Introduction to Advanced Genetics: 2
Definition of Genetics 2
Organization of DNA into Chromosomes 2
Important Terms 3
DNA (deoxyribonucleic acid) 4
Discovery 4
Cell Cycle: 5
Interphase 5
M phase / Mitotic stage 6
Mitosis 6
Cytokinesis 6
Meiosis 7
Population Genetics 8
Definition 8
Importance: 9
How did Population Genetics start? 9
Hardy-Weinberg Principle 9
Formulas 10
1. Two Alleles (p & q) 10
a. Allelic Frequency 10
b. Genotypic Frequency 10
2. Multiple Alleles (p, q & r) 10
a. Allelic Frequency 10
b. Genotypic Frequency 10
LOD Score 10
Definition: 10
Formulas 11
1. Phase Known 11
2. Phase Unknown 11
Practice Test: Population Genetics 11
6, 8, 10 11
21. 1 11
21.2 12
21.3 12
23.1, 23.3, 23.5 13
Answers of Population Genetics (Essentials of Genetics) 13
Answers of Population Genetics (Principles of Genetics) 14
Practice Test: LOD score 14
1. Problem 1 14
2. Problem 2 15
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3. Problem 3 15
4. Problem 4 15
Answers of LOD Score (from youtube) 15
1. Answer 1 15
2. Answer 2 16
3. Answer 3 16
4. Answer 4 16
Introduction to Advanced Genetics:
Definition of Genetics
● The study of how genes and how traits are passed down from one generation to
the next.
- Gregor Mendel (known to be the father of Genetics) is famous for discovering
“particulate inheritance” or the idea that hereditary elements are passed on in
discrete units rather than “blended” together at each new generation when he
experimented on garden pea hybrids. Today we call those discrete units
genes. A gene is a hereditary factor that determines (or influences) a
particular trait.
Organization of DNA into Chromosomes
2
Important Terms
1. DNA (deoxyribonucleic acid) is the genetic material of living organisms. It
provides the instructions to cells of the body (for humans or eukaryotes). These
instructions for the cells include growing, functioning and responding to the
environment. In plant cells, a great amount of DNA is found in the nucleus, called
nucleus DNA. Mitochondria and chloroplasts contain their own DNA as well
called Mitochondrial DNA and chloroplasts DNA, respectively.
2. Histones - a group of basic proteins that provide structural support and compact
shape of chromosomes.
3. Nucleosome - small length/section of DNA wrapped around eight histone
proteins.
4. Chromatin - thread of nucleosome; whole structure of complex DNA and
proteins.
5. Chromosome - threadlike structure made of protein and a single molecule of
DNA that serve to carry the genomic information from cell to cell. It is passed
from parents to offspring.
6. Genome - organisms’ complete set of DNA; it is all the genetic material in an
organism.
- Responsible for expressions of traits
- Human Genome: Nucleus DNA (all 23 pairs of chromosomes in the
nucleus)+Mitochondrial DNA.
- Gene vs. Genome: a gene is a specific segment of DNA that tells the cell
how to function. A genome is the entirety of the genetic material inside an
organism. The Human Genome consists of between 20,000 and 25,000
genes.
7. DNA Packaging - process of folding of an organism’s DNA into a compact
structure that can fit within the nucleus of a cell. Hence, it needs to be tightly
packed. It involves the process of DNA coiling.
- Histones are positively charged proteins, DNA is negatively charged (due
to its phosphate groups in its phosphate-sugar backbone). Thus, positively
charged histones proteins bind to negatively charge DNA very tightly.
8. DNA Coiling - process in organization of DNA into chromosomes where the DNA
wraps itself around a group of eight histone proteins to form a structure called
nucleosome. These nucleosomes can coil up tightly to form another structure
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called chromatin, the chromatin itself can condensely wrap up further to form the
chromosome structure.
9. Alleles - specific form or variation of a gene that can differ by one or more
nucleotides.
- Responsible for the variation in which a trait can be expressed.
- Example: Gene (code for height) Allele (tall or short).
- Example: Gene (eye color) Allele (blue, black, brown).
DNA (deoxyribonucleic acid)
Discovery
● Johann Friedrich Miescher’s Discovery of Nuclein: It all started humbly enough in
1869, when Swiss chemist Miescher found a phosphorus-containing substance
in white blood cells unlike the proteins he expected to find. He called this
substance a nuclein. Later, it became known as nucleic acid.
● Phoebus Levene’s Role in DNA’s Discovery: Fifty years later, in 1919,
Russian-born biochemist Levene characterized nucleic acids as molecules made
of phosphate, sugar, and four nitrogenous bases—adenine (A), guanine (G),
cytosine (C), and thymine (T). Levene also differentiated the deoxyribonucleic
acid (DNA) from the related genetic material ribonucleic acid (RNA).
