Retinitis Pigmentosa (RP) is
an affliction to the eyes in which the rod cells in the retina
(used for peripheral vision) are damaged. RP is not a single disease
but rather a common name for a group of hereditary retina diseases
that cause night blindness and gradual degradation of the field of
vision, ultimately resulting in tunnel vision.
Night blindness is very common in the O'Brien family and Dr. Bashir, a
geneticist, has started research to find the cause of this disease.
So far, he has discovered that the disease is autosomal dominant and
he has isolated a part of the third chromosome of the patients that
differs from healthy people. This part of chromosome 3 contains the
gene that codes for rhodopsin, a protein involved in vision at
low-light conditions.
More knowledge of this protein may explain what causes night blindness
(and perhaps lead to a suitable treatment).
The rhodopsin genes of RP patients in the O'Brien family were isolated
and the DNA sequence was established. Dr. Bashir found several
mutations. Through a number of exercises, we will investigate the
consequences of each mutation step by step. You can use this form (Word | PDF) to
write down you answers.
Let's start by looking at the messenger RNA derived from the healthy human rhodopsin gene:
augaauggca cagaaggccc uaacuucuac gugcccuucu ccaaugcgac ggguguggua 60
cgcagccccu ucgaguaccc acaguacuac cuggcugagc cauggcaguu cuccaugcug 120
gccgccuaca uguuucugcu gaucgugcug ggcuucccca ucaacuuccu cacgcucuac 180
gucaccgucc agcacaagaa gcugcgcacg ccucucaacu acauccugcu caaccuagcc 240
guggcugacc ucuucauggu ccuagguggc uucaccagca cccucuacac cucucugcau 300
ggauacuucg ucuucgggcc cacaggaugc aauuuggagg gcuucuuugc cacccugggc 360
ggugaaauug cccugugguc cuuggugguc cuggccaucg agcgguacgu gguggugugu 420
aagcccauga gcaacuuccg cuucggggag aaccaugcca ucaugggcgu ugccuucacc 480
ugggucaugg cgcuggccug cgccgcaccc ccacucgccg gcugguccag guacaucccc 540
gagggccugc agugcucgug uggaaucgac uacuacacgc ucaagccgga ggucaacaac 600
gagucuuuug ucaucuacau guucgugguc cacuucacca uccccaugau uaucaucuuu 660
uucugcuaug ggcagcucgu cuucaccguc aaggaggccg cugcccagca gcaggaguca 720
gccaccacac agaaggcaga gaaggagguc acccgcaugg ucaucaucau ggucaucgcu 780
uuccugaucu gcugggugcc cuacgccagc guggcauucu acaucuucac ccaccagggc 840
uccaacuucg gucccaucuu caugaccauc ccagcguucu uugccaagag cgccgccauc 900
uacaacccug ucaucuauau caugaugaac aagcaguucc ggaacugcau gcucaccacc 960
aucugcugcg gcaagaaccc acugggugac gaugaggccu cugcuaccgu guccaagacg 1020
gagacgagcc agguggcccc ggccuaa 1047
Note: This is only a transcript of the coding part of the rhodopsin gene, from start codon (aug)
to stop codon (uaa). The complete gene on
the chromosome consists of exons (the parts that code for the actual
protein), introns (that do not code for proteins), and other sequences
at the 5' side (before the gene) and the 3' side that are not translated
to protein. The full human rhodopsin gene consists of 6953 bases.
The DNA sequence of rhodopsin can be translated to a 348 residue amino
acid sequence using a codon table.
Note: Amino acid sequences are usually given in the one-letter code.
You can review this code together with the drawings of the twenty amino acids.
Of course, we will not translate the entire gene by hand. In the next section we will look up the amino acid sequence for human rhodopsin in a protein database.
