Below is a list of protein mutations discovered in humans. Missense mutations ar

Question

Below is a list of protein mutations discovered in humans. Missense mutations are given as 'Normal amino acid--position within protein--Mutated amino acid'. For example, C18R means that a cysteine at position 18 in the human PDX1 protein is mutated to arginine. Frameshift mutations are denoted by 'fs'. For example, Pro63fsdelC means that a cytosine DNA base is deleted which normally is found in the codon for proline 63.

Using your multiple sequence alignment as a guide and your knowledge about the functional domains of PDX1, predict whether each of these mutations are likely to be pathogenic or nonpathogenic and explain why. In your answer, reference the chemical nature of the amino acids in question, as well as the conservation and functional domains of the protein.

C18R
Ins P46 (a proline insertion at position 46)
Q59L
Pro63fsdelC (a frameshift which deletes a cytosine base at codon 63)
D76N
P95Q
A140T
E178G
R197H
V220D

Copy this table into a Word processing document, fill it out, and paste into the answer box below.

Domain

Conserved?

Similar Chemical side chain?

Likely to be pathogenic?

C18R

Ins P46

Q59L

Pro63fsdelC

D76N

P95Q

A140T

E178G

R197H

V220D

CLUSTAL O(1.2.1) multiple sequence alignment (use as a guide to answer the question)


zebrafish_PDX1        MNREEHYYPPNHLYKDSCAFQRHPNEDYSQNPPPCLYMRQAH-------SVYASPLGAQD
house_mouse_PDX1      MNSEEQYYAATQLYKDPCAFQRGPVPEFSANPPACLYMGRQPPPP--PPPQFTSSLGSLE
Norway_rat_PDX1       MNSEEQYYAATQLYKDPCAFQRGPVPEFSANPPACLYMGRQPPPP--PTPQFAGSLGTLE
cattle_PDX1           MNREEQYYAATQLYKDPCAFQRGPAPDFSASPPACLYMGRQPPPPPPPPPPFPGALGALE
dog_PDX1              MNSEEQFYAATQLYKDPCAFQRGPAPEFSASPPACLYMGRQPPPP---PPPFPGTLGALE
Human_PDX1            MNGEEQYYAATQLYKDPCAFQRGPAPEFSASPPACLYMGRQPPPP--PPHPFPGALGALE
Rhesus_PDX1           MNGEEQYYAATQLYKDPCAFQRGPAPEFSASPPACLYMGRQPPPP--PPPQFPGALGALE
                     ** **::* .:**** ***** * ::* .** **** :           : . **: :

zebrafish_PDX1        QPNLTDITSYNMSS--RDDLAGPHLHLPQTSQ--TSLQSLGGYGDSL--DLCGDRNRYHL
house_mouse_PDX1      QGSPPDISPYEVPPLASDDPAGAHLHHHLPAQLGLAHPPPGPFPNGTEPGGLEEPNRVQL
Norway_rat_PDX1       QGSPPDISPYEVPPLA-DDPAGAHLHHHLPAQLGLAHPPPGPFPNGTETGGLEEPSRVHL
cattle_PDX1           QGSPPDISPYEVPPLA-DDPAMAHLHHHLPAQLALAHPPAGPFQDGADPGALEEPGSVQL
dog_PDX1              QGSPPDISPYEVPPLA-DDSAVAHLHHHLPAQLALPHPPAGPFPEGAEPAALEEPSRVQL
Human_PDX1            QGSPPDISPYEVPPLA-DDPAVAHLHHHLPAQLALPHPPAGPFPEGAEPGVLEEPNRVQL
Rhesus_PDX1           QGSPPDISPYEVPPLA-DDPAVAHLHHHLPAQLALPHPPSGPFPEGAEPGVLEEPNRVQL
                     * . **: *::     ** * ***    :*        * : :.       :    :*

zebrafish_PDX1        PFPWMKSTKSHTHAWKGQWTG-PYMVEAEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
house_mouse_PDX1      PFPWMKSTKA--HAWKGQWAGGAYTAEPEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
Norway_rat_PDX1       PFPWMKSTKA--HAWKSQWAGGAYAAEPEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
cattle_PDX1           PFPWMKSTKA--HAWKGQWAGGAYAAEPEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
dog_PDX1              PFPWMKSTKA--HAWKGQWAGGAYVAEPEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
Human_PDX1            PFPWMKSTKA--HAWKGQWAGGAYAAEPEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
Rhesus_PDX1           PFPWMKSTKA--HAWKGQWAGGAYAAEPEENKRTRTAYTRAQLLELEKEFLFNKYISRPR
                     *********: ****.**:* * .* ********************************

zebrafish_PDX1        RVELALTLSLTERHIKIWFQNRRMKWKKEEDKRRARGV--------DPEQDSSITSGDLK
house_mouse_PDX1      RVELAVMLNLTERHIKIWFQNRRMKWKKEEDKKRSSGTPSGGGGGEEPEQDCAVTSGEE-
Norway_rat_PDX1       RVELAVMLNLTERHIKIWFQNRRMKWKKEEDKKRSSGTTSGGGGGEEPEQDCAVTSGEE-
cattle_PDX1           RVELAVMLNLTERHIKIWFQNRRMKWKKEEDKKRSCGPPAAGGGDAEPEQDCAVTSGEE-
dog_PDX1              RVELAVMLNLTERHIKIWFQNRRMKWKKEEDKKRSCGTAPGGVADAEPEQDCAVSSGEE-
Human_PDX1            RVELAVMLNLTERHIKIWFQNRRMKWKKEEDKKRGGGTAVGGGGVAEPEQDCAVTSGEE-
Rhesus_PDX1           RVELAVMLNLTERHIKIWFQNRRMKWKKEEDKKRGGGTAVGGGGVAEPEQDCAVTSGEE-
                     *****: *.***********************:*. *         :****.:::**:

zebrafish_PDX1        DESCVGTATLAGPPSP-----LHPHAPSVQQDS------------------------
house_mouse_PDX1      --------LLAVPPLPPPGGAVPPGVPAAVREGLLPSGLSVSPQPSSIAPLRPQEPR
Norway_rat_PDX1       --------LLALPKPPPPGGVVPSGVPAAAREGRLPSGLSASPQPSSIAPLRPQEPR
cattle_PDX1           --------LLALPPPPPPGGAVPPAGPSAAREGRLPPGLSASPQPSSVAPLRPQESR
dog_PDX1              --------LLALPPALPPGGAVPPAVPAAAREGRLPPGLSASPQPSSVAPVRPQEPR
Human_PDX1            --------LLALPPPPPPGGAVPPAAPVAAREGRLPPGLSASPQPSSVAPRRPQEPR
Rhesus_PDX1           --------LL--PPPPPPGGAVPPAAPVAAREGRLPPGLSASPQPSSVAPRRPQEPR
                              * *        :    * . ::.      

Domain

Conserved?

Similar Chemical side chain?

Likely to be pathogenic?

C18R

Ins P46

Q59L

Pro63fsdelC

D76N

P95Q

A140T

E178G

R197H

V220D

Explanation / Answer

C18R non pathogenic.

Pro63fsdelC pathogenic

A140T pathogenic

P95Q pathogenic

Related Questions

Navigate

• Browse (All)
• Browse B
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.