Introduction to Human Genetics Chapter One. What is DNA? Deoxyribonucleic Acid: –String of...
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Transcript of Introduction to Human Genetics Chapter One. What is DNA? Deoxyribonucleic Acid: –String of...
Introduction to Human Genetics
Chapter One
What is DNA?
• Deoxyribonucleic Acid:– String of nucleotides
• Nucleotides made up of three parts:
deoxyribose(a sugar)
OH
OH
HO-CH2
+ P –
– =
–
O
O
O
O -
-
-
phosphate
+
cyclic amine(base)
N
N
NucleotideOH
O-CH2P –
–
=
–O
O
O
-
-
N
N
DNA
O-CH2P –
–
=
–
O
O
O
-
N
N
O
O-CH2P –
–
=
–
O
O
O
-
N
N
O-CH2P –
–
=–
O
O
O
-
-
N
N
Sugar-Phosphate Backbone
(negatively charged)
Specific Bases
The Five Bases
• A = Adenine
• T = Thymine
• G = Guanine
• C = Cytosine
• RNA only:– U = Uracil (replaces T)
Structures of Bases
N
N
Pyrimidines
N
N
N
N
Purines N
N
N
N
CH3O O
O O O
O
NH2
NH2
N
N
N
N
NH2
A G
T U C
DNA
O-CH2P –
–
=
–
O
O
O
-
O
O-CH2P –
–
=
–
O
O
O
-
O-CH2P –
–
=–
O
O
O
-
- T
A
C
Sequence of DNAis order of the basesattached to backbone
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
RNA
Protein
Transcription
Translation
TranscriptionRNA polymerase
Double Stranded DNA
“Promoter” opens
initiation
elongation
termination
single stranded mRNA
Translation
AGAGCGGA.AUG.GCA.GAG.UGG.CUA.AGC.AUG.UCG.UGA.UCGAAUAAA MET.ALA.GLU.TRP.LEU.SER.MET.SER.STOP
...AGAGCGGAATGGCAGAGTGGCTAAGCATGTCGTGATCGAATAAA...
1 base codon - 41 = 4 possible amino acids
2 base codon - 42 = 16 possible amino acids
3 base codon - 43 = 64 possible amino acids
4 Nucleotides 20 amino acids
Translation
single stranded mRNA
tRNAamino acid
Codon (3 bases)}
The Genetic CodePhe
Leu
Leu
Val
Ile
Met
Ser
Pro
Thr
Ala
Tyr
Stop
His
Gln
Asn
Lys
Asp
Glu
Cys
Arg
Ser
Arg
Gly
StopTrp
UUUUUCUUAUUG
CUUCUCCUACUG
AUUAUCAUAAUG
GUUGUCGUAGUG
UCUUCCUCAUCG
CCUCCCCCACCG
ACUACCACAACG
GCUGCCGCAGCG
UAUUACUAAUAG
CAUCACCAACAG
AAUAACAAAAAG
GAUGACGAAGAG
UGUUGCUGAUGG
CGUCGCCGACGG
AGUAGCAGAAGG
GGUGGCGGAGGG
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