FROM GENES TO GENETIC DISEASES: WHAT KINDS OF MUTATIONS MATTER?
Definitions

A gene is the basic physical and functional unit of heredity.

Genes, which are made up of DNA, act as instructions to make molecules called proteins.
http://ghr.nlm.nih.gov/handbook/basics/gene

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other
organisms. http://ghr.nlm.nih.gov/handbook/basics/dna

Mutation a permanent, heritable change in the nucleotide sequence in a gene or a
chromosome; the process in which such a change occurs in a gene or in a chromosome.
http://www.biology-online.org/dictionary/Mutation

Genetic Disease is the result of changes, or mutations, in an individual’s DNA
http://www.geneticalliance.org/diseases

Nucleotide is the basic building block of nucleic acids, such as DNA and RNA, and it is an organic
compound made up of nitrogenous base, a sugar, and a phosphate group.
http://www.biology-online.org/dictionary/Nucleotide

RNA (ribonucleic acid) has 3 groups (mRNA, tRNA, rRNA) and it codes for amino acid sequences.
http://chemistry.about.com/od/chemistryglossary/a/rnadefinition.htm

Transcription is the process of making a copy of an RNA sequence
https://www.genome.gov/27552603

Translation is the process of translating the sequence of a messenger RNA (mRNA) molecule to a
sequence of amino acids during protein synthesis.
https://www.genome.gov/27552603

Amino Acids are considered to be the building blocks of proteins.
http://chemistry.about.com/od/chemistryglossary/g/amino-acid-definition.htm

Codon a set of three adjacent nucleotides.
http://chemistry.about.com/od/chemistryglossary/g/amino-acid-definition.htm

Hydrophilic having an affinity for water; able to absorb, or be wetted by water
https://www.boundless.com/biology/definition/hydrophilic/

Hydrophobic is a property of a substance to repel water
http://chemistry.about.com/od/chemistryglossary/g/Hydrophobic-Definition.htm

