MicroRNA and inherited diseases Flashcards
(13 cards)
What are potential mechanisms of microRNA involvement in inherited diseases?
Point mutations in seed region, point mutations in target site, large mutations (deletions or duplications)
Limited experimental evidence suggests these mechanisms likely reflect serious debilitating effects of mutations at the germline level.
What is a characteristic of nonsyndromic progressive hearing loss?
Hearing loss only clinical feature, very frequent disorder with high genetic heterogeneity (>100 associated genes)
DFNA50 is an autosomal dominant deafness locus.
Which genes were excluded as associated with DFNA50?
UBE2H, SMO, ATP6V1F, CALU, CCDC136, TSPAN33, KLHDC10, C7ORF68, FLNC, IMPDH1, MIR129-1
These exclusions help narrow down potential genetic causes of the disorder.
What microRNA polycistron is present in the DFNA50 locus?
miR-96/miR-182/miR-183
This cluster may play a role in the hearing loss associated with this genetic locus.
What specific mutations were discovered in the MIR96 gene’s seed region?
+13 G > A transition at position 4, +14 C > A transversion at position 5
These mutations may influence the function of the microRNA.
What impact does experimental targeting have on microRNA?
Reduced silencing of actual targets, increased silencing of new targets
This indicates a potential for altering gene regulation through microRNA manipulation.
What mutation affects miR-189 binding in Tourette’s syndrome?
A mutation in the 3’ UTR of SLITRK1
This disruption affects gene regulation in neural pathways.
What is the miR-17~92 cluster composed of?
miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, miR-92a-1
These microRNAs are encoded by the MIR17HG gene.
What is the role of the miR-17~92 cluster in cancer?
Upregulation leads to cancer, complete inactivation (both alleles) leads to perinatal death
This cluster is considered a bona fide oncogene (oncomiR).
What are the key features of Feingold syndrome?
Autosomal dominant syndrome, microcephaly, relative short stature, digit anomalies
70% of cases involve loss-of-function mutations in MYCN.
What type of deletions were identified in non-MYCN cases of Feingold syndrome?
Deletions in MIR17HG
Hemizygous deletions result in only one allele being deleted.
What is the effect of haploinsufficiency of miR-17~92 in mice?
Recapitulates developmental abnormalities
This suggests the importance of miR-17~92 in developmental processes.
Which important signaling pathways are modulated by miR-17~92?
TGF-β and sonic hedgehog signaling pathways
These pathways control skeletal development and limb patterning.
