Human Genetic Disorders

General Information: Non-disjunction occurs when chromosomes fail to separate properly during cell division, leading to an abnormal number of chromosomes.
Associated with Maternal Age: The likelihood of non-disjunction increases with maternal age, specifically as eggs remain in Prophase I of meiosis for extended periods (40+ years). This can result in chromosome tetrads entwining, leading to incorrect separation during anaphase.

Mechanism: Caused by Trisomy 21, where there are three copies of chromosome 21.
Phenotypes: Characterized by short stature, round full face, oversized tongue, and variable degrees of intellectual disabilities.

Mechanism: Caused by Trisomy 13.
Phenotypes: Associated with severe neural tube defects, facial clefting (both cleft lip and cleft palate), polydactyly (extra fingers or toes), and significant intellectual disabilities.

Mechanism: Resulting from Trisomy XXY.
Phenotypes: Presents with underdeveloped testes leading to sterility and overdeveloped breast tissue; treatment may involve hormone therapy and surgery.

Mechanism: Involves Trisomy XXX.
Phenotypes: Most individuals are normal due to X-inactivation, where one X chromosome in each cell becomes a Barr body and is silenced. Symptoms include taller-than-average stature, clumsiness, and potential intellectual disabilities.

Mechanism: Results from Monosomy X (XO).
Phenotypes: Notable for unexplained short stature, a short, webbed neck, and swollen hands and feet at birth.

Mechanism: Resulting from a deletion on the short arm of chromosome 5 (5p-).
Phenotypes: Characterized by multiple developmental abnormalities, including a distinctive laryngeal defect leading to a cat-like cry.

Mechanism: Involves a mutation in the Hex A gene on chromosome 15 leading to dysfunctional hexosaminidase.
Implications: The inability to break down a type of fat in brain cells results in neurological degradation; it is more prevalent in Ashkenazi Jewish populations due to a smaller gene pool, with most affected individuals dying by age 5.

Mechanism: Linked to mutations in a gene on chromosome 11 that encodes the tyrosinase enzyme.
Implications: Without functional tyrosinase, melanin cannot be produced, leading to a lack of pigmentation in skin, hair, and eyes. Individuals have increased sensitivity to UV rays and must take precautions against sun exposure.

Mechanism: Caused by a mutation in the HBB gene on chromosome 11, leading to the production of hemoglobin S instead of hemoglobin A.
Phenotypes: Causes red blood cells to change shape (elongate and sickle); this can cause blockages in blood flow and painful crises. Hydroxyurea is a potential treatment. This condition has a higher incidence in individuals of African descent due to heterozygote advantage against malaria.

Mechanism: Involves a mutation that affects the Phenylalanine Hydroxylase enzyme (chromosome 12).
Implications: Inability to metabolize phenylalanine leads to toxic buildup that damages brain cells. Babies are tested at birth, and treatment involves a strict low-phenylalanine diet. Products containing aspartame, a sugar substitute containing phenylalanine, carry warning labels.

Mechanism: Caused by mutations in the CFTR gene on chromosome 7, which encodes for a protein that regulates chloride transport.
Phenotypes: Results in thick mucus buildup in lungs and digestive tract, leading to various severe health issues. New treatments include Trikafta, a combination of three drugs (elexacaftor, tezacaftor, ivacaftor) that help the CFTR protein function correctly and facilitate better chloride ion transport. Particularly effective for individuals with the F508del mutation, which results from a deletion of phenylalanine at position 508.

Mechanism: Caused by a triplet repeat expansion (CAG) in the HTT gene on chromosome 4.
Phenotypes: Associated with the degradation of brain cells and manifests later in life (usually after 30 years of age). Abnormal CAG repeats range from 37 to 86, compared to a normal range of 11 to 34.

Mechanism: Resulting from mutations in the FGFR3 gene (chromosome 4).
Phenotypes: The mutant protein prematurely converts cartilage to bone in long bones, leading to shortened limbs; genotypes include Dd (dwarfism), dd (normal height), DD (non-viable).

Mechanism: Caused by mutations in the FBN1 gene (chromosome 15), affecting fibrillin protein crucial for connective tissue integrity.
Phenotypes: Traits include tall stature, larger arm spans, and loose joints; notable individuals include Abraham Lincoln and Michael Phelps.

Mechanism: Caused by mutations affecting Factor VIII in the blood-clotting cascade.
Implications: Affected individuals cannot form blood clots; treatment involves administering clotting factors, which have been developed synthetically following the HIV crisis in the early 1980s.

Mechanism: Linked to mutations affecting the dystrophin protein on the X chromosome, crucial for muscle integrity.
Phenotypes: Results in muscle breakdown during early childhood.

Mechanism: Caused by mutations in one of the many gene receptors involved in color detection within the eye.
Phenotypes: The most common type is red-green colorblindness, which varies in severity based on the defective protein involved.

Mechanism: Caused by a triplet repeat expansion (CGG) affecting the FMR1 gene.
Implications: This protein is necessary for proper neurological development, with the severity of intellectual disability associated with the number of repeats present in the individual.