13 or 61. These mutations are found in over 90% of patients with pancreatic carcinomas, in 40% of patients with colorectal cancers and their preneoplastic lesions, in acute myeloid leukemia (AML) and in preleukemic syndromes.