Download Chapter 2. The beginnings of Genomic Biology – Classical Genetics

Chapter 2. The beginnings of Genomic Biology –
Classical Genetics
Contents
2. The beginnings of Genomic Biology – classical
genetics
2.1. Mendel & Darwin – traits are conditioned by genes
2.2. Genes are carried on chromosomes
2.3. The chromosomal theory of inheritance
2.4. Additional Complexity of Mendelian Inheritance
2.4.1. Multiple alleles
2.4.2. Incomplete dominance and co-dominance
2.4.3. Sex linked inheritance
2.4.4. Epistasis
2.4.5. Epigenetics
2.5. Genes on the Same Chromosome are Linked
2.5.1. Meiosis: chromosomes assort independently
2.5.2. Mapping genes on chromosomes
2.6. Quantitative Genetics: Traits that are Continuously Variable
2.7. Population Genetics: Traits in groups of individuals
 CHAPTER 2. THE BEGINNINGS OF GENOMIC
BIOLOGY –CLASSICAL GENETICS
It should be clear that the beginings of genomic
biology are grounded in classical or Mendelian Genetics.
Once the relationship between traits and genes was
understood, the relationship between cells and genetics
was investigated, leading to the discovery of
chromosomes, and a quest for the substance that
carried the genetic information began, culminating in
the discovery of DNA. These studies constitute the
contribution of classical genetics to the founding of the
genomic era.
CONCEPTS OF GENOMIC BIOLOGY
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2.1. MENDEL & DARWIN –
TRAITS ARE CONDITIONDBY GENES.
The idea of genomic biology begins with a
consideration of what makes up genomes.
Specifically what are genes. The timeline of genetics
and genomics begins with the early work of Charles
Darwin and Gregor Mendel who didn’t really talk
about genes per se, but who did describe the
behavior of the characteristics of biological
organisms, which they referred to as traits.
In 1859 Charles Darwin published his book On the
Origin of Species. In this work Darwin described a
mass of descriptive support for the concept that
“traits” are stably transmitted through subsequent
generations, and that organisms that have superior
traits survive their natural environment to pass those
traits on to the next generation. However, Darwin did
not describe any mechanism for such transmission of
traits to the next generation.
Experimental evidence for a mechanism explaining
how traits pass to subsequent generations came in
1866 when an Austrian monk, Gregor Mendel,
published his studies covering 10 years worth of work
on the mechanism of inheritance of 7 characteristics
in garden peas in a paper called “Experiments in Plant
Hybridization”.
Charles Darwin
Gregor Mendel
CONCEPTS OF GENOMIC BIOLOGY
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Mendel's Experiments Video
In 1865 Mendel delivered two long lectures that
were published in 1866 as "Experiments in Plant
Hybridization." This established what eventually
became formalized as the Mendelian Laws of
inheritance:
 The law of dominance. For each trait, one factor
(gene) is dominant and appears as the phenotype in
the first filial generation (F1). In the F2 generation the
dominant trait occurs more often, in a definite 3:1
ratio. The alternative form is recessive. In Mendel's
peas, tallness was dominant, shortness recessive.
Therefore, three times as many plants were tall as
were short. This constant ratio represents the random
combination of alleles during reproduction. Any
combination of alleles that includes the dominant
allele will express that form of the trait.
 The law of independent segregation. Inherited
characteristics (such as stem length in Mendel's pea
plants) exist in alternative forms (tallness,
shortness)—today known as alleles. For each
characteristic, an individual possesses two paired
alleles—one
inherited
from
each
parent.
Correspondingly, these pairs segregate (i.e. separate
or assort) in germ cells and recombine during
reproduction so that each parent transmits one allele
to each offspring.
 The law of independent assortment. Specific traits
operate independently of one another. A pea plant
might have a stem that is tall or short, but in either
case may produce white or gray seed coats.
