Genetics is the study of genes, inheritance patterns, and genetic variation among organisms.
Can affect diseases and mortality
o i.e. Cancer progression can be related to genetic makeup
5 different single nucleotide polymorphisms (changes); 5 different DNA changes
within different genes that can lead to aggressive prostate cancer
A brief history of genetics…
Ex ovo Omnia (all from the egg)
o William Harvey - 1651
o Epigenesis: substances present in egg differentiate into adult structures
1694: Nicholas Hartsoeker
Each sperm thought to contain a miniature adult
o All structures were present and creature just got larger
Female was “dirt” for sperm to grow
1830: Theodor Schwann/Matthias Schleiden
Organisms are made of cells
Darwin, Wallace, & Evolution
Natural selection: based on observation that populations consist of more individuals than can be
Those w/ heritable traits that enhance survival persist.
A theory without a mechanism until…
Experimented w/ pea plants in the monastery garden 1856 – 1863; published his studies in 1866
Determined that flower color (purple vs. white) and other traits were controlled by genes that
occur as pairs
o Observed that traits segregated in his experiments and concluded that they occur as pairs
that could be separated during the act of reproduction
Chromosomal Theory of Inheritance
Walter Sutton and Theodor Boveri (early 1900‟s)
Proposed that heritable features (genes) are carried on chromosomes
Eukaryotes are generally diploid (2n)
This means that 1 copy of each chromosome is received from each parent.
Karyotype: set of chromosomes within a eukaryotic cell
Chromosomes are copied
Mitosis: replicating cells
Meiosis: making gametes A fertilized human egg has how many chromosomes?
C) 23 * if unfertilized
D) 46 *
Structure of DNA
Structure described in 1953 by Watson & Crick
G: Guanine, A: Adenine, T: Thymine, C: Cytosine
DNA is made up of complimentary strands that wrap around each other to form a double helix
What are genes made of?
Initial debate: Protein or DNA?
Chromosomes are composed of both!
Read C1: debate of protein vs. DNA
What is a Gene?
A unit of heredity that consists of a stretch of DNA that codes for protein or RNA chain that has
(segment of DNA that does something)
Alleles are different variants of a gene.
A single gene can likely have multiple alleles.
Genotype vs. Phenotype
Genotype: alleles (DNA sequences) that control a trait
Phenotype: observable features of an organism
o i.e. thumb crossing
o different phenotypes result from different genotypes
First Described fly mutant
Thomas Hunt Morgan, 1910
Red is fly‟s natural eye color
White is a mutant color
Why studying model organisms is important
Gene affected in white fly mutant encodes a membrane protein that transports red pigment
This protein is related to CFTR protein that is affected in cystic fibrosis (CFTR is an ion channel
that transports chloride) 8/28/13
Model organisms used to study genetics.
Why is understanding genetics important?
Personalized medicine ie. pharmacogenetics: how does genetic variation impact a patient‟s
Commercial testing developed to detect variations in the gene (CYP2C9) that metabolizes
warfarin (coumadin), an anti-coagulant used to prevent blood clots
Chapter 2: Mitosis & Meiosis
Transfer of genetic material
Mitosis: from cell to daughter cells
Meiosis: from parent to offspring
Chromosomes: a metaphase preparation and resulting karyotype
Homologous chromosomes: one from dad & one from mom
Sister chromatids: duplicated set that will later separate
Centromere: condensed part of chromosome where sister chromatids are attached; placement is
how chromosomes are classified
Interphase (non-mitosis parts)= G1 + S (DNA synthesis) + G2 (cytoplasm has already doubled by
o Intense metabolic activity for growth of cell
o DNA replication occurs prior to mitosis
o Chromosomes have duplicated during S phase but are not condensed in Interphase
Mitosis refers to the point where chromosomes are being distributed between the two daughter
DNA Synthesis occurs during mitosis. F
Associated w/ spindle fibers used in mitosis and meiosis
Differentiated regions in cell (centrosomes) house pairs of centrioles
o These organize the microtubules of spindle fibers to be able to pull the chromosomes
Microtubule arrays that attach to and move chromosomes during cell division (pull apart sister
Centrioles migrate to opposite sides of cell
o where they locate to controls the plain of division
Centrioles organize microtubules into spindle fibers that establish axis for chromosome
Nuclear envelope disappears
Chromosomes migrate to equatorial plane (=metaphase plate)
Kinetochore forms (protein complex that attaches centromeres to spindle fibers)
End of Metaphase
Chromosomes are all lined up along metaphase plate
Sister chromatids separate from one another and migrate to opposite poles
Separated sisters = “daughter chromosomes”
Telophase & Cytokinesis
Cytoplasm is divided among the two daughter cells
Nuclear envelope reforms
Spindle fibers disappear
Read how process of mitosis is different for plant cells.
