Biology
8. Basics of genetics
Doc. RNDr. Jan Hošek, Ph.D.
hosek@mail.muni.cz
Department of Molecular Pharmacy
FaF MU
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History of genetics 10 000
BC.
• neolithic revolution - the emergence of agriculture
• selection of the most suitable individuals for further
breeding/cultivation
460-
370 BC.
• Hippokrates
• „If a phlegmatic person is born a phlegmatic person, a
choleric person is born a choleric person, an epileptic person
is certainly born from epileptic parents…“
1820
• C.F. Nasse
• described the inheritance of hemophilia - sex-linked
1822-
1884
• Johann Gregor Mendel
• The foundations of genetics are laid
1900
• de Vries, Tschermak a Correns
• the rediscovery of Mendel's laws
1906
• William Bateson
• used the term genetics, heterozygote and homozygote, F1
and F2 etc.
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History of genetics
o Wilhelm Johannsen - introduces the terms gene, genotype and
phenotype
o Thomas Hunt Morgan - work on chromosomes (Chromosomes and
heredity)
• the model organism used friut fly (Drosophila melanogaster)
• new knowledge about genes and gene linkage
• In 1933 he became the first geneticist to win the Nobel Prize
• genes are always stored in a linear sequence on the chromosome
• the genes of one chromosome form a linkage group
• gene exchange can take place between the genes of a homologous pair of
chromosomes through crossing-over. The frequency of crossing-over is
proportional to the distance of the genes
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Genetics
o is a science dealing with the heredity and variability of living systems (and their
causes)
o monitors the variability, differences and transmission of genetic and hereditary
traits between parents and offspring and also between offsprings themselves
GENETICS
the science of heredity
DNA replication segregation, combination,
recombination
similarity diversity
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What is a "gene" in functional terms?
• Genes (factors, traits) = constant
factors controlling phenotypic traits
1866
J. G.
Mendel
• "One mutant gene = one metabolic
block"
cca 1900
A. Garrod
• "One gene = one enzyme"
30‘s of the 20th century
G. Beadle a E. Tatum
• "One gene = one polypeptide"
Second
half of 20th
century
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A bit of terminology
o genotype – a set of specific
genes (alleles) of an organism
o phenotype - manifestation of
characters
Genes traits
genotype phenotype
environmental
influence
o gene – a section of DNA that
codes for one functional
transcript (mRNA, rRNA,
tRNA, siRNA, lncRNA,...)
o allele – a specific form of a
gene
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„Classic“ (mendelian) heredity
o Heredity of qualitative traits
Inter-allelic relationships I.
o complete dominance - the dominant allele
completely suppresses the expression of the
recessive allele
• a dominant allele is therefore one that manifests itself
even in a heterozygous combination
o incomplete dominance - the dominant allele
does not suppress the recessive allele completely,
the recessive allele is also partially expressed
Dominant
homozygous
Recesive
homozygous
Heterozygous
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Inter-allelic
relationships I.
https://user.mendelu.cz/urban/vsg1/mendel/klas_interakce1.html
complete dominance incomplete dominance
Genotype Phenotype Genotype Phenotype
phenotypic
manifestation
complete dominance incomplete dominance w/o dominance
incomplete dominance
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Inter-allelic relationships II.
o Codominance - both present alleles are fully
expressed in the heterozygote and do not affect
each other
o Superdominance - a heterozygote (Aa) shows
a stronger form of the trait than both types of
homozygotes (aa, AA)
• Heterosis effect - mainly used in agriculture (e.g. F1
tomato hybrids)
• The heterozygous effect is caused by the accumulation of dominant
heterozygous genes from both parents in the offspring (F1). For example, one
parent has AABBccdd, the other parent has aabbCCDD, an offspring with a
heterozygous effect has AaBbCcDd. Dominance theory assumes that
dominant alleles are better than recessive ones. Those who have more genes
with dominant alleles have better results.
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Mendel's laws of heredity
o First experiments on pea (Pisum sativum) = suitable experimental model
o worked with pure parental lines (homozygotes)
o monohybridisms
o applications of mathematics and statistics
https://ib.bioninja.com.au/standard-level/topic-
3-genetics/34-inheritance/mendels-laws.html
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Mendel‘s experiments
https://www.sciencelearn.org.nz/images/2478-pea-traits-studied-by-mendel
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1st law on the uniformity of F1 hybrids
o If we cross two homozygotes, their offspring of the F1 generation
are all the same in the observed trait. Reciprocal crosses with any
individuals of the F1 generation give identical results.
2nd law of splitting in the offspring of hybrids
o When heterozygotes are crossed, the genotypes and phenotypes
of the resulting individuals can be expressed as a ratio of small
whole numbers. A genotypic and phenotypic split ratio is created.
