Human Genetics and Disorders

The common gamma chain is encoded by the gene IL-2 receptor gamma, or IL-2Rγ, which is located on the X-chromosome. For this reason, immunodeficiency caused by mutations in IL-2Rγ is known as X-linked severe combined immunodeficiency. The condition is inherited in an X-linked recessive pattern.

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

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.

Lack of CD154 (CD40L) prevents signalling to the B-cell CD40 to bring about Ig class-switching away from IgM.

Large adenomas in vital hormone producing organs raise the hormones the organ produces leading to serious complications called paraneoplastic syndromes.

Replacement immunoglobulin therapy is also used in CD40 ligand deficiency. Ig is prepared from the plasma collected from a large number of normal individuals, usually between 10,000-50,000, who have been carefully screened to make sure they are healthy and do not harbor certain infectious diseases. The plasma contains a broad range of specific antibodies to many different types of bacteria and viruses.

The BRCA2 mutation is the most likely to be associated with male breast cancer.

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 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.

Fas forms the death-inducing signaling complex (DISC) upon ligand binding. Membrane-anchored Fas ligand trimer on the surface of an adjacent cell causes oligomerization of Fas.

EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

Determination of HLA haplotype is based on association of particular haplotype with risk of disease, particularly autoimmune disease. It does not diagnose disease, and finding at-risk haplotype does not guarantee that disease will eventually occur. Rather, it identifies individuals who are predisposed to disease.

10% is usually used as an indicator of risk sufficient to justify genetic testing for BRCA mutation.

Huntington disease displays age-dependent penetrance. So, her risk is now less than 50% though it is still possible that she will develop the disorder.

RET mutation is responsible for increased risk of medullary thyroid cancer as well as multiple endocrine neoplasia 2, in which pheochromocytoma and parathyroid adenoma also occur.

Decreased activity of TMPT leads to increased levels of active 6-mercaptopurine, since the drug is normally inactivated by the enzyme. This is associated with toxicity of the chemotherapeutic drug.