Transfer of genetic material
Mitosis duplicate and distribute (2n to
Functions of Meiosis
Allows haploid gametes to combine at fertilization so that genome size is maintained at 2n
o If this doesn‟t happen properly, disorders can occur
Ie. Down syndrome ( trisomy 21 – 3 copies of chromosome 21)
Introduces GENETIC VARIATION
o Unique combinations of parental chromosomes found in gametes
o Crossing over (= genetic exchange) between homologous chromosomes pairs results in
17 (Chapter 2) A diploid cell has 3 pairs of homologous chromosomes, each heterozygous (C1,
C2; M1, M2; S1 S2).
Q – what chromosome combinations could be present in haploid cells after meiosis?
20. Organism with n=10 (2n=20). What is the probability that a sperm will have all 10 maternal
The probability of getting a maternal chromosome for C1 = 0.5 (50%). What about for maternal
(Example of 2 pairs of homologous chromosomes
Homologous chromosomes pair up (=synapsis) and crossing over occurs between non-sister
chromatids (in reality, it is both pairs unlike the figure)
Tetrad of 4 chromatids
Meiosis 1: tetrads to dyads
Meiosis 2: dyads to monads 8/30/13
20. Organism w/ n=10 (2n=20). What is the probability that a sperm will have all 10 maternal
The probability of getting a maternal chromosomes for C1 = 0.5 (50%). What about for maternal
C1 – C10?
Answer: 0.5 ^ 10
Cell structure & genetic function
Eukaryotes have chromosomes in membrane structure
o Nucleolus – region where rRNA is synthesized
Complexes of proteins and RNAs
Site where mRNA are translated into proteins
Free in cytosol
Associated w/ ER
Prokaryotes have DNA (as one circular chromosome) just in the cell
o No membrane bound organelles
o Nucleoid – area where DNA is compacted
Found in plant and animal cells
Site of oxidative respiration
Found in plant algal, protozoan cells
Produces energy through photosynthesis
Chloroplast and Mitochondrial DNA
Each has its own genome separate from chromosomes in nucleus
Duplicate themselves, transcription & translation separate from the nucleus
Mitochondrial DNA entirely maternally inherited
Chloroplast DNA generally maternally inherited
Who ingerited great-grandma‟s mitochondrial genome?
o 1) D-F, G, L
o 2) D –F, G –L
o 3) A – C, G – I
o 4) D – F, J – L
o 5) B, D – F, G, L
Mendelian Genetics Gregor Johann Mendel
No knowledge of chromosomes or meiosis
Determined that units of inheritance exist
Was able to predict the behavior of these units: i.e. he was able to anticipate the results of his
Mendel followed 7 traits.
Each trait had 2 contrasting forms for these particular traits
Was able to obtain true breeding strains: plants that when self – fertilized produced offspring
showing the same form of a particular trait (i.e. all offspring had purple flowers)
Monohybrid crosses of true-breeding individuals differing in only one trait revealed how that
trait is transmitted from generation to generation
One of Mendel‟s monohybrid crosses…
F1 plants = 100% yellow
o Therefore: yellow is dominant over green
F2 plants = 75% yellow 25% green
o (3:1 ratio)
Results of Mendel‟s monohybrid crosses:
F1 offspring identical to one parent
But 3:1 ratios observed in F2 generation
Mendel tried his crosses in both directions: the results were not affected by which parent
carried a particular form of a trait.
o Sometimes that is not the case in more complicated genetics
For example, the yellow form of seed color always dominated the green form in the F1.
Proposed that unit factors (=genes) pass unchanged from one generation to the next and
determine the traits expressed. Individuals have a pair (=2 alleles) of each unit factor.
One of the unit factors in a pair dominates the other, which is recessive.
The two unit factors segregate randomly during gamete formation.
