Comprehensive Notes on Kidney Disease, PKD, and Hedgehog Adaptations

Kidney disease impairs the body's ability to:
- Clean blood.
- Filter extra water.
- Control blood pressure.
- Affect red blood cell production and vitamin D metabolism for bone health.
Kidneys are located on either side of the spine, above the waist.
Kidney damage leads to:
- Waste and fluid buildup.
- Swelling in ankles, nausea, weakness, poor sleep, and shortness of breath.
- Kidney failure, which can be deadly if untreated.

Kidneys maintain homeostasis within the body.
Homeostasis is the process by which an organism maintains a stable internal environment (equilibrium), managing waste and restoring balance when disrupted.

PKD is an inherited disease causing cysts (abnormal sacs of fluid) to grow in the kidneys.
Excessive cyst growth damages the kidneys and can cause pain or infection.
Children of a parent with PKD have a 50% chance of inheriting the disease irrespective of gender.

Sex-linked recessive:
- Mother affected (XaXa), Father unaffected (XY)
- Genotypic %: XaX - 50%, XaY - 50%
- Phenotypic %: Affected - 50%, Unaffected - 50%
Autosomal dominant:
- Mother affected/ heterozygous (Aa), Father unaffected (aa)
- Genotypic %: Aa - 50%, aa - 50%
- Phenotypic %: Affected: 50%, Unaffected: 50%
Autosomal recessive:
- Mother affected (aa), Father unaffected/homozygous (AA)
- Genotypic %: Aa - 100%
- Phenotypic %: Unaffected - 100%
PKD follows an autosomal dominant mode of inheritance.

Normal and mutated PKD1 proteins exhibit structural differences.
Mutated proteins may not have the same function due to allele alterations.
Symptoms of PKD in pets (cats and dogs) include: increased drinking and urination, decreased appetite, weight loss, nausea, and vomiting

Pedigree analysis identifies families with autosomal dominant PKD.
Individuals in a pedigree that do not fit the autosomal dominant inheritance pattern indicate that the pedigree does not display an autosomal dominant mode of inheritance.
For a trait to be inherited, it must originate from the family lineage.

There are approximately 50 mutations in the PDK1 protein that lead to polycystic kidney disease.
Normal PDK1 gene sequence:
- AGG TCC GCA A
Replicated normal DNA strand:
- TCC AGG CGT T
Transcribed normal strand:
- A G G U C C G C A A
Mutated PDK1 gene sequence: GGT CCG CAA
Replicated mutated DNA strand: CAT CTA GGT CCG CAA
Transcribed replicated strand: GU A GAU CCA GGC GUU
Translated mRNA strand: VAl ASP PRO GLY VAL
Mutations identified:
- Missense
- Nonsense-to-Missense Mutation
The mutations affected the mRNA, removing a stop codon and altering amino acids, which affected protein length, structure, and likely caused loss of function. The loss of a premature stop codon extends the protein's length.
The mutated protein likely does not have the same function as the normal protein due to structural changes from amino acid alterations.

PKD has been described in the animal kingdom beyond humans, cats and dogs, including pigs, horses, rats, lambs and even hedgehogs!
Hedgehogs possess around 5,000 stiff, sharp, keratin-containing spines for defense.
They curl into a ball to deter predators when threatened.
Hedgehogs are nocturnal and primarily forage for food at night, relying on their senses of hearing and smell to find food.
They have strong rear legs with thick, long claws for digging underground dens and weaker paws and nails on their front legs.

Species D and E are most closely related as they branch off later and are less related to the ancestor than A and B
Species A and E are most distantly related as they are the farthest away and have more branches between them.

Geographic Isolation: Prevents mating between hedgehog species in northern Europe and Southern Africa.
Temporal Isolation: Different mating seasons (summer in Southern Africa, spring in Europe) prevent mating if the hedgehogs were placed together.
Behavioral Isolation: Not yet addressed in reference to hedgehogs.