However, the significance of Mendel’s work and his
insight into the mechanism of inheritance went
unrecognized until 1900 when three European
scientists, Hugo de Vries, Carl Correns, and Erich von
Tschermak reached similar conclusions in their own
research though they claimed to be unaware of
Mendel’s earlier theory of the 'discrete units' on
which genetic material resides.
The biological entity (factor) responsible for
defining traits was later termed a gene by Wilhelm
Johansen in 1910, but the biological basis for
inheritance remained unknown until DNA was
identified as the genetic material in the 1940s. Thus,
CONCEPTS OF GENOMIC BIOLOGY
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it was early in the 20 th century that the name “gene”
was given to the hereditary unity described by
Mendel decades earlier, and the study of genetics and
genomics began in earnest.
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2.2. GENES ARE CARRIED ON CHROMOSOMES.
At about the same time that genes were coming
into focus as having a role in inheritance, a series of
observations at the cellular level established:
 The existence of structures called chromosomes.
American graduate student, in 1902 at about the same
time that Mendel’s Laws of inheritance were being
rediscovered.
The developing theory stated:
 More than one gene is located on each
chromosome.
Thus, chromosomes are like a string of beads with
each gene represented as a bead. Along the length of
the chromosome (string of beads) there are genes for
many traits on each chromosome, and each gene
occupies a specific position on each chromosome
called a locus.
 The chromosomes are passed from one generation
to the next and carry genes to the next generation
as they are passed.
These points were incorportated into what we now
know as the Chromosomal Theory of Inheritance.
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 Chromosomes carry genes.
The notion that Mendel’s particulate hereditary
factors reside on visible structures called chromo-somes
was originally independently proposed by Theodor
Boveri, a German scientist, and Walter Sutton, an
CONCEPTS OF GENOMIC BIOLOGY
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2.3. THE CHROMOSOMAL THEORY OF INHERITANCE.
In the early years of the 20 th century Thomas Hunt
Morgan, who was skeptical about the theories of the
day concerning Mendel’s observations and the role of
chromosomes in inheritance, began conducting a
series of experiments using the fruit fly, Drosophilla
melanogaster, that ultimately convinced him of the
details of inheritance leading to what is called today
the chromosomal theory of inheritance. The general
tenets of this theory are given below:
 Multiple genes conditioning the cellular and
organismal traits an organism possesses are passed
from one cellular or organismal generation to the next
on chromosomes.
 Genes for specific traits reside at specific positions on
chromosomes called loci (singular locus).
 Most cells of an organism have homologous pairs of
chromosomes for each chromosome found in the cell.
 The complete set of chromosomes an organism
possesses is called it’s karyotype.
Figure 2.1. The complete set of 23 pairs of human
chromosomes is shown in the karyotype above. Note
that there are 22 pairs of autosomal Chromosomes, and
the X and Y sex chromosome “pair”. Thus, we say that
there are 22 pairs of homologous autosomal
chromosomes plus a pair of sex chromosomes (X or Y)
in humans, and humans have 46 (diploid number)
chromosomes in total.
The complete set of human chromosomes is shown
in Figure 2.1. Humans have 22 pairs of autosomal
chromosomes, and the X and Y sex chromosomes that
are present in males (XY) of females (XX). Thus, we say
that there are 22 pairs of homologous autosomal
chromosomes plus a pair of sex chromosomes (X or Y)
in humans. Humans have 46 chromosomes in total,
and the diploid number of chromosomes is 26.
CONCEPTS OF GENOMIC BIOLOGY
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Gametes, eukaryotic cells that pass chromosomes
to the next organismal generation, contain only a
haploid number of chromosomes (23 in the case of
homans). Thus, gametes have only 1 chromosome
from each pair found in a non-gametic cell.
Chromosome numbers are constant for a species, but
vary from one species to another.
 One of the chromosomes in each homologous pair
comes from the maternal parent while the other
chromosome in the pair comes from the paternal
parent.
 Although traits are conditioned by genes at specific
loci on the chromosomes, the gene at a given locus
coming from each parent may not be the same. They
can be either the dominant (according to Mendel’s law
of dominance) factor, ort he recessive factor. We now
call the nature of the factor (gene) at each locus, an
allele.