Allele is an alternative form of a gene and is at a specific part of the chromosome
http://biology.about.com/od/geneticsglossary/g/alleles.htm
QUESTIONS
1. How does a gene become a protein? A gene becomes a protein through 3 processes. A
gene goes through transcription which makes the RNA molecule, and it goes through
translation which makes the mRNA molecule sequence. Then, the process protein
synthesis makes proteins. http://ghr.nlm.nih.gov/handbook/illustrations/proteinsyn
2. In a given gene, what kind of DNA mutation would not change the protein that is made?
A silent mutation does not change the protein, because numerous genetic codon can
code for the same amino acid. http://biology.about.com/od/basicgenetics/ss/genemutation.htm
3. What makes some amino acids hydrophobic and others hydrophilic? Some amino acids
may be hydrophobic and hydrophilic because some of the charged amino acids could
repel the water (polar/charged) and others may not repel the water.
http://www.proteinstructures.com/Structure/Structure/amino-acids.html
4. How common are mutations in the human genome? Is it very likely or very unlikely that
your DNA carries any mutations? It mostly depends on if your mom or dad carries any
mutation which is when it can be inherited to their offspring, which is when inherited
diseases are formed. In my family it is likely that I have a mutation in my DNA, since my
mom has a disease and that disease could be hereditary.
http://www.yourgenome.org/dgg/general/var/var_3.shtml
PROCESS
Determining how a gene is mutated
2a. this entry tells me that cystic fibrosis is a common genetic disease effecting 1 in 2500
Caucasian newborns. The chloride channels in cystic fibrosis are different because the
mutations in CFTR cause the chloride channel to not function right. It affects the body
because the mucus clogs the airway causing the person to have symptoms of cystic
fibrosis
2b.
i. The symptoms of cystic fibrosis include damage to the respiratory system and
chronic digestive problems. The symptoms with cystic fibrosis can also lead to diarrhea,
malnutrition, poor growth, and weight loss.
ii. The gene(s) that is mutated in cystic fibrosis is CFTR.
4
a. The ABC (ATP-binding cassette transporters) is the family of genes that CFTR
belong to. The ATP is also a family that the CFTR gene belongs too.
b. CFTR is located on chromosome 7.
c. The amino acid that is mutated would be the amino acid at position 508 in the
protein of CFTR.
5
a. The family usually carries water in and out of the cell.
b. All genes in a family all have similar sequences of DNA building blocks which would
be nucleotides.
From DNA to Amino Acids
1.
Transcript
Mutation
1408G>A
1516A>G
4002A>G
rsID
rs213950
rs1800091
N/A
Codon
Sequence
Change
(DNA)
GTG →
ATG
ATC →
GTC
CCA →
CCG
Codon
Sequence
Change
(mRNA)
GUG →
AUG
AUG→
GUG
CCA →
CCG
Amino
Acid
Sequence
Change
V [Val]
→
M [Met]
M[Met]
→
V[Val]
P[Pro] →
P[Pro]
Effect
Pathogenic
or NonPathogenic
Changes
from a
neutral,
nonpolar
amino acid to
another
neutral,
nonpolar
amino acid.
NonPathogenic
Changes
form a
nonpolar
amino acid,
to another
nonpolar
amino acid
NonPathogenic
Changes
from a polar,
uncharged
amino acid,
to another
polar,
uncharged
amino acid
NonPathogenic
2694T>G
4521G>A
328G>C
1079C>A
3484C>T
N/A
N/A
rs113993958
rs75053309
rs74767530
ACT →
ACG
CAG →
CAA
GAC →
CTG
CAT →
GTA
CGA →
GCT
ACU→
ACG
CAG →
CAA
CAG →
CUG
CAU →
GUA
CGA →
GCU
T[Thr] →
T[Thr]
Changes
from a polar,
uncharged
amino acid,
to another
polar,
uncharged
amino acid
NonPathogenic
G[Gln]
→
G[Gln]
Changes
from a polar,
uncharged
amino acid,
to another
polar,
uncharged
amino acid
NonPathogenic
G[Gln]
→
L[Leu]
It changes
from a polar,
uncharged
amino acid to
a nonpolar
amino acid
Pathogenic
H[His]
→
V[Val]
It changes
from a
positively
charged
amino acid to
a nonpolar
amino acid
Pathogenic
A[Arg]
→
A[Ala]
It changes
from a
positively
charged
amino acid to
a nonpolar
amino acid
Pathogenic
314026A>A
3659C>T
271G>A
19G>T
1572C>A
350G>A
rs76151804
rs1800123
rs121908750
rs121909045
rs121908754
rs78655421
ATG →
TAC
CAG →
GTC
GGG→
CCC
GAA →
CTT
CCA →
GGT
GCT →
CGA
AUG →
UAC
CAG →
GUC
GGG →
CCC
GAA →
CUU
CCA →
GGU
GCU →
CGA
M[Met]
→
T[Tyr]
It changes
from a
nonpolar
amino acid to
an aromatic
amino acid
Pathogenic
G[Gln]
→
V[Val]
It changes
from a polar,
uncharged
amino acid to
a nonpolar
amino acid
Pathogenic
G[Gln]
→
P[Pro]
Changes
from a polar,
uncharged
amino acid,
to another
polar,
uncharged
amino acid
Pathogenic
G[Glu]
→
L[Leu]
I changed
from a
negatively
charged
amino acid to
a nonpolar
amino acid
Pathogenic
P[Pro] →
G[Gly]
It changes
from a polar,
uncharged
amino acid to
a nonpolar
amino acid
Pathogenic
A[Ala]
→
A[Arg]
It changed
from a
nonpolar
amino acid to
a positively
charged
amino acid
Pathogenic
2834C>T
rs397508442
CGA →
GCT
CGA →
GCU
A[Arg]
→
A[Ala]
It changed
from a
positively
charged
amino acid to
a nonpolar
amino acid
Pathogenic
4
b. A Silent Mutation does not cause the amino acid sequence to change.
i. Yes, numerous amounts of the non-pathogenic alleles have such a mutation.
c.
ii. The mutation would equal into a frame shift mutation, since if you add another
nucleotide it would result in a frame shift.
Testing How the Mutation Matters
3
b. If the protein cannot fold up into its correct shape then the protein would not
be able to carry out its original function.
c. The non-pathogenic do not disrupt the protein function because a silent
mutation usually occurs in these types of alleles and those types of mutations do not disrupt the
proteins functions.