● Oswald Avery, Colin MacLeod, and Maclyn McCarty Uncover DNA’s Genetic
Role: By 1944, Avery, MacLeod, and McCarty, at the Rockefeller Institute in New
York, showed that DNA—not proteins, as others had previously assumed—was
the substance that passed along genetic information in experiments involving
bacterial transformation.
● Rosalind Franklin, Maurice Wilkins, and Raymond Gosling on X-ray Diffraction:
Studies of DNA's structure through X-ray diffraction, by Maurice Wilkins and
Raymond Gosling, began in 1946. Rosalind Franklin’s expertise was then
brought to the team, where she contributed pivotal images of crystallized DNA
and crystallographic calculations. These images were critical to solving the
mystery of DNA's double helix structure.
● Erwin Chargaff and DNA’s Chemical Rules: In 1950, Chargaff published a paper
outlining the chemical rules for how nucleotide bases pair—that adenine always
pairs with thymine, and cytosine pairs with guanine. These paired bases are part
of the DNA structure.
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● James Watson, Francis Crick, and DNA’s Double Helix Structure: Watson and
Crick's quest to discover the structure of DNA began with their first meeting in the
summer of 1951. The model they initially proposed was wrong, featuring three
strands of DNA instead of two. The turning point came when they gained access
to Rosalind Franklin's work.
- In 1953, Watson and Crick published their findings on the structure of DNA
in a paper titled “A Structure for Deoxyribose Nucleic Acid.” Accompanying
Watson and Crick’s paper in the journal Nature were two additional articles
on DNA’s structure: one by Maurice Wilkins and one by Rosalind Franklin
and her colleague Raymond Gosling. Together, their findings
fundamentally changed how scientists (and eventually everyone) thought
about how the DNA molecule worked in heredity.
- The Nobel Prize: While the breakthrough discovery of DNA’s famous
double helix structure is often credited to Watson and Crick, they relied
extensively on the important DNA research conducted by many others
over many years.
- In 1962, Watson and Crick were awarded the Nobel Prize, together with
Maurice Wilkins, for the discovery of DNA's structure. Rosalind Franklin,
who had died four years before, was not included in the Nobel Prize, as a
Nobel Prize can only be shared by three living scientists.
● The Significance of the Discovery of DNA's Structure: The DNA double helix is
the most well-known molecular structure in all of biology. It gave an explanation
for how DNA is replicated when a cell divides, how it is inherited from generation
to generation, and how such an elementary molecule could provide all the
incredible complexity displayed by life on Earth.
● The discovery of DNA and its structure is considered one of the most important
scientific discoveries in modern times, leading to the development of modern
molecular biology and genomics.
https://www.ancestry.com/c/dna-learning-hub/dna-discovery
Cell Cycle:
● Cell cycle has different stages called G1, S, G2, and M.
● Total Human cell cycle is equivalent to 24 hours: G1 phase ( approx. 11 hrs), S
phase (approx. 8 hrs), G2 phase (approx. 4 hrs) and M phase (approx. 1 hr).
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● Definition: It is a series of events that takes place in a cell as it grows and divides
(cells replicate and make two new cells). A cell spends most of its time in what is
called interphase, and during this time it grows, replicates its chromosomes and
prepares for cell division. The cell then leaves interphase, undergoes mitosis and
completes its division. The resulting cells known as daughter cells, each enter
their own interphase and begin a new round of cell cycle.
Interphase
● Cells grow and make a copy of its DNA.
● The G1, S, and G2 phases together are known as interphase. The prefix inter-
means between, reflecting that interphase takes place between one mitotic (M)
phase and the next.
1. G1 phase. During G1 phase, also called the first gap phase, the cell grows
physically larger, copies organelles, and makes the molecular building blocks it
will need in later steps.
2. S phase. In the S phase, the cell synthesizes a complete copy of the DNA in
its nucleus. It also duplicates a microtubule-organizing structure called the
centrosome. The centrosomes help separate DNA during the M phase.
3. G2 phase. During the second gap phase, or G2 phase, the cell grows more,
makes proteins and organelles, and begins to reorganize its contents in
preparation for mitosis. G2 phase ends when mitosis begins.
M phase / Mitotic stage
During the mitotic (M) phase, the cell divides its copied DNA and cytoplasm to make two
new cells. Mitosis conserves the number of chromosomes from the parent cells. In
addition, it produces genetically identical daughter cells. M phase involves two distinct
division-related processes: mitosis and cytokinesis.
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Mitosis
In mitosis, the nuclear DNA of the cell condenses into visible chromosomes and is
pulled apart by the mitotic spindle, a specialized structure made out of microtubules.
Mitosis takes place in four stages: prophase (sometimes divided into early prophase
and prometaphase), metaphase, anaphase, and telophase.