The offspring will show a recessive trait.
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Punnett square
gametes
gametes
B – dominant allele for
yellow color
b – recesive allele for
green color
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3rd law of independence of alleles
o A genotype is a set of individual genes that determine traits. Each
trait is determined by a pair of separate alleles
4th law of segregation of alleles
o Pairs of separate alleles diverge during maturation, and one of the
two alleles passes into each gamete
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5th law of independent choice
o includes more characters → alleles do
not influence each other, so a spectrum of
different combinations is created
Generalization for n- hybridism
n = 1 n = 2 generally
number of gamete types of the
hybrid
2 = 21 4 = 22 2n
number of zygote types 3 = 31 9 = 32 3n
number of different
homozygouts in both allele pairs
2 = 21 4 = 22 2n
number of breeding novelties 0 = 21-2 2 = 22-2 2n-2
genotype ratio in F2 (1:2:1)1 (1:2:1)2 (1:2:1)n
phenotype ratio in F2 under full
dominance in all allele pairs
(3:1)1 (3:1)2 (3:1)n
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Deviations from Mendelian cleavage ratios
o a situation where Mendel's laws do not fully apply
o deviations from Mendelian rules (referred to the genetics of the human
individual):
o Reduced vitality (lethality) of gametes and zygotes
o Gene linkage
o Gene interaction
o Linked to gender
o Extranuclear inheritance
o Polygenic inheritance
o Variable expression
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Reduced vitality (lethality) of gametes and zygotes
vital > subvital > semilethal > lethal
recessive lethality AA Aa aa
recessive lethality of the dominant allele AA Aa aa
dominant lethality AA Aa aa
gametes - haplontic selection zygotes - diplontic selection
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Recessive lethality of the dominant allele
o Manx cat
o MM – lethal
o Mm – without tail
o mm – normal
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Gene linkage
o when two genes are linked, free combinability does not apply = deviations from
the phenotypic split ratio of 9:3:3:1 in F2 and 1:1:1:1 in B1 generation
o genes on one chromosome are linked to each other
o trans phase - dihybrid AaBb, which has genes A and B located on different pairs of
chromosomes, forms gametes of genotypes AB - Ab - aB - ab in a ratio of 1 : 1 : 1 : 1
o cis phase - dihybrid AaBb, which has genes A and B located in one pair of
chromosomes, forms gametes of type AB – Ab – aB – ab in different proportions
o the reason is crossing-over between non-sister chromatids
• gametes with non-recombined (AB, ab) and recombined (Ab, aB) genotypes are produced
• the probability of crossing-over decreases with the distance between the two monitored genes
o the linkage strength (= distance between genes) is determined by Morgan's
number, which expresses the proportion of recombinants and is given in
centimorgans (1 cM = 1% recombinant), the recombination process occurs with a
relatively low probability
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Linkage phase cis/trans
Linkage phase cis Linkage phase trans
parental gametes parental gametesrecombinant
gametes
recombinant
gametes
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Two possibilities of exchanges between nonsister
chromatids
Chromosome pair gametes
https://user.mendelu.cz/urban/vsg1/mendel/klas_vazba1.html
Possible crossing-overs
between genes
more less
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Possibilities of chromatid recombination
Incorporation of BrDU
during S-phase
24
Gene interaction
o Reciprocal interaction
• interaction without a change in the cleavage ratio, the observed trait occurs
in multiple forms, each of which is determined by one of the combinations of
parental gene alleles
o Epistasis
o Inhibition
o Complementarity
25
P
F1
F2
FFOO ffoo
FfOo
FFOO
ffoo
FfOo
FfOo
FfOo
FfOo
FFOo
FFOo
FfOO
FFoo Ffoo
Ffoo
FfOO ffOO ffOo
ffOo
9 : 3 : 3 : 1
F-O- : F-oo : ffO- : ffoo
Reciprocal interaction
(a)
Wyandotts
R- pp
(b)
Brahmans
rr P-
Hybrid
(a) x (b)
R- P-
Leghorns
rr pp
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Gene interaction
o Reciprocal interaction
o Epistasis
• gene encoding the corresponding trait has no chance to express itself,
because its superior gene does not allow it
• The cleavage ratio is changed
o Inhibition
o Complementarity
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Dominant epistasis
o In dominant epistasis, it is sufficient for at least one dominant allele to be
present in the epistatic trait pair to suppress the effect of the subordinate
allelic pair. Dominant homozygotes and heterozygotes in an epistatic
pair therefore have the same phenotype regardless of what traits they
carry in the hypostatic pair.
epistatic gene (allele) Y
hypostatic gene I, i
Y…intense yellow flavone
I… creamy yellow flavone
Dahlia
variabilis
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Recessive epistasis
o In recessive epistasis, the dampening effect of an epistatic trait pair is
only manifested if an individual is recessive homozygous for that trait.
