Genetic Disorders

Chromosomes are gene-carrying structures located in the nucleus.
Each unreplicated chromosome consists of one supercoiled DNA molecule (double helix).
Genes are DNA fragments with specific nucleotide sequences.
Human somatic cells (non-reproductive) have 46 chromosomes.
Gametes (egg and sperm) have 23 chromosomes.
Homologous chromosomes (from mother and father) pair up during meiosis (Prophase I), having the same length, shape, and genes for inherited traits.
The number of chromosomes varies across species (e.g., bacteria, fruit flies, dogs, cats, apples, mosquitoes).
Errors in chromosome number can have significant effects, especially in animals.
Plants are more tolerant to changes in chromosome number (polyploidy).
Examples of polyploidy plants: wheat, strawberry, potato, cabbage.

Karyotyping is a technique to analyze chromosomal composition.
A karyotype is a display of an individual’s chromosomes arranged in homologous pairs.
Karyotyping identifies extra or missing chromosomes or missing chromosome pieces.
Karyotyping involves inducing somatic cells into metaphase, staining the chromosomes, and arranging them in pairs.
Karyotyping can be performed on a fetus using amniocentesis or chorionic villus sampling (CVS).
Amniocentesis: A needle is inserted into the uterus (14th-16th week) to remove amniotic fluid for testing.
CVS: A suction tube is inserted into the uterus (8th-10th week) to remove chorionic villi from the placenta.
CVS provides faster results than amniocentesis.
Fetoscopy: A minimally invasive technique for surgical access to the fetus and placenta to obtain fetal samples and assess health.
Ultrasound: A non-invasive technique that uses sound waves to create fetal images for assessing growth, development, and abnormalities.

Typical human male karyotype: 22 pairs of autosomes and one X and one Y chromosome.
Typical human female karyotype: 22 pairs of autosomes and two X chromosomes.

Genetic disorders are diseases caused by genetic abnormalities, leading to phenotypic changes and health problems.
Genetic disorders can be inherited through recessive traits, dominant traits, autosomal chromosomal alterations, sex-linked chromosomal alterations, and X-linked recessive traits.
Examples:
- Recessive: Albinism, cystic fibrosis
- Dominant: Huntington’s disease
- Autosomal chromosome alterations: Down syndrome, Patau syndrome, Edward’s syndrome
- Sex chromosome alterations: Turner syndrome, Klinefelter syndrome
- Chromosomal shortening (deletion): Cri du chat syndrome
- X-linked recessive: Color blindness, Duchenne muscular dystrophy, hemophilia

Recessively inherited disorder due to a missing enzyme for melanin production.
Individuals with albinism have a homozygous recessive genotype (aa).
Carriers are heterozygous (Aa) with a normal phenotype.
Mating between two carriers (Aa x Aa) results in a genotypic ratio of 1AA:2Aa:1aa.
Offspring have a 25% chance of inheriting albinism (aa), a 50% chance of being carriers (Aa), and a 25% chance of having a normal phenotype (AA).
$Aa \times Aa$ produces $1AA:2Aa:1aa$ .

Recessively inherited disorder where homozygous recessive individuals (cc) exhibit the condition.
Causes abnormally thick mucus lining in the respiratory and digestive tracts.
Life-threatening but can be managed with antibiotics and mucus clearing.
Follows the Mendelian F1 monohybrid cross pattern.

Dominantly inherited neurodegenerative disease.
Onset occurs between 30-45 years of age.
Individuals with homozygous (HH) or heterozygous (Hh) alleles will develop the disease.
No treatment available, but genetic testing is possible.
Example:
- Mother is heterozygous (Hh), and father is homozygous recessive (hh).
- $\text{Mother (Hh)} \times \text{Father (hh)}$ results in 50% chance of offspring inheriting Hh and developing Huntington's and 50% chance of inheriting hh and not developing Huntington's.

Occurs in approximately 1 in 700 births.
Caused by an extra chromosome 21 (Trisomy 21) due to nondisjunction during meiosis.
People with Down syndrome often have heart conditions and are susceptible to respiratory infections.
Lower than average life expectancy.

Occurs in approximately 1 in 5000 births.
Caused by the absence of one sex chromosome (XO) due to nondisjunction in meiosis.
Individuals are phenotypically female but have underdeveloped female sex organs and are sterile.
Other features include short stature, webbed neck, sunken breastbone, and broad chest.
Typically does not cause mental delays.

Occurs in approximately 1 in 2000 births.
Males are born with an extra X chromosome (XXY) due to nondisjunction in meiosis.
Phenotypically male but possess feminine body features.
Physical characteristics include small male sex organs, long legs, short trunk, and sterility.
Usually of average intelligence.

Occurs in approximately 1 in 50,000 births.
Caused by a deletion of the tip of the 5th chromosome.
Infants have a cat-like cry.
Individuals have unusual facial features, trouble walking/talking, and may exhibit aggressive behavior.
Identified by Jerome Lejeune in 1963.

Red-green color blindness is most common and inherited as an X-linked recessive trait.
Males (XY) are more commonly affected than females (XX).
Fathers pass X-linked alleles to daughters but not sons.
Mothers pass X-linked alleles to both sons and daughters.
Females must be homozygous (XnXn) to express the phenotype, otherwise, they are carriers (XNXn).
Males need only one copy of the allele (XnY) to exhibit the phenotype.

Serious X-linked recessive disorder causing progressive muscle weakening and loss of coordination.
Females must be homozygous recessive (XdXd) to exhibit the disorder.
Males express the trait if they carry the recessive allele on the X chromosome (XdY); 99% of affected boys develop the disorder.
Caused by the absence of dystrophin, leading to muscle degeneration.
Symptoms start between ages 2 and 6.
Affected individuals rarely live past their early 20s.
Gene therapy and stem cell research show promise.

X-linked recessive disorder characterized by a partial or complete loss of essential blood clotting factors.
Prolonged bleeding due to slow clot formation.
Types A and B depend on the specific clotting factor deficiency.
More common in males.
Treatment involves intravenous injections of the missing clotting factor.