Cytokinesis
In cytokinesis, the cytoplasm of the cell is split in two, making two new cells. Cytokinesis
usually begins just as mitosis is ending, with a little overlap. Importantly, cytokinesis
takes place differently in animal and plant cells.
Meiosis
It is a special type of cell division that creates sex cells/germ cells. It reduces the
number of chromosomes from the parent cells which is from diploid cells (2n=46) to
haploid (n=23). It consists of Meiosis I and Meiosis II.
Three events unique to meiosis occur during meiosis I:
1. Synapsis and crossing over. During prophase I, duplicated homologs pair up and
crossing over occurs, as described above. Synapsis and crossing over normally do not
occur during prophase of mitosis.
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2. Homologous pairs at the metaphase plate. At metaphase I of meiosis, chromosomes
are positioned at the metaphase plate as pairs of homologs, rather than individual
chromosomes, as in metaphase of mitosis.
3. Separation of homologs. At anaphase I of meiosis, the duplicated chromosomes of
each homologous pair move toward opposite poles, but the sister chromatids of each
duplicated chromosome remain attached. In anaphase of mitosis, by contrast, sister
chromatids separate.
Population Genetics
Definition
● Population Genetics is a discipline that studies genes in groups of individuals.
● Population genetics examines allelic variation among individuals, the
transmission of allelic variants from parents to offspring generation after
generation, and the temporal changes that occur in the genetic makeup of a
population because of systematic and random evolutionary forces.
● Studies the genetic makeup of groups of individuals and how a group’s genetic
composition changes with time.
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● Studies variation in alleles that naturally occurs among the genes within a
population.
● Linked to the study of Evolution, Natural selection, and Mendelian population.
● Studies how the gene pool of a population is measured.
Importance:
● Population geneticists investigate patterns of genetic variation within and among
groups of interbreeding individuals. Changes in genetic structure form the basis
for the evolution of a population. Thus, population genetics has become an
important subdiscipline of evolutionary biology.
How did Population Genetics start?
● Synthesis of Ronald Fisher, John Haldane, and Sewall Wright from all the
previous principles. – Mendelian Inheritance vs. Darwin’s Natural Selection.
● Studying genetics with a Mathematical approach.
● Each of these theorists developed formal models to explore how natural
selection, and other evolutionary forces such as mutation, would modify the
genetic composition of a Mendelian population over time.
Hardy-Weinberg Principle
● Formulated by Godfrey Harold Hardy, a German physician, and Wilhelm
Weinberg, a British mathematician, independently.
● Assumptions: If the population is large, randomly mating, and not affected by
mutation, migration, or natural selection, then:
- Prediction 1: The allelic frequencies of a population do not change;
- Prediction 2: The genotypic frequencies stabilize (will not change) after
one generation in the proportions 𝑝2 (the frequency of AA), 2pq (the
frequency of Aa), and 𝑞2 (the frequency of aa).
● The statement that genotypic frequencies stabilize after one generation means
that they may change in the first generation after random mating because one
generation of random mating is required to produce Hardy–Weinberg proportions
of the genotypes.
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● When genotypes are in the expected proportions of 𝑝2, 2pq, and 𝑞2, the
population is said to be in Hardy–Weinberg equilibrium.
● p2 + 2pq + q2 = 1
Formulas
1. Two Alleles (p & q)
a. Allelic Frequency
b. Genotypic Frequency
f(AA) = p2
f(Aa) = 2pq
f(aa) = q2
2. Multiple Alleles (p, q & r)
a. Allelic Frequency
b. Genotypic Frequency
3. If number of dominant allele and recessive allele is not given, use this formula;
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LOD Score
Definition:
● LOD Score or also known as the logarithm of the odds is devised by Newton E.
Morton in 1955.
● It is a statistical tool that is used to analyze linkage of human genes.
● LOD score is a representation of the likelihood of a linkage between two genetic
traits. If the score is high, it means that the traits are closely linked, and therefore
usually inherited together. Low scores, on the other hand, indicate a low linkage.
Formulas
1. Phase Known
2. Phase Unknown
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1- Essentials of Genetics 10th Edition Klug*
Practice Test: Population Genetics
21. 1
12
21.2
21.3
Example from book conservation and the genetics of population
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23.1, 23.3, 23.5 (Principles of Genetics)
Answers of Population Genetics (Essentials of Genetics)
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Answers of Population Genetics (Principles of Genetics)
*More problems chapter 23 principles of Genetics
Practice Test: LOD score
1. Problem 1
15
2. Problem 2
3. Problem 3
4. Problem 4
Answers of LOD Score (from youtube)
1. Answer 1
16
2. Answer 2
3. Answer 3
4. Answer 4
17
