Section IIE Flashcards
(27 cards)
How is X inactivation random, fixed and imcomplete?
- Random: Each cell chooses which X chromosome to inactivate so different cells my choos a maternal or paternal X
- Fixed: Once the X is inactivated it is not longer activated unless in gamete production in females
- Incomplete: X chromosome is not completely inactivated which explains the disease phenotype in people with abnormal numbers of sex chromosomes
What are the characteristics and examples of an X-linked recessive trait?
- Mostly males are affected (common to see a female affected followed by all males)
- absence of father-to-son transmission.
- Hemophilia A, DMD, red-green color blindness
What are the characteristic of an X linked dominant disease?
- KEY: Affected fathers will transmit to ALL of their daughters.
- becuase one X from each parent and father only has one X to give.
What is the purpose of the XIST gene?
-encodes an RNA transcript that coats the Barr body (inactivated X chromosome)
What is the purpose of GC methylation in barr bodies?
-GC dinucleotide methylation serves to maintain inactivation of the X chromosome
What are the father-to-son transmission patterns in X-linked and Y-linked diseases?
X-linked: No father to son transmission
Y-linked: always father to sone transmission
What gene is defective in hemophilia A and what are the symptoms?
- Gene for Factor VIII
- Bleeding (bruising, hemorrhaging, into joints, all kinds of bleeding)
What is the differnece in mutation between a mild and severe hemophilia?
- mild generally results from a missense mutation
- severe generally results from a nonsense or frameshift mutation
What gene is dysfunctional in DMD?
-The DMD gene which encodes Dystrophin
What is the significant of dystrophin?
- Dystrophin (encoded by the DMD gene) is an important structural protein of muscle cells.
- when it is dificient or absent, muscle cells are unable to maintain their integrity and lyse
What is the significant of CK in people with DMD?
-Creatine Kinse levels are elevated (up to 20x) due to the instability of muscle cells.
What is the inability to precieve green?
deuteranopia
What is the inability to precieve red?
-protanopia
What is the causitive factor in color blindness?
-unequal crossover of the red and green genes
What are three X-linked dominant disorders?
- hypophophatemic rickets: kidneys can’t reabsorb phosphate–> abnormal ossification
- incontinentia pigmenti: abnormal skin pigmentation that FOLLOWS DERMATOMES–>only females are born
- Rett Syndrome: autism, ataxia, mental retardation
What is unusual about the inheritance pattern of fragile X syndrome?
-Daughter of normal transmitting males were never affected bu the sons of those daughters were affected.
How do expansion repeats explain the sherman paradox in fragile X?
-expansion repeats occur in femails so the carry males pass down the mutation and the females then amplify the repeat.
What gene is defective in fragile X? What are its ranges of mutation?
- FMR1 gene (has a normal CGG repeat for 6-50 bp)
- 50-200 repeats in normal transmitting males and their daughters
- >200 in fragile X (called a full mutation)
Does mitochondrial DNA have introns?
-no
What is heteroplasmy in reference to mtDNA?
-explain that a single cell can harbor some molecules that have a mtDNA mutation an others that do not.
What are the characteristic of LHON (mutation, heteroplasmy, symptoms)?
- Leber Hereditary Optic Neuropathy
- characterized by loss of the central visual field in the third decade of life
- missense mutation in mtDNA with little heteroplasmy
What are the characteristics of MERRF syndrome (mutation, heteroplasmy, symptoms)?
- myoclonic epilepsy with ragged-red fiber syndrome
- single base mutation in a tRNA gene
- heteroplasmic and highly variable
- epilepsy, dementia, ataxia, myopathy
What is MELAS?
-mitochondrial enchephalomyopathy and storke-like symptoms
What is similar between MELAS and MERRF?
-both highly heteroplasmic and variable
