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NBME 20 Answers

nbme20/Block 1/Question#11 (38.5 difficulty score)
The sequence surrounding the first two exons ...
Disruption of normal splicing by creation of a new 3′ splice site🔍

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submitted by drdoom(884),
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sA seirdbdce in het equstion es,tm thsi mntoauit ucsorc wnihit an nrinto (a gene etenmsg ichhw si rabetnsdric DAN-;][gANt&R ubt ont )tladarnse.t NAR pcsilgni es)zeymn( grba RNA dna pool“ it;” an inotrn is tcu tou dna eht eoxns no hterie seid fo het tiornn are nded,oiaj leki i:hts

o1teoinx—2x—ronnne t=;g& 12oxenexn—o

a,pcyylliT tsih lciingps cursoc ta het veyr deges fo the onrtin thwa( I etdendo tiwh hte ”—“ ).hatreracc utB ni uro ,eacs a umntitoa tiwnih hte oinrtn is inuagsc ANR psiniglc yneemz to crnzogeei a new t:sei teh pceslir sutc nithwi teh rntnio sda(tien fo at het eryv d,gee as it ouhs.ld) oS, ew tge gteoisnhm htat lokso kile :this


atT’sh a yttallo nedftfeir NAmR olleu,cme dan i'ts niggo ot kmae our l-nbgoiβ petrino kolo nad( hv)eabe llywfua restga.n

drdanielr  I remember that in the pre-mRNA, the splicing sites of the intron where the spliceosome attaches are surrounded by "GU---AG" like "guac", so here the homologous DNA to this strand would be transcribed into "" and this would create a 3' slice site too soon +4  
vivarin  if this is supposed to be pre-mRNA, why are there T's in the sequence? I'm so confused by this for some reason +8  
sars  This is the gene (DNA), not heterogenous mRNA. +  

submitted by monoloco(136),
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siTh ahs to od tihw ontirn icpisng.l bermeemR TA.GG siTh iuttaonm dinduec na AG eolscr eherw ti was spoupesd ot ,eb so semo fo htat ntroni tjus eacebm na neox.

submitted by waterloo(74),

I interpreted "sequence surrounding first two exons of gene" - to mean they must be talking about introns. Three of the answer choices don't have much to do with introns.

  • missense mutation would have to be in the exon to cause change in amino acid.
  • polyadenylation is at the end of the mRNA
  • inhibition of replication is DNA

that may not be air tight, but helps narrow down. Also knowing some B-thalassemia is due to variants in abnormal splicing helps. (FA 2019 pg 43)

submitted by s1khwitit(1),

also remember that B-thalassemia is due to point mutations in splice sites and promoter sequences (FA19 pg410). If you create a mutation in a splice site you will surely mess up the correct mRNA needed to make a functional B-globin protein. That is how I answered the question.