 When both the maternal and paternal homologous
chromosome contain the same allele, the organism is
said to be homozygous, but if the alleles contained at
the locus on the homologous chromosomes are
different the organism is said to be heterozygous.
 When an organism is homozygous, if the allele it bears
is the dominant allele, the organism demonstrates a
homozygous dominant genotype.
While a
homozygous organism bearing 2 identical recessive
alleles is considered homozygous recessive genotype.
 The genotype that an organism possesses in
combination with environmental factors is responsible
for production of the trait that we see. This is also a
definition of the phenotype of an individual, i.e. the
appearance of the individual resulting from the
interaction of genotype and environmental factors.
Thus, an organism can demonstrate a dominant
phenotype or a recessive phenotype.
What Mendel observed was the phenotype of his
pea plants. From observations of phenotype he
proposed a model for genotypic behavior of his
“factors” that we no know as genes. We also know
that these genes reside on chromosomes, and the
manner in which the chromosomes are passed to the
next generation provides the basis for Mendel’s law
of segregation that directly relates the behavior of the
chromosomes bearing the genes to the phenotypic
behavior that Mendel observed. However, there are
a number of instances where, although Mendel’s law
of segregation applies additional background is
required to appreciate how such Mendel’s work
applies.
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CONCEPTS OF GENOMIC BIOLOGY
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2.4. ADDI TIONAL COMPLEXITY OF MENDELIAN
INHERITANCE. (RETURN)
Once the simple laws of Mendel that governed
inheritance had been established and related to the
behavior of chromosomes, there were many
examples of situations that were not fully accounted
for with the simple laws. In the early 20 th century
there was great controversy, not just about the
chromosomal theory and its relationship to
inheritance of traits, but about other known examples
that appeared not to be explained by Mendel and the
chromosomal theory.
Resolution of these issues took decades and
required careful, thorough and well-designed
experiments too provide us with an understanding of
many of these situation. In fact a few of these
controversies were not fully resolved until the
genomic era and some are still being investigated
today.
Figure 2.2. Phenotypic description of the alleles of the C-locus for coat
color in rabbits. Note that this patterning is also found in many other
animals although the names of the phenotypes may differ.
2.4.1. Multiple alleles
(retrun)
Note that it is possible that for some traits more
than 2 alleles exist. In this case there is a hierarchy of
dominance among the multiple alleles. In any given
individual the more dominant allele of the 2 alleles it
posses is dominant, while the more recessive one will
be the recessive allele.
Examples of this phenomenon could be the ABO
blood type system and the rabbit coat color example
discussed shown in Figure 2.2. There are 4 unique
alleles that have been found at the C-locus, which is
one of 5 separate genetic loci that generate coat color
patterns in rabbits. The hierarchy of dominance that
has been observed at the C-locus suggests that the
wild type “large C” allele is the “most” dominant of
the alleles in the dominance hierarchy, and the “most
recessive” of the alleles is the “small c” locus. A
rabbit whose genotype is cc has an albino phenotype
while a rabbit with a CC genotype will be fully colored
(e.g. agouti, or black that is really dark grey as
described in the Figure 2.2). The second most
dominant allele is the chinchilla allele, c ch- allele, and
the ch-allele is intermediate in dominance between
the cch- allele and the c- allele.
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CONCEPTS OF GENOMIC BIOLOGY
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2.4.2. Incomplete dominance and co-dominance
A. Parents
(retrun)
It is also possible to have 2 alleles demonstrate an
intermediate phenotype in the heterozygous
condition.
This phenomenon is referred to as
incomplete dominance (similar to co-dominance),
and can be observed in Figure 2.2. where the
phenotype of a cchch or cchc heterozygous rabbit is
distinct and intermediate between the homozygous
(more) dominant cchcch and the homozygous (more)
recessive chch or cc phenotypes.
Another example is given in Figure 2.3., where
pure breeding (homozygous) red and white flowered
plants are crossed to give rise to intermediate
heterozygous pink plants.