Wrinkled vs. round
The mutant gene affects a protein involved in starch synthesis
o the defect in starch synthesis and if loss of water gives them wrinkled appearance
DD x dd parents monohybrid cross
Result: all F1 Dd heterozygous offspring are tall.
Dd x Dd F1 self-fertilized monohybrid cross
Results: F2 offspring are tall and short
Genotypic ratio: 1:2:1
Phenotypic ratio: 3:1
Test crosses: can deduce an individual‟s genotype by crossing it to a recessive homozygote. The traits that Mendel studied segregate independently.
If genes are considered to be linked, they are inherited together. If they are close to each other on the
same chromosome, then Mendel‟s rule is not followed. They won‟t segregate independently. The traits
that he studied were far enough away on the same chromosome or on different chromosomes.
Read Chi – square Test and monohybrid and dihybrid tests
1000 F2 plants
X^2 = sum (o-e)^2/e
Number (n) of categories (3,1) in monohybrid cross = 2 therefore degrees of freedom (n-1) = 1 9/4/13
P = 0.48 can be thought of as a 48% probability that similar variation would appear again due to chance.
If p less than or equal to 0.05, reject null hypothesis
# 18 and 19 (Chapter 3)
How can you tell that this pedigree depicts an autosomal recessive trait?
Recessive traits typically skip generations.
Either 1-3 or 1-4 must be heterozygous.
2-1 and 2-2 are carriers.
Recessive autosomal traits appear equally in both sexes.
Questions: how would this pedigree be drawn to show an affected individual in generation III
who died from Tay–sachs disease? Do affected individuals reproduce?
Read Tay-sachs on p 48
How can you tell that this pedigree depicts an autosomal dominant trait?
Dominant traits almost always appear in each generation.
Affected individuals all have an affected parent.
Dominant autosomal traits appear equally in both sexes.
Anyone with an affected parent has a 50 % chance that they do inherit the affected allele.
1-1is heterozygous for a dominant allele.
Ie. Huntington‟s disease
o Appears generally middle age after they have reproduced
o Neurogenitive disorder
Affects muscle and other functions
Ie. Familial hypercholesterolemia
o Affects LDL receptors
o If heterozygous, you can have heart heart in 40s or younger
o If homozygous, you can have heart attack before five and usually will before 20
Chapter 4: Modifications of Mendelian Inheritance
An exception to independent assortment
Genes that occur on the same chromosome in close proximity will exhibit linkage. Alleles will
be more likely to be inherited together than separate.
Heterogametic sex (e.g. human males XY) only have one copy of X chromosome.
Early example: inheritance of white (w) in Drosophilia*.
Segregation ratios not the same as normal monohybrid cross
o can be different than that of autosomal
Males are hemizygous (only have one copy of a gene): lack white locus on Y chromosome
X- linked inheritance in flies
All daughters are red-eyed heterozygotes
All sons are white-eyed hemizygotes X-linked diseases
Also Duchenne muscular dystrophy, hemophilia
Color blindness is X–linked recessive
X-linked dominant disease
Trait never passed from father to son
All daughters of an affected male are affected
Wild-type = allele that occurs most frequently in a population
Mutation is the source of new alleles. It can affect a characteristic of an organism because it can affect the
function of an encoded protein.
There can be multiple alleles for a particular gene (not just 2).
More than 100 alleles of the white locus!
Types of mutations
Loss-of-function: allele that results in reduction or elimination of the functional activity of the
protein or RNA encoded by the affected gene (total elimination = null allele)
o Ie. If protein was enzyme that bound to a substrate, the mutation affected the part of the
protein that binds to the substrate to where it cannot bind
Gain-of-function: allele that results in increased expression or activity or ectopic (activity is
present when it shouldn‟t be) activity of the affected gene product
o Ie. Mutation can cause inappropriate expression and affect when protein is present during
development (such as transcription factor) in different tissue or different times
Neutral: allele that does not detectably change the function of the gene affected
o Ie. triplet changed still encodes same amino acid or new amino acid is similar enough to
old amino acid that there is no real change in protein
Snapdragons; neither R1 nor R2 allele is dominant
F2 ratio= 1 R1R1: 2 R1R2: 1 R2R2 9/6/13
When 2 alleles of a single gene express distinct, detectable proteins
Ie. M and N forms of a gl