GENETICS
after Mendel
/A/ GENE as a material substance
in chromosome
/B/ „SWITCH OFF/ON“ of gene
and basic idea of EPIGENETIC
/C/ Non-mendelian variability
/D/ GENETIC ILLNESS PROBABILITY for
X-linkded and Y-linked genes
Problematic or 100% correct
Mendelian genetics?
Menel theory of organism heredity was very precise and based on postulating of
2 alleles (one from father = paternal; one from mother = maternal ) and very precise
mathematical rule of combination of these alleles (in crating of gamets, or in crating of zygota
from haploid gamets). Mendel was genial man, becaouse this postulate was derived from
statistic of phenotype, he was not able to se microscopical structure of gene in chromosome or
proteins which modifiy gene expresion. These postulate and 3 Mendel Laws are true and
valid for computing of heredity ( transfer probality from parents for many anatomy
marker, pigment of hair ,shape of nose, enzyme aktivity, anemic blood cell, and many
other….)
However another medicial experts during 20th century have found in patients and experimental
animal set the exceptions to the Mendel rule. Mendel’s laws are correct, however in real
life none of the three laws is completely correct for all genes and all genetic
transfr of illnesses. We know now that some hereditary factors are codominant, not
completely dominant, to others; one can cross red with white petunias and get pink offspring, not
red or white offspring as Mendel would have predicted. We also know that the law of segregation
is not always true in its literal sense. In humans, the X and the Y chromosome are not passed
along entirely at random from a father—slightly more boys than girls are conceived. And we also
know that not all hereditary factors assort independently. Those that are located close together
on the same chromosome tend to be inherited as a unit, not as independent entities. This aspcet
will be presented in next chaptr /A/ and /B/ and /C/, and remeber that all these principes can be
combined in ral organism and real patient.
/A/ GENE as a material
substance in chromosome
• MENDEL:
Endowment / Natural Ability
• 20th CENTURY:
Gene / Genetic information
Short history of material
substance exploring :
1871
1953
Structure of DNA and components
(learn the names of acids and possible combination of acid paris
in RNA and DNA)
Example of Genetic code
(C = cytosine, G = guanine, A = adenine,
T = thymine…) of 1% of 3rd human
chromosome
Example of one gene
Every human organism have “2 genetic
message“ of one gene
EUKARYOTA(EUKARYOTA) Human cells: „Display“ of
gene into real protein molecule
Different „delivery of information“
PROKARYOTA
/B/ „SWITCH OFF/ON“ of gene
and basic idea of
EPIGENETIC
Two important facts:
1/ Human bodies have such different parts, like
skin, eyes, and heart, even if almost all our
cells have the same DNA?????? It is because
different parts of our DNA are switched “on” and
“off” in different cells!
2/ Two rabbits (2 same genetic twins) have the
same set of DNA code in muscle. However one
rabbit can be famous sprinter and second not,
becouse is in the farm where is a lot of smoke.
Then, let us take a close look at how the DNA is
organized within the cells and translated:
Nice analogy
A person’s genotype is their unique sequence of DNA. More
specifically, this term is used to refer to the two alleles a person has
inherited for a particular gene.
Phenotype is the detectable expression of this genotype
Nice analogy
(with described possible feedback)
What is the microcopical mechanism
of this OFF/ON switching ??
Well-packed DNA, wrapped tightly around histones, is
not accessible to the cellular machinery that reads the
information on the DNA and turns it into proteins.
(Analogy: Imagine a book with some pages held together by a paper clip. You cannot read
what is on those pages! They must be accessible to you before you can read them. The
packaging of the DNA has the same effect.
The human genome has more than 20,400 genes which contain
information for the formation of proteins. This sounds like a lot, but
proteins are extremely important for the proper functioning and
development of our bodies, so we need all these proteins. But we do
not need all of them at the same time, and it would be difficult for a cell
to deal with producing and managing so many types of protein
simultaneously. Thus, only a few proteins are produced at the same
time in a cell. This means that only a few genes are active (switched
“on”) at a time in any cell. The genes that are “on” will determine what
that cell can do—the function of the cell. Some genes need to be active
in more than one body part or cell type, while other genes are active
only in specific cells. Some genes are active only in specific time (new
born time, beast-feeding, etc)
Structure of DNA code
(INTRONs and EXONs)
„delivery of information“
MUSCLE CELL
SMOOTH MUSCLE CELL
FIBROBLAST
BRAIN NEURON
• Epigenetic changes alter gene activity
without modifying the DNA
sequence and are essential to normal
development.