In some plants the
intermediate heterozygotes appear as separate
distinct patches of color. This is typical of the
description of co-dominant traits where the distinct
alleles in a heterozygote are both visible. Thus, codominance and incomplete dominance may be a
distinction without a difference.
Rr
rr
RR
F1
Rr
Rr
Rr
rr
Rr
rr
Rr
Rr
B. Parents
Rr
rr
Rr
Rr
F1
Rr
Rr
RR
Rr
rr
Rr
Rr
rr
Rr
rr
rr
C. Parents
Rr
rr
Rr
F1
Rr
rr
rr
rr
Rr
Rr
Rr
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rr
Rr
Rr
rr
rr
rr
rr
Figure 2.3. Example of incomplete dominance in flower color of four
o’clocks. A) Red flowering x White flowering yields all pink flowers; B)
pink flowering x pink flowering yields 1 red : 2 pink : 1 while flowers;
and C) pink flowering x white flowering yields half pink and half white
flowers.
CONCEPTS OF GENOMIC BIOLOGY
2.4.3. Sex linked interitance
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(retrun)
Another example that differs from typical
Mendelian inheritance is sex-linked inheritance. In
organisms that have X and Y choromosomes, such as
Drosophila and humans, the female typically has a
pair of X chromosomes (XX) while the male has an X
and a Y chromosome (XY). So when a red-eyed
female fruit fly is crossed with a white-eyed male, the
result is all red-eyed progeny. This might seem like a
normal autosomal inheritance pattern where red eyes
are a dominant trait. However, in the reciprocal cross
(a white-eyed female crossed to a red- eye male. All
females will have red eyes, and all males will have
white eyes.
This demonstrates that the eye-color trait in
Drosophilla is a sex-linked trait, and it is conditioned
by a gene located on the X chromosome. Males
contribute an X-chromsomes only to their daughters,
as their sons must get the Y-chromosome. Females
contribute their X-chromsomes to both males and
females.
This phenomenon is pictorially demonstrated
using Punnet’s squares in Figure 2.4. below.
Figure 2.4. Demonstration of sex linked inheritance. The outcome as
demonstrated in the Punnet’s squares above is different based on
whether the male bears the dominant or recessive trait.
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CONCEPTS OF GENOMIC BIOLOGY
2.4.4. Epistasis
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(retrun)
Sometimes the phenotype of an organism does not
reflect the actual genotype. This can be the case
when one or more genes are epistatic to others.
Epistatic genes modify or eliminate the phenotype of
others so that the phenotype is not apparent. An
example of an epistatic gene might be a gene for
baldness. This gene would be epistatic to genes for
hair color, e.g. red hair or blond hair genes.
Another example of an epistatic gene is the c-allele
in rabbits given above. This allele produces a
phenotypically albino, white rabbit with pink eyes in
the homozygous recessive state. However, there are
at least 5 additional genetic loci that condition various
coat colors and patterns. Many of these other loci
have multiple alleles (as does the C-locus, see above),
but the rabbit will be albino if it is genotypically cc
(homozygous
recessive)
at
the
C-locus.
Demonstrating that the C-locus is epistatic to the
other coat color loci.
2.3.5. Epigenetics
(retrun)
More recently discovered phenomena involving
heritable changes in gene expression that are not
related to actual changes in DNA sequence, but rather
are related to chromosome structure and function
have also emerged. These phenomena are referred
to as epigenetic inheritance, and have emerging
importance in virtually all areas of biology and
medicine. We will discuss them in greater molecular
detail later, but they clearly had their beginning in
classical genetics.
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CONCEPTS OF GENOMIC BIOLOGY
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2.5. GENES ON THE SAME CHROMOMSOME ARE
LINKED.
In his studies with garden peas Mendel observed that
each of the 7 traits that he studied behaved
independently of each other. The mechanism that this
observation generated involved genes (hereditary
factors) assorting independently of each other. Thus,
when 2 factors (genes) were involved in a cross, each of
them behaved independently.
