Genetic Disease Flashcards
(50 cards)
What does alteration in the genetic code cause?
Mutations
How does permanent damage in the DNA affecting germ cells come to be?
Can be inherited
What does Permanent DNA damage in Somatic cells cause?
May result in tumor or developmental abnormality
__________ is a a single base substitution.
Point mutation
_______ is an insertion or deletion of 1-2 base pairs.
Frameshift
____ is an amplification of a 3-nucleotide sequence.
Trinucleotide repeat
What other 3 factors can impact protein coding Gene function?
- Polymorphisms
- Epigenetic changes
- Alterations in Non-coding RNA’s
What are the types of Genetic disorders?
- Mendelian Disorders
- Autosomal Dominant
- Autosomal Recessive
- Sex-linked (x-linked) disorders
- Disorders with multifactorial (polygenic inheritance)
- Cytogeneic Disorders (chromosomal aberrations) (autosomes and Sex chromosomes)
Tell me about autosomal dominant disorders….
- Mutated gene on ONE of the autosomes
- Expressed in heterozygous state, one parent usually affected.
- Often present with outward physical changes, but these may have delayed age of onset (Huntingtons disease)
What is reduced or incomplete Penetrance?
An autosomal dominant occurrence where a person has a mutant gene but either doesn’t, or only partially expresses it phenotypically.
What is Variable expressivity?
If the expression can be identified in all affected persons but to differing extents.
What is New or De novo mutation?
If neither parent is affected/no family history.
_______ is an Autosomal disease with nearly 1000% penetrance yet variable expressivity.
Neurofibromatosis (Bumps all over face)
Which is the larges group of Medelian disorders?
Autosomal Recessive
Tell me about Autosomal recessive disorders…
- Affect patients are homosygous; Parents appear unaffected.
- 25% of offspring are affected; 50% of offspring are carriers
- If the Recessive gene is rare in the population, disorder may be the result of consanguinity.
Many AR conditions are _________ defects leading to ______.
Enzyme defects leading to Metabolic dysfunction.
* Heterozygous patients are unaffected clinically as they typically have reduced but still adequate levels of the normal functional enzyme.
When is age of onset with AR disorders?
Early, complete penetrance is also common
Tell me about X-linked Disorders….
- all are not the X Chromosome
- Most are recessive
- Females having two x chromosomes are usually unaffected heterosygous carriers
- Males being hemizygous, will express the disorder.
- Y chromosome only carries one significant gene SRY (sex determining region)
What is an example of x-linked disorder?
Hemophilia A
What is lyonization?
16 days post conception most of one X chromosome in the female zygote is inactivated randomly resulting in the formation of a Barr Body in each cell.
*All progeny of that cell will carry the same inactivated X chromosome
What are the Diseases caused by Mutations in Structural proteins?
- Marfan Syndrome
- Ehlers-danlos syndromes
Tell me about Marfan Syndrome….
- Autosomal dominant
- Prevalence 1 in 5000
- Mutation of FBN1 gene resulting in abnormal fibrin, a glycoprotein necessary for normal elastic fiber production.
What are the characteristics of Marfan Syndrome?
- Tall thin body
- Abnormally long legs
- Arachnodactyly
- dislocation of lens of eye
- aortic aneurysm and dissection leading to heart failure and aortic rupture.
Tell me about Ehlers-Danlos Syndromes..
- At least 6 clinical variants of disease
- Problem with collagen synthesis, among 30 distinct types of collagen.
- Variable tissue distribution of these collagens may explain clinical heterogeneity of EDS’s
