pedigrees

24/10/26

modes of inheritance

• autosomal dominant

• autosomal reccessive

• X-linked Dominant

• X-linked Recessive

• Y-linked

• mitochondrial linked

autosomal dominant inheritance

• typically appear in every generation

• everyone who has it must have a parent with it

  • except on the off chance of a mutation (won’t see on test)

• no sex bias

autosomal recessive inheritance

• individuals with this trait must be homozygous for it

• big clue is that offspring with trait have unaffected parents

  • this makes both parents carriers

• no sex bias

• become more common with inbreeding

• rare, so individuals outside family unlikely to have it

X - linked dominant

• rare, so individuals outside family are unlikely to have the trait

• sex bias toward females, but males also affected

• an affected male passes to all of his daughters

• never ever have father-son transmission

X- linked recessive

• trait is biased to appear in males (who only need one X, ergo 50% more likely to have it)

• trait tends to skip generations

• don’t be fooled by a small pedigree, a sex bias may seem to exist if there’s two generations

polygenic trait

a trait that shows continuous variation due to the involvement of many different genes in its determinance.

genetic loci

the physical location of a gene on a chromosome. plural form is loci “low-sigh“

genome

all of the DNA and thus all genes in an individual or particular species

autosomal recessive disorder examples

• tay sachs disease

• sickle cell anaemia

• cystic fibrosis

tay sachs disease

• autosomal recessive

• mutation: allele change in the HEXA gene on chr15

• Hexosaminidase A (hex A) enzyme is not synthesized, causing inability to break down fat in neurons

• fatty compound builds up in neurons

• most sever form affects babies when they are only a few months old, with delayed development, loss of vision, abnormal reactions when startled, paralysis gradually sets in, may go deaf, have seizures, and ultimately unable to swallow or breathe

• the juvenile form (ages 2-10): less sever, clumsiness, loss of co-ordination, speech decline, life threatening issues in teens

• late-onset form: very rare and milder: muscle weakness, speech and balance issues, but may have reproduced and passes allele

sickle-cell anemia

• autosomal recessive

• mutation: HBA gene on chr11

• phenotype: cannot make hemoglobin protein cannot bind oxygen to red blood cells), misshapen RBCs, cannot pass easily through blood vessels

• accompanied by fatigue, severe pain from blood vessel blockages, jaundice, swelling, stroke

• carriers can have mild symptoms

• treatments to reduce symptoms, but cure would be bone marrow or stem cell transplants or gene therapy

origin of sickle-cell anemia

the mutated HBA allele is highly prevalent in the black community or people of African descent

• evolutionary mutation: it helps those survive against malaria, as sickle-cell individuals are highly resistant to malaria, and therefore live to increase the allele freq.

• the malaria parasite typically enters a healthy, flexible red blood cell, where is safely multiples by consuming hemoglobin until it bursts the cell to spread the infection throughout the body

• sickle-cell’s defense: the parasite’s presence drops oxygen levels, causing the abnormal hemoglobin to clump and warp the cell, which starves the parasite of nutrients and forces the spleen to destroy the cell before the infection can spread

cystic fibrosis

• autosomal recessive

• mutation: CFTR gene on chr7

• phenotype: dysfunctional channel protein lining lungs that normally regulates salt and water movement to maintain protective layer of mucus causing build up of mucus allowing chronic infections

• treatments: molecular chaperone drugs force CFTR protein to adopt its proper shape, drugs that keep the channel open

autosomal dominant disease examples

• huntington’s disease

• saethre-chotzen syndrome

huntington’s disease

• autosomal dominant

• mutation in huntington gene on chr4

• phenotype: huntington protein aggregates in neurons, forming clumps, causing healthy cells to die, leading to shaking, personality changes, and then death (within ~15 years)

• treatments: treat the symptoms, cannot cure the disease YET, clinical trials in gene therapy

saethre-chotzen syndrome

• autosomal dominant

• mutation in TWIST1 gene on chr7, a developmental gene

• phenotype: a range of severities; skull bones fused at birth, high forehead, droopy eyelids, webbing on hands and feet, short stature, MOST have normal intelligence

• treatments: no cure, surgeries to realign skull and for other corrective measures. considering differing severities, parents with this syndrome are recommended to do selective IVF so that the child doesn’t carry the mutation

x-linked recessive disease list

• hemophilia A

hemophilia A

• X-linked recessive

• mutation in: FVIII or FIX blood clotting genes

• phenotype: excessive bleeding from cuts or injuries, spontaneous bleeding into joints/deep muscles. easy bruising and internal hemorrhages → death

• treatments: injection of lab-made clotting factor, medication that mimics clotting factor, gene therapy

X-linked dominant disease list

• hypophosphatemia (vitamin D resistant rickets)

hypophosphatemia (vitamin D resistant rickets)

• x-linked dominant

• mutation in: PHEX gene

• phenotype: PHEX gene encodes an enzyme in bone and teeth, controls phosphate levels in blood, kidneys stop absorbing phosphorus, so blocks vitamin D activation

  • rickets: body lacks the raw materials needed to harden bones, ergo bones can’t take up calcium, meaning bowed legs, and small stature

• treatments: phosphate and vitamin D supplements

the only Y-linked condition Y chromosome infertility condition

• y-linked

• caused by microdeletions (not exactly mutation) on the Y chromosome in the AZF region

  • which means an inability to produce proteins for sperm cell development

• phenotype: cannot produce many sperm, slightly smaller testicular volume, normal male phenotype otherwise