However, the chromosomal theory of inheritance
contradicts this observation by suggesting that genes
are linked together on chromosomes, and further
suggests that it is the chromosomes that are passed to
the next generation. If this is the case, how can genes
on the same chromosome assort indepen-dently?
Answering this question plagued the early development of genetics until the chromosomal theory of
inheritance emerged and the idea of gene linkage for
genes on the same chromosome were clearly shown by
Thomas Hunt Morgan and his colleagues about a
century ago.
Once established that it is chromosomes that assort
independently, it was clear that Mendel had fortuitously
chosen 7 genes on 7 different chromosomes to work
with, and as a consequence Mendel’s law of
independent assortment did not necessarily apply to all
genes since it was the chromosomes that assorted not
the genes per se.
The question has been raised as to whether Mendel
chose only data to work with that supported this
theory and disregarded other data or traits that did not
fit his theory to present. Whether this is true or not we
will never really know, but it surely doesn’t detract
from the important contribution Mendel’s work has
made to the science of genetics and genomic biology
by establishing an important set of rules that govern
the inheritance of traits.
2.5.1. Meiosis: chromosomes assort
independently (retrun)
The theory that allows us to explain the mapping of
genes begins with an understanding of the behavior of
chromosomes during meiosis. During the assorting of
diploid chromosomes sets like those found in somatic
cells into haploid chromosomes sets like those found in
gametes, it is possible to exchange parts of
chromosomes between different homologous sister
chromatids.
CONCEPTS OF GENOMIC BIOLOGY
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The process of meiosis begins with a diploid cell
containing 2 copies of the complete diploid genome
(diploid set of chromosomes) and ends with 4 cells
containing 1 copy of the haploid genome (haploid set of
chromosomes).
In the first meiotic division (meiosis I) homologous
chromosomes each consisting of 2 sister chromatids are
separated from each other to produce 2 haploid cells
with each chromosome consisting of 2 sister
chromatids. As these chromosomes (chromatids) align
at the mid-plane of the cell in late prophase I of meiosis,
the chromatids of homologous chromosomes may
overlap with each other and pieces of each
chromosome are sometimes exchanged. This process is
called crossing over or genetic recombination. Once this
exchange has taken place and meiosis I is completed,
the exchanged chromosomes become part of new
separate haploid chromosome sets in each of 2 haploid
cells.
Each of these cells undergoes a second meiotic
division where the sister chromatids are separated,
leading to 4 cells which have a unique combination of
traits that mixed the traits derived from each parent of
the original individual. Since this process is taking place
on each chromosome of the organism, the end result is
a likelihood that every gamete consists of a genome
that is unique compared to the parental genomes that
Figure 2.5. The stages of meiosis I and meiosis II are shown. This
involves two separate cell divisions that lead to the formation of 2
haploid cells from one diploid cell.
CONCEPTS OF GENOMIC BIOLOGY
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produced the individual. This mixing of genes at loci
along the length of chromosomes contributes much to
the genetic diversity required to make the process of
evolution work.
2.5.2. Mapping genes on chromosomes
(retrun)
Using Drosophila, Thomas Hunt Morgan and his
students accumulated a large collection of mutants
(allele pairs) for specific traits. As the collection of
mutants grew, it became clear that particular sets of
traits assorted together rather than independently as
Mendel had found with his peas. Morgan concluded
that genes for specific traits are linked together into 4
groups in Drosophila. This happened to equal the
number of chromosomes observed in Drosophila cells in
the microscope. By studying the process of meiosis as
described above, it was further established that pieces
of homologous chromosomes are exchanged when
chromosome numbers are reduced from 2 homologous
chromosomes per cell, to just a single chromosomal
homolog in the gametes that are fused to produce the
next generation.
