What is a defect or condition that is present at birth, does NOT automatically mean genetic
-HIV, passed from someone else, from mom to baby
Congenital
What is a disease/defect/condition that has a genetic basis, is passed on from parent to offspring (familial)
-based in genetic code
Hereditary
_________ arise from a mutation (permanent change) in a persons DNA
- passed on to offspring if the change occurs in the parent’s gametes (germ cells; egg or sperm)
- those that occur in cells other than germ cells are not passed on but are often stimm important
Genetic diseases
What are three ways a single gene mutation is changed in POINT?
- silent/conservatice-no change in amino-acid
- missense-different amino acid (sickle cell)
- nonsense-stop codon (truncated protein)
What are the two ways a single gene defect can occur in frameshift mutation?
- insertion-addition of nucleotides
- deleltion-loss of nucleotides
What is a single gene defect that can occur in trinucleotide repeat?
- amplication of a set of three
- fragile X syndrome
What are the transmission patterns of single-gene disorders?
Follow mendelian rules:
- Autosomal dominant
- Autosomal recessive
- X-linked
What is autosomal dominant?
Only one copy of mutant allele (D) results in disease manifestation
-mutant allele is dominant over normal allele
How can you tell that a pedigree is autosomal dominant?
- every generation has an effected person
- both males and females are affected
New AD mutations will manifest in the first generation. Whereas AR mutations will not manifest until the _______ generation
Second
Autoisomal dominant inheritance is reduced pentrance. What does that mean?
-the proportion of herterzygotes who show manifestations
Heterzygote: an individual having two different alleles of a particular gene or genes, and so giving rise to varying offspring
Autosomal dominant inheritance has variable expressivity. What does that mean
Expressivity is the degree (severity) of manifestations
AD inheritance has delayed age onset. What does that mean?
usually permit survial into adulthood (otherwise allele would cease to exist in the population)
Is loss of enzyme activity normal or rare in AD diseases?
Rare in AD diseases
-50 % activity is adequate for most enzymes
in AD inheritance what are genes usually encoding?
Structural proteins
-fibrillin 1 (Marfan syndrome)
What is this syndrome?
- a defect in fibrillin, a structural protein that is found in elastic fibers in various tissues (collagen)
- cause of chest pain/sudden death in young adults due to aortic dissection
Marfan’s Syndrome
What are the odds for each child in Autosomal recessive?
The odds for each child are:
25% chance of being affected
75% chance of being unaffected
–unaffected but still have potential to pass it on
50% chance of being a carrier as both parents are.
66% chance that an unaffected child is a carrier.
*because two copies of the mutant allele are needed to be affected
In what disorders are:
Penetrance and expressivity tend not to vary significantly.
New mutations (asymptomatic heterozygotes).
Consanguinity is commonly involved.
-cousins marrying cousins-so you have more instances of recessive alleles
Generation skipping is seen.
-because you need both recessive genes to come together
Autosomal recessive diseases
How are autosomal recessive disorders most comonly caused?
A defect in an enzyme in some metabolic pathway– most are METABOLIC problems
– A defect in a protein that makes it function less well
What are some hints that tell you the trait is autosomal recessive trait in a pedigree?
Hints that a pedigree is from an autosomal recessive trait:
- disease skips generations
- diseased patient has normal parents
- both males and females are affected
What is this disease?
Autosomal recessive inheritance
1:25 Caucasian adults are carriers
– 1:3200 live births
Mutations in CFTR channel
– Over 1000 mutations described.
– Most common (~66%) is ΔF508:
• 3‐base deletion of codon 508 resulting in a CFTR protein that lacks phenylalanine and is rapidly degraded.
Cystic Fibrosis
What is this disease?
• Organs affected
– Lungs: Bronchialobstruction,recurrentand severe pneumonias, especially with P. aeruginosa
– Pancreas – malabsorption, pancreatitis.
– Small intestine: obstruction (meconium
ileus).
– Reproductive tract: Male infertility in 95%.
– Skin: excessive NaCl excretion.
• Diagnosis
– Elevated sweat chloride
– Genetictestingforthecommonmutations
Cystic Fibrosis
What are X-linked disorders?
- Genes on the X chromosome are also susceptible to mutations.
- These mutations may be recessive or dominant. – X‐linked dominant disorders are very rare.
- Males are hemizygous for the X chromosome.
What is some evidence that tells you X-linked recessive inheritance?
Only males are affected by the trait
All daughters of affected males are carriers.
All sons of affected males are unaffected and are not carriers.