Epigenetic regulation is based on molecular mechanism of
:
• A gene is switched “on”
when the portion of
chromatin where it is
located “opens.” This
process involves proteins
that add little chemical
modifications to histones or
to the DNA. The
modifications cause the
histone to slide on the DNA
or cause the DNA to
unwrap from the histone,
allowing the chromatin to
open and the information on
the gene to be read.
• Epigenetic modifications caused by these factors can be “memorized”
for long periods of time. When a cell divides, its epigenetic modifications are
passed on to the next generation of cells. It is interesting that this situation is different in
reproductive cells. Most epigenetic modifications are erased during reproduction. In animals, the
modifications that persist only last for about one or two generations.
• The epigenome of an organism is fluid, which means that it is constantly changing. It is shaped in
response to stress, in ways that last from hours to months, years, or an entire life. For example,
the epigenome of mice exposed to very stressful situations can change.
Example: Epigenetic events that alter chromatin
structure to regulate programs of gene expression have been
associated with depression-related behavior, antidepressant
action, and resistance to depression or ‘resilience’ rat.
You can see to very
nice review article:
Epigenetic for many illnesses is importnat and investigator bring
new view to many mechanism their development,
epigenetic iaspect are computed to modern
pharamcology studies
Positive example of epigenetic
Rat-Mom’s licking appears to provoke epigenetic changes in genes that can
help pups manage stress. The most important stress hormone for mammals
is called cortisol, and the level of cortisol in our bodies is regulated by
glucocorticoid receptors. The gene for the glucocorticoid receptor is highly
influenced by maternal care. Highly licked rat pups have lots of
glucocorticoid receptors, so they can manage their body’s stress response
rapidly and get back to normal quickly.
References
Danese, A., Moffitt, T.E., et al. (2009) “Adverse
childhood experiences and adult risk factors for
age-related disease: depression, inflammation,
and clustering of metabolic risk markers.” Arch
Pediatr Adolesc Med. 163 12: 1135–43.
Lucassen, P.J., Oomen, C.A., et al. (2015)
“Regulation of adult neurogenesis and plasticity
by (early) stress, glucocorticoids, and
inflammation.” Cold Spring Harb Perspect Biol. 7
9: a021303.
Lucassen, P.J., Naninck, E.F., et al. (2013)
“Perinatal programming of adult hippocampal
structure and function; emerging roles of stress,
nutrition and epigenetics.” Trends Neurosci. 36
11: 621–31
Negative exampel of epigenetic
Example of epigenetic changes
monitoring
https://www.embopress.org/doi/full/10.15252/msb.20156520
• https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.118.312497
• Epigenetic stimul can hit the organism in
prenatal and also in postnatal time
• Some epigentic result can be detected in
F1 and also in F2 generation or later
Nice review for advanced reading:
https://labs.la.utexas.edu/champagne/files/2018/01/Chpt24TransEpi.pdf
/C/ Non-mendelian
variability
CROSSING OVER
Certain final gamets have combination of
gene from
paternal and maternal chromosome
(this is not described by Mendel laws)
BASIC SUMMARY
of „post“-mendelian genetic is
defined by MORGAN RULEs:
1) Genes are always stored in a linear sequence on the chromosome.
2) The genes of one chromosome form a linkage group. The number of
linkage groups of an organism (for example human) is the same as the
number of pairs of homologous chromosomes of the respective
organism.
3) Gene exchange can take place between the genes of a homologous
pair of chromosomes through crossing-over. The frequency of crossingover
is proportional to the distance of the genes.
/C/ GENETIC ILLNESS PROBABILITY
for X-linkded and Y-linked genes
Homework:
draw chromosome and compute%