From this initial idea of linkage of genes into groups
on chromosomes, Alfred Sturtevant, Morgan's student,
was the first scientist to make genetic or linkage maps
of fruit fly chromosomes. To do this Sturtevant
reasoned that since pieces of homologous
chromosomes can be exchanged during meiosis, the
frequency of this exchange provides a measure of the
relative distance between linked genes on the same
chromosome. Distantly located genes recombine more
frequently while nearby genes rarely recombine and are
closely linked. By measuring the frequency of crossing over between linked genes on the same chromosomes
the distance between genes can be estimated, and
genetic maps can be calculated and constructed.
From Morgan and Sturtevant’s work, the percentage
crossing-over became a chromosomal distance
measurement, and the definition of a unit of crossing
over, became know as the Centimorgan (=1% crossing
over between linked genes on the same chromosome).
Figure 2.6. Alfred Sturtevant’s first genetic map of
the Drosophila chromosomes.
CONCEPTS OF GENOMIC BIOLOGY
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2.6. QUANTITATIVE GENETICS: TRAITS THAT ARE
CONTINUOUSLY VARIABLE.
Mendel, perhaps fortuitously, chose to work with a
series of traits where he could find a pair of discrete
phenotypes. However, not all phenotypes are so clean
producing discrete classes. Above we have already
looked at examples of incomplete dominance, multiple
alleles, and epistasis, but for other traits phenotypes
are continuously variable between 2 extremes rather
than producing discrete phenotypic classes. Examples
of such traits are often related to height, weight, or
amounts of things. There are several books written on
the topic of quantitative inheritance, and one can linkout to online more brief treatments of the topic can be
found.
A number of additional references on
quantitative genetics can be found at the link-out, but
be aware that these may not be adequately edited,
and they are certainly incomplete, although they do
provide an overview of the area suitable for
understanding the relationship of quantitative genetics
to genomic biology. Also note that there are many
more complex issues involved in understanding
quantitative inheritance that require statistical
background beyond that expected here.
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In the human population there are not discrete
height classes. Height varies between over 7 feet tall
to under 4 feet tall in the human population; there
are not such things as pure breeding lines of tall
people and short people similar to what Mendel
developed in pea plants, and when two extremely tall
individuals are mated, the progeny, though perhaps
taller than average, are not all extremely tall like their
parents. Traits such as tallness are often referred to
as quantitative traits, and a separate branch of
genetics called quantitative genetics has emerged to
study and understand quantitative phenomena.
Figure 2.7. Description of a quantitative locus. A gene
contributes “d” average effect, but the value obtained lies
between +a and –a away from d.
CONCEPTS OF GENOMIC BIOLOGY
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In classical genetics, statistical approaches to
quantitative inheritance have emerged that provide
statistical tools for detailed analyses of quantitative
inheritance. These statistical approaches focus on
phenotypically defining 2 alleles at a putative
“quantitative locus”.
The midpoint between
homozygotes of the 2 alleles is defined as +d, and the
each opposing homozygotes would phenotypically
deviate from the midpoint by +a or –a (see Figure 2.7.).
In a heterozygote a phenotype closer to the
homozygous dominant (+a) than the midpoint (+d),
indicates a dominant character to that allele, and a
heterozygous phenotype closer to the homozygous
recessive (–a) results from a less dominant character to
the dominant allele. A measure of the heterozygote
distance from the midpoint then becomes a statistical
definition of incomplete dominance for such a
quantitative gene. Note that in Mendel’s tall versus
short pea plants the phenotype of the heterozygote is
almost precisely +d, indicating 100% dominance of the
tall allele over the short allele. In actual fact it is even
possible to have a super dominant allele that gives a
heterozygous phenotype more distant from the
midpoint than +a, a phenomenon that is sometimes
referred to as hybrid vigor.
In addition to statistical treatments of quantitative
inheritance it is also widely considered that
quantitative inheritance results from the interaction
of a number of different loci where each of these has
an effect on the final integrated outcome. This is
termed polygenic inheritance.
cM
Figure 2.8. Mapping quantitative trait loci using LOD scores.
This quantitative analysis identifies quantitative trait loci (QTLs)
located on various chromosomes and shows which regions of
the chromosome contribute significant genes to the quantitative
phenotype being investigated. The figure compares the severity
of an arthritic phenotype in hip and spine by location on the
chromosome.
