1. Introduction to Human Genetics
Chapter One

2. What is DNA? Deoxyribonucleic Acid: String of nucleotides deoxyribose
Nucleotides made up of three parts:
deoxyribose
(a sugar) OH
HO-CH2 +
P – – = O -
phosphate +
cyclic amine
(base) N

3. Nucleotide OH
O-CH2
P – – = O - N

4. DNA Specific Bases Sugar-Phosphate Backbone (negatively charged) N - O
O-CH2
P – – = O - N
Specific Bases
O-CH2
P – – = O - N O
O-CH2
P – – = - N
Sugar-Phosphate
Backbone
(negatively charged)

5. The Five Bases A = Adenine T = Thymine G = Guanine C = Cytosine
RNA only:
U = Uracil (replaces T)

7. Structures of Bases Pyrimidines T U C Purines A G O NH2 O CH3 N N N O

10. DNA T A Sequence of DNA is order of the bases attached to backbone C -
P – – = O - T -
O-CH2
P – – = O A -
O-CH2
Sequence of DNA
is order of the bases
attached to backbone
P – – = O C - O
O-CH2

11. Double Helix Sugar-Phosphate backbone is on outside
Bases are inside - Hydrogen-bonding to opposing base on opposite strand
Forming Base Pairs

12. Base Pairing Experiments showed: Therefore…
Two strands were always same distance apart
Percentages of A always matched T, and G always matched C
Therefore…
A Purine must always be base paired to a Pyrimidine
A = T, and G = C
Strands must be complementary =

14. 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) =

15. 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.
An authoritative principle, belief, or statement
of ideas or opinion, especially one considered to be
absolutely true.

16. Central Dogma
DNA
RNA
Protein
Transcription
Translation

17. Transcription initiation elongation termination RNA polymerase
Double Stranded DNA
“Promoter” opens
initiation
elongation
termination
single stranded mRNA

18. Translation 4 Nucleotides 20 amino acids
...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 = 4 possible amino acids .
2 base codon = 16 possible amino acids
3 base codon = 64 possible amino acids

19. Translation
amino acid
tRNA
single stranded mRNA }
Codon (3 bases)

20. The Genetic Code UUU UUC UUA UUG CUU CUC CUA CUG AUU AUC AUA AUG GUU
GUC
GUA
GUG
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
ACU
ACC
ACA
ACG
GCU
GCC
GCA
GCG
UAU
UAC
UAA
UAG
CAU
CAC
CAA
CAG
AAU
AAC
AAA
AAG
GAU
GAC
GAA
GAG
UGU
UGC
UGA
UGG
CGU
CGC
CGA
CGG
AGU
AGC
AGA
AGG
GGU
GGC
GGA
GGG
Phe
Leu
Val
Ser
Pro
Thr
Ala
Tyr
Stop
His
Gln
Asn
Lys
Asp
Glu
Cys
Arg
Ser
Gly
Stop
Trp
Ile
Met

21. Translation
Note: Actually a different tRNA for each different codon

22. Proteins Sequence Structure Function
Protein Sequence = order of the amino acids
Sequence
Structure
Function

23. 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

24. 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

25. Gene Structure
mRNA
protein

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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
Ask class what are examples of genetic (gender, fingerprints) vs. non-genetic traits (racism)?

32. 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

33. 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

34. Genotype vs. Phenotype
Genotype = combination of alleles individual is carrying
Genes (which versions)
Phenotype = measurable traits individual shows
Final Product

35. Applications: Selection Evolution Forensics Medical Care
First use of genetics
What are some examples?
Evolution
Tracing origins
Forensics
Medical Care
Studying, treating, curing diseases

36. Next Class: Read Chapter Three Homework – Chapter One Problems;
Review: 1, 2, 4
Applied: 3, 4, 11, 14