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NBME 18 Answers

nbme18/Block 3/Question#32 (reveal difficulty score)
X-Ray of a newborn shows ribs associated with ...
Expression of a HOX gene normally expressed only caudal to C-7 🔍 / 📺 / 🌳

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submitted by sway(0),
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submitted by regents(4),
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okokok1  to add onto cervical ribs being abnormal, they are found to be one of the causes of thoracic outlet syndrome. +1  
kcyanide101  i am still confused over this answer. Please someone should help with a clarifying explanation. What makes overexpression of a HOX gene normally expressed C-7 wrong??? +  
drdoom  @kcyanide101: Your cervical vertebrae should NOT have ribs! (The neck vertebral bodies are normally “ribless”!) The growth of ribs (as well as other “segments” of the body) is governed by a very special family of genes known as the HOX genes. The HOX gene responsible for rib growth should only get expressed (“work”) AFTER C7. If, for some weird reason, it gets turned on in the development of the neck, you will get things growing where they shouldn’t be! +  
drdoom  If you really want to have your hair blown back, check out some images for “mutant HOX expression”: Enjoy! ;-) +  

submitted by an1(72),

I was so lost when I saw this. But I was able to break it down and figure out what's happening.

HOX is transcription from Head (cranial) —> Toe (caudal)

I think of this as “HBO is Sex from Head to Toe”: HBO shows have a lot of nudity and what not, the sex helps me think of HbO + seX = HOX; it's for arrangement from the head to the toe.

One of the cervical has become a thoracic looking segment. So we have replaced a cranial segment (cervical) with something closer to the feet/ caudal (thoracic)

So the Hox gene at the top is expressing caudal info when it should be cranial at C7

drdoom  here's a nice image, too: +  
drdoom  essentially, this question is describing a situation where the “orange genes” got turned on in the yellow area +  
drdoom  oh, it's not that ”the Hox gene” is expressing the wrong info, by the way; it’s that the WRONG Hox gene is being expressed. This can happen when the wildtype Hox gene (cervical area) is mutated and so the thoracic Hox gene “takes over” -- even though abnormalities happen, this mechanism protects the body from missing an entire segment (“better to put the wrong thing there than nothing at all!”) +  
an1  @drdoom how do we know this question was talking about HOX expressing the wrong info vs HOX being wrong itself? Since all the other segments are assumed to be normal. wouldn't they be affected too if HOX was wrong all around? +  
drdoom  Because HOX genes encode transcription factors. Each HOX transcription factor, in turn, governs many other genes (turns on some, represses others) which direct development of a segment. It’s unlikely a single mutation in a HOX gene “flips” it from directing cervical development to directing thoracic development. It's more likely that cervical HOX tf became dysfunctional (“Loss of Function” mutation), which results in thoracic HOX tf to “take over”. +1  
drdoom  Oh, I should have mentioned: each HOX box is a different/separate gene. It's not all one gene. It's a family of genes so a mutation in one will be independent of the others. +  

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