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Polygenes are nonallelic genes at a set of loci
distributed in the genome that contribute to the
overall quantitative phenotype observed in the
organism. Figure 2.8 above shows how phenotypic
data and their proximity to known marker genes
allows the mapping of chromosome regions
influencing quantitative phenotypes referred to as
quantitative trait loci (QTLs). The distance measure
used in this map is the so-called LOD score that
relates phenotype to position on the chromosome.
The LOD score method of locating regions of
chromosomes that influence quantitative inheritance
relies on having numerous closely related genetic
markers on chromosomes.
Although the method has been available for some
time, the advent of genomic techniques for
identifying and mapping DNA sequence markers on
chromosomes has markedly improved the accuracy
and facility of identifying QTLs in genomes.
Additionally, the availability of complete genome
sequences makes it possible to not only identify
regions of the chromosome related to phenotypes,
but to actually identify the specific causally-related
genes. The QTL approach has found wide application
ranging from the mapping of human disease QTLs
(example in Figure 2.8), to applications in plant and
animal breeding, and to application in evolutionary
and population genetics among others.
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2.7. POPULATION GENETICS.
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Statistical genetic theories have also become a
major consideration in the discipline of population
genetics. In the context of a population, the
frequency of individuals having a given genotype is
related to the frequency of each allele in the breeding
population. If you assume that mating in a population
is random and very large to assure that it is
homogeneous, then the frequency of genotypes in
the subsequent generation will be directly related to
the frequency of alleles in the gamete pool that
produces that generation. Thus, where there are only
TABLE 2.1.
Female gametes
Gamete /
Frequency
Male
game
tes
CONCEPTS OF GENOMIC BIOLOGY
R/ p
r/q
R/p
r/q
RR / p2
Rr / pq
Rr / pq
rr / q 2
2 alleles for a given locus found in the population, and
p = frequency of dominant allele gametes while q =
frequency of the recessive allele gametes, p + q = 1.
As is shown in table 2.1., the
CONCEPTS OF GENOMIC BIOLOGY
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frequency of homozygous dominant individuals in the
population should be p2 and the frequency of
homozygous recessive individuals will be q2.
Heterozygotes should then be found at a frequency of
2pq, and in total p2 + 2pq + q2 = 1. This is the binomial
expansion of (p + q)2.
If this looks familiar, recall the Punnett’s squares
that we did showing gene segregation in the F-2
generation. In that case since heterozygotes produce
gametes, half of which carry the dominant allele and
half of which carry the recessive allele, i.e. p = q = 0.5.
Substituting these gamete allele frequencies into the
binomial equation above, we get the 1:2:1
segregation ratios we expect.
However, in a population, where there are both
homozygotes and heterozygotes all producing
gametes, p will not usually equal q, and a different
equilibrium of gametes and genotypes will be
established and maintained through time. This
description is called a Hardy-Weinberg equilibrium.
In order for a population to sustain a Hardy Weinberg
equilibrium
additional
factors
(assumptions) must be in place or the equilibrium will
not be maintained. In addition to a large population
and random mating within the population as
discussed above, it is also necessary that there be no
mutation
occurring in the population and that there be no
natural selection taking place for the alleles or linked
genes in question. Additionally, there should be no
gene flow (migration into or from the population)
taking place, and the population should not have
gone through a dramatic change in size recently that
may have related to genetic drift in the population. It
should also be noted that the equations given above
relate only to diploid species. Some species found in
nature are natural polyploids (having more than 2
sets of chromosomes), and the equations for
describing the behavior of polyploids are different
from the bionomial expansions described above. Also
other changes in the equations are required for
situations where there are more than 2 alleles found
in a population.
As was with quantitative genetics, the introduction
of tools from genomic studies into population
genetics have greatly facilitated the investigation of
genes in populations, and this is particularly relevant
in the investigation of the human population.
Population genetic studies using molecular markers
for important health-related genes are now common
place in Public Health studies.
(RETURN)