Download Chapter One

Introduction to Human
Genetics
Chapter One
What is DNA?
• Deoxyribonucleic Acid:
– String of nucleotides
• Nucleotides made up of three parts:
OH
ON
–
HO-CH2
-O
–
+
P – O-
=
+
O
N
OH
deoxyribose
(a sugar)
phosphate
cyclic amine
(base)
Nucleotide
N
–
O-
–
P – O-CH2
=
O
OH
-O
N
O-
–
DNA
N
–
-O P – O-CH2
N
=
Specific Bases
O
N
–
O
–
-O P – O-CH2
N
=
O
–
O
–
-O P – O-CH2
=
O
O
Sugar-Phosphate
Backbone
(negatively charged)
N
N
The Five Bases
•
•
•
•
A = Adenine
T = Thymine
G = Guanine
C = Cytosine
• RNA only:
– U = Uracil (replaces T)
Structures of Bases
Pyrimidines
O
NH2
O
CH3
N
N
N
N
N
N
T
U
C
NH2
Purines
O
N
N
N
N
N
N
A
NH2
N
N
G
O-
–
DNA
T
–
-O P – O-CH2
=
O
–
O
A
–
-O P – O-CH2
=
O
–
O
–
-O P – O-CH2
=
O
O
Sequence of DNA
is order of the bases
attached to backbone
C
Double Helix
• Sugar-Phosphate backbone is on outside
• Bases are inside - Hydrogen-bonding to
opposing base on opposite strand
• Forming Base Pairs
Base Pairing
•
Experiments showed:
1. Two strands were always same distance
apart
2. Percentages of A always matched T, and G
always matched C
•
Therefore…
1. A Purine must always be base paired to a
Pyrimidine
2. A = T, and G == C
3. Strands must be complementary
Summary of DNA
• String of Nucleotides
• deoxyribose Sugar-Phosphate backbone
• 4 Bases:
– A, G are Pyrimidines
– T, C are Purines
–A=T
–G=
=C
• Two complementary strands (double helix)
Central Dogma
dog·ma
P Pronunciation Key (dôg ma)
n. pl. dog·mas or dog·ma·ta
1. A doctrine or a corpus of doctrines relating to
matters such as morality and faith, set forth in an
authoritative manner by a church.
2. An authoritative principle, belief, or statement
of ideas or opinion, especially one considered to be
absolutely true.
Central Dogma
DNA
Transcription
RNA
Translation
Protein
Transcription
RNA polymerase
Double Stranded DNA
“Promoter” opens
initiation
elongation
termination
single stranded mRNA
Translation
...AGAGCGGAATGGCAGAGTGGCTAAGCATGTCGTGATCGAATAAA...
AGAGCGGA.AUG.GCA.GAG.UGG.CUA.AGC.AUG.UCG.UGA.UCGAAUAAA
MET.ALA.GLU.TRP.LEU.SER.MET.SER.STOP
4 Nucleotides
20 amino acids
1 base codon - 41 = 4 possible amino acids
2 base codon - 42 = 16 possible amino acids
3 base codon - 43 = 64 possible amino acids
Translation
amino acid
tRNA
single stranded mRNA
}
Codon (3 bases)
The Genetic Code
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
AUU
AUC
AUA
AUG
GUU
GUC
GUA
GUG
Phe
Leu
Leu
Ile
Met
Val
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
ACU
ACC
ACA
ACG
GCU
GCC
GCA
GCG
Ser
Pro
Thr
Ala
UAU
UAC
UAA
UAG
CAU
CAC
CAA
CAG
AAU
AAC
AAA
AAG
GAU
GAC
GAA
GAG
Tyr
Stop
His
Gln
Asn
Lys
Asp
Glu
UGU
Cys
UGC
UGA Stop
UGG Trp
CGU
CGC
Arg
CGA
CGG
AGU
Ser
AGC
AGA
Arg
AGG
GGU
GGC
Gly
GGA
GGG
Translation
Note: Actually a different tRNA for each different codon
Proteins
• Protein Sequence = order of the amino
acids
Sequence
Structure
Function
Central Dogma Summary
•
•
•
•
•
•
DNA is in the nucleus of each cell
DNA encodes for RNA (transcription)
RNA encodes for Proteins (translation)
DNA and RNA are made of nucleotides
Protein is made of amino acids
A protein’s function is determined by it’s
structure, which is determined by it’s
sequence
• Therefore…DNA encodes protein function
What is a gene anyway?
• A gene is a small piece of DNA
• It begins with a promoter
– This is region of sequence that tells RNA
polymerase “start here”
– Also regulates amount of mRNA that is made
• Includes Introns and Exons
– Introns are removed during transcription
– Exons are the parts of the sequence that
become mRNA
• Also, gene has regulatory regions
Gene Structure
mRNA
protein
One gene = one protein
• Only not really:
– Splice variants = form different proteins
– Different alleles = different versions of
the same protein
– Polymorphisms; may change protein
sequence or regulation of protein
– Mutations may destroy a protein, or
change it’s normal function or
expression
Genetic variance:
• Allele: Alternative form of one gene, usually form
same protein, with slight changes, but same
function
• Polymorphism: Usually a silent change
(something that doesn’t affect the protein), that
is often common in population
• Mutation: A change in the DNA sequence that
will change the protein’s function or regulation,
usually in a detrimental way
Sequence vs. Expression
• Genetic variances can affect:
– Sequence of the gene
• May change the sequence of the protein
• May be “silent”
– Level the gene is expressed
• Amount of protein that will be made
– Where a gene is expressed
• What cell type
• What tissue
• What time point in development
Chromosomes
• Chromosomes can carry thousands of
genes
– Made of DNA and proteins
• Human have 22 pairs of autosomal
chromosomes
– 1 is the largest, 22 is the smallest
• Humans have 1 pair of sex chromosomes
– XY is male, XX is female
– X inactivation in females
How are genes inherited?
• Genes are carried in the DNA
• DNA is condensed into chromosomes
• Each individual has two copies of every
chromosome
• Sex cells (sperm or eggs) each have one
copy of every chromosome
• Mating leads to one copy of every
chromosome coming from one parent and
other copy coming from the other parent
– Variances are mixed in offspring
Traits
• Any distinguishing feature that can be
measured
– Quantitatively (ex. height, weight)
– Qualitatively (ex. disease status)
• Inherited Traits
– Completely genetic
• Non-inherited Traits
– Completely Environmental
• Complex Traits
– Partially Genetic, partially environmental
Complex Traits
• Disorder that is proven heritable, yet has
no clear mode of inheritance
– Doesn’t follow Mendel’s laws
• More than one gene
• Interaction between genes
• Interaction between gene(s) and
environment
Why Common Complex Disorders
and Rare Mendelian Disorders?
• Evolution can act upon a single
detrimental gene
– negative selection
• Gene functions that are good for some
things, but can be harmful in excess
– ex: rational fear vs. anxiety disorders
• Normal alleles only predisposing
– other mutations/environment present
Genotype vs. Phenotype
• Genotype = combination of alleles
individual is carrying
– Genes (which versions)
• Phenotype = measurable traits individual
shows
– Final Product
Applications:
• Selection
– First use of genetics
– What are some examples?
• Evolution
– Tracing origins
• Forensics
– What are some examples?
• Medical Care
– Studying, treating, curing diseases
Next Class:
• Read Chapter Three
• Homework – Chapter One Problems;
– Review: 1, 2, 4
– Applied: 3, 4, 11, 14