Salvia viridis
var. horminum
P… pink antocyan
A… pink → purple
pp > A-
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Inhibition
o Inhibition is similar to dominant epistasis in many ways. However, the superior trait
pair has no own phenotypic expression, its dominant allele only blocks the effect of
other traits. They can therefore only manifest if the inhibitory allelic pair is in a
recessive homozygous state.
C … red coloring
I … color inhibitor
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Complementarity
o If the interaction of dominant alleles from two or more trait pairs is
needed for a certain phenotypic manifestation, this is called
complementarity, or double or duplicate recessive epistasis.
Lathyrus odoratus
C… dye precursor
R… enzyme
32
o The gene is found on
the gonosomes →
phenotypic
manifestation depending
on sex
https://en.wikipedia.org/wiki/X-
linked_dominant_inheritance
Linkage to gender
33
Further deviations from Mendelian cleavage
ratios
o Extranuclear inheritance - mitochondrial DNA from mother only
• in plants, chloroplast DNA from the female plant only
o Polygenic inheritance – the trait is coded by several genes → the
rules for n-hybrids and crossing-over apply here at the same time
o the trait has incomplete penetrance - it may not manifest itself in
100% of individuals, but in some people it does not manifest, or the trait
is obscured and difficult to observe
o the trait has a variable expression - in people with the same genotype,
we observe different intensity of manifestations of the same trait
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Inheritance of quantitative traits
o The manifestation
of the trait takes on
different values ​​→
continuous
variability
Qualitative trait vs. quantitative trait
low high small big
diameter
Mendel's
experiment
with plant
height
Galton's
experiment
with seed
diameter
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Inheritance of quantitative traits
o for research on the polygenic and multifactorial inheritance of human
hereditary traits, the follow-up of twins is particularly useful
• dizygotic twins, growing up in the same environment, give us a picture of how the
same external factors act on two individuals with different (albeit slightly) genotypes
• monozygotic twins provide us with a unique opportunity to evaluate two individuals
with the same genotype
• if these monozygotic twins also grow up each in a different environment, we can
evaluate the effect of different environments on individuals with the same genotype
o we evaluate:
• concordance for a certain trait (match - both individuals have the observed trait)
• discordance for a certain character (disagreement - one of the twins does not have the
given character)
• heritability is a value indicating to what extent the value of traits depends on the
genotype of an individual and how much the final value of a trait is the result of external
factors
Trait heritability HB (%)
mouse tail lenght 60
litter size 15
friut fly number of abdominal hairs 52
wing length 45
human asthma 80
diabetes 70
Heritability estimates for various traits (%)
Concordance of some characters
in monozygotic (MZ) and dizygotic (DZ) twins
trait Conkordance (%)
MZ DZ
Blood groups 100 66
Eye color 99 28
Mental retardation 97 37
Measles 95 87
Idiopathic epilepsy 72 15
Schizophrenia 69 10
Blood pressure 63 36
Diabetes 65 18
Identical allergy 59 5
Tuberculosis 57 23
Cleft lip 42 5
Crooked legs 32 3
Breast cancer 6 3
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Epigenetics
o Epigenesis - explains the principle of individual development: the resulting
organism is not preformed, but arises creatively on the basis of inherited
information and internal and external influences.
o Epigenetics - studies heritable changes in gene expression that occur
without changing DNA sequences.
o Genomic imprinting - a reversible process where sex-specific modification
of genes in the parental generation leads to functional differences between
the paternal and maternal genomes (alleles) in the offspring
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Mechanisms of imprinting
o DNA metylation
o Acetylation of
histones
41 Schagdarsurengin, U., Steger, K. Epigenetics in male reproduction: effect of paternal diet on sperm quality and offspring
health. Nat Rev Urol 13, 584–595 (2016). https://doi.org/10.1038/nrurol.2016.157
affected normal normal
( carrier )
children :
parents :
mutant father healthy parents mutantn mather
Maternal imprinting of the mutated locus results
in a different phenotype of the offspring
Incorrect imprint of P-allele (insuline growth factor) or M-allele
(growth-suppressing H19-RNA) leads to Beckwith-Wiedemann‘s
syndrome
P
M
P
M
normál
BWS
Igf2 H19
(J. B. Beckwith & H. R. Wiedemann 1964)
44
Front. Genet., 27 August 2018
Sec. Epigenomics and Epigenetics
Volume 9 - 2018 | https://doi.org/10.3389/fgene.2018.00342
45
Front. Genet., 27 August 2018
Sec. Epigenomics and Epigenetics
Volume 9 - 2018
| https://doi.org/10.3389/fgene.2018.00342