Genetic Basis of Disease (PATHO 3#)

DNA

• DNA directs synthesis of proteins

• Made of one or more polypeptides

• Composed of amino acids

  • Twenty amino acids

  • Directed by sequence of bases (codons)

Mitosis purpose

• Growth, repair, and replacement of body (somatic) cells.

mitosis process

• DNA duplicates.

• The cell divides once → producing two identical daughter cells.

mitosis chromosomes

• Each daughter cell gets a full set of 46 chromosomes (23 pairs).

• These cells are genetically identical to the parent cell.

Meiosis purpose

Formation of sex cells (ova and sperm).

meiosis process

1. DNA duplicates.

2. Two successive cell divisions occur.

3. Result = four cells, each with 23 chromosomes (one from each pair).

meiosis chromosomes

• These are haploid cells (half the usual number).

• When an ovum (23) and a sperm (23) unite → the fertilized egg (zygote) has 46 chromosomes.

Gen XX or XY

Of the 23 pairs of chromosomes in each living human cell, 22 pairs are not involved in controlling a person’s biological sex

XY-Male

XX-Female

Mutation

• Any inherited alteration of genetic material

  • Single-gene disorders

  • Chromosomal disorders

  • Multifactorial disorders

Single-Gene Disorders: Autosomal dominant inheritance

only one parent has the gene to pass it onto their offspring

• If one parent is affected, 50% chance of being affected

• One of the parents is usually affected

• Male/Female equally affected

• If both parents are affected, all children will be affected

Marfan Syndrome

• Connective tissue disorder

• Affects aorta, heart valves and joints

• Individuals are usually tall in stature

• Risk of aortic dissection

Huntington Disease

• Neurological disorder

• Does not appear until adulthood

• Degeneration of neurons

Single-Gene Disorders: Autosomal recessive inheritance

Genes don’t produce abnormal traits unless both parents have the gene and pass them to their offspring

• Male and Female offspring affected equally

• If parents are carriers, each offspring has a one in four  chance of being affected

• If one parent is affected and the other is not a carrier all of the offspring will have the altered gene but not be affected

• If one parent is affected and the other is a carrier, each offspring will have a one in two chance of being affected and a one in two chance of being a carrier

Cystic Fibrosis

• Disrupts chloride transporter

• Build-up of mucus in the lungs

• Pancreatic dysfunction

Sickle Cell Disease

• Red blood cells (RBCs) become sickle-shaped under stress (low O₂, dehydration, infection).

• Sickled RBCs are stiff and sticky → block blood vessels (vaso-occlusion).

• RBCs break down faster (hemolysis) → chronic anemia.

Genetic adaptation

Cystic fibrosis is more common in caucasians and sickle cell is more common in african americans

• —> thought to protect against cholera

  • The CF carrier state may have given protection against cholera or typhoid fever, because the altered chloride channels helped prevent massive fluid loss during diarrheal illnesses.

• —> thought to protect against malaria

  • The sickled red blood cells make it harder for malaria parasites (Plasmodium falciparum) to survive and reproduce.

Sex-linked inheritance (males XY)

• Only have one X chromosome.

• If that X carries the recessive mutation, the male will express the disease (no backup copy).

1. 
   

1. Example: A male with XʰY has hemophilia.

Sex-linked inheritance females (XX)

• Need two copies of the mutated gene to have the full disease (XʰXʰ).

• If they only have one copy (XʰXᴴ), they are usually carriers.

• Some carrier females may show mild symptoms due to X-inactivation.

Sex-linked inheritance- sex-linked

• Typically refers to X-linked disorders (because Y-linked conditions are extremely rare).

• Classic nursing-relevant examples:

  • Hemophilia A & B

  • Duchenne muscular dystrophy

  • Fragile X syndrome

Dominant

• One affected parent

• If a father has an x-linked dominant disorder, all daughters will have the disorder and none of the sons

• If a mother has this, 50% chance of each child being affected

• Family hx may show miscarriages and predominance of female offspring

  • Commonly lethal in males

Recessive

• Most affects males with unaffected parents

• All of the daughters will be carriers of an affected father

• Sons of an affected male are unaffected

  • Sons can’t transmit the disorder

• Unaffected male children of a female carrier don’t transmit the disorder

X-Linked Dominant Inheritance

Less common than the recessive

X-Linked Dominant Diseases

Fragile X Syndrome

• Most common inherited cause of intellectual disability.

• Features: developmental delays, autism-like behaviors, long face, large ears.

• More severe in males, but females can also be affected.

X-Linked Dominant Diseases

Rett Syndrome

• Affects almost exclusively females.

• Features: normal early growth, then regression of motor/language skills, repetitive hand movements.

• Usually lethal in males (miscarriage or death shortly after birth).

Hypophosphatemic Rickets (Vitamin D-resistant rickets)

X-Linked Dominant Diseases

• Features: short stature, bowed legs, dental issues.

• Caused by phosphate wasting in kidneys.

• Both sexes affected if they inherit the gene.

X-Linked Recessive Inheritance- Hemophilia A

• Dad with hemophilia → all daughters = carriers, all sons = normal.

• Carrier mom + normal dad → 50% sons affected, 50% daughters carriers.

Hemophilia

Recurrent/prolonged bleeding, hemarthrosis (bleeding into joints).

Genetic counseling important for families.

Chromosomal disorders (Aneuploidy)

Deviations in either structure or the number of chromosomes

• Gain or loss of chromosomes usually due to nondisjunction of autosomes or sex chromosomes during meiosis

• When chromosomes are gained or lost, the name of the affected cell contains the suffix “-somy”

  • Trisomy (i.e. 21, down syndrome)

Down Syndrome

• Distinct facial features

• Cognitive developmental delays

Turners Syndrome

• Amenorrhea

• Infertility

• Short stature

Multifactorial

Caused by both genetic and environmental factors (i.e. cleft lip or palate)

• Chemicals

• Maternal age

• Infections

• Radiation

• Nutrition

• Health