Human Genetics

Nor Isnida Ismail

 Course Learning Outcome (CLO)
Examine the fundamental concept and technical knowledge of animal cell culture in written assessment (C4, PL01)

Prepare written communication related to cell culture techniques (A2, PLO5)

Perform animal cell culture using the basic principles of aseptic techniques (P3, PLO2)
 Synopsis
• This course aims to introduce the important
concepts of genetics and fundamental
principle in genetics.
• This course provide understanding of human
chromosome, Mendelian inheritance and
disease, effect of genes of the phenotypes
which determine the human trait, genetic
susceptibility and genetic of cancer
 Course learning outcomes
• Upon completion of this course students
should be able to:

1)Apply the knowledge, concept and fundamental principles of the science of

genetics in human biology, human inheritance disease and disease
association with the changes in gene to phenotype.
2) Relare the knowledge about genetic basis of hereditary, chromosomes
structures and functions on human abnormalities.
3) Collaborate and adhere with team members in group work (A3).
Mendelian Inheritance

Human Genetics
Nor Isnida Ismail
• What genetic principles account for the passing of
traits from parents to offspring?
• The blending hypothesis
• Genetic material from the two parents blend
together
Fig. 14-1

BE @

I i
'

÷
Fig. 14-2a

TECHNIQUE

€
Experiment with garden peas
True breading (produce
1 offspring of the same variety
when they self-pollinate)

Parental
generation
(P) Stamens
Carpel
3

4
Monohybrid
homozygous Rr heterozygous
Crosses RR /
-

-
rr

By

¥ physical
88
00
0 0
 Dihybrid Crosses

8
 Mendel discovery/ concept
“heritable factor” > gene
alternative versions of genes : variations
1st
in inherited characters > allele

each character an organism inherits two

alleles, one from each parent & assort 2nd
independently

Alleles of a gene are either dominant or

recessive
3rd

¥
law of segregation: 2 alleles for heritable
character separates/ segregates during
4th
gamete formation & end up in different
gametes
Fig. 14-4

Lochs =
colour

Adele
purple/ white /
'
: .
"

Allele for purple flowers

Homologous
Locus for flower-color gene pair of
chromosomes

Allele for white flowers

 Mendel’s Principles
• The Principle of Dominance: In a ÷:
be seen /

heterozygote, one allele may conceal the

presence of another. Pioneer

• The Principle of Segregation: In a

heterozygote, 0
two different alleles segregate
-

from each other during the formation of

gametes.
Applications of Mendel’s Principles
• Mendel’s principles can be used to predict the
no
-

outcomes of crosses between different strains

_

of organisms.
• Three methods to predict outcomes
– The Punnett Square Method
– The Forked-Line Method
– The Probability Method
The Punnett Square Method
Dd Ggww ✗ DdGgWw
The Forked-Line Method
Dd ✗ Dd G- 9×0-9 for an Intercross
Wwxww

DD AG
C-
Dd 9

Dd Eg
dd 59

0
 ⇒
Probability
• The probability of an event is the frequency of that event in
-
the sample space.

£-8
• For a coin toss:
– The probability of heads is 1/2.
– The probability of tails is 1/2.
• For two heterozygotes (Gg) producing an offspring:
- a.gas
– The probability of GG is 1/4.
– The probability of Gg is 1/2.
– The probability of gg is 1/4.
Fig. 14-UN1

Pp ✗
Pp
J
PpYyRr X ☐
Ppyyrr
pppppppp

-
 Probability
• The sample space is the
collection of all events.

c-
• What is the probability
two events, A and B, will
occur together?
• What is the probability
that at least one of the
two events, A or B, will
occur at all?
 The Multiplicative Rule

5=-0
• If the events A and B are independent, the
probability that they will occur together, denoted
P(A and B), is P(A)  P(B).

• Example: probability of drawing the ace of hearts,

P(A and H)
P(A) = 4/52 P(H) = 1/4
P(A)  P(H) = 4/52  1/4 = 1/52
 The Additive Rule

→
• If the events A and B are independent, the
probability that at least one of them occurs,
denoted P(A or B), is given by☐P(A) + P(B) − [P(A) 
P(B)].
PLA ) 1- PBC ) -

[ pc A) xp (B)]
• Example: Probability of a drawing an ace OR a heart,
P(A or H)
P(A) = 4/52 P(H) = 1/4
P(A or H) = (4/52) + (1/4) − (4/52  1/4) = 16/52
 The Additive Rule

53
• If the two events do not overlap in the sample space,
-

they are said to be mutually exclusive.

• In this case, P(A)  P(B) = 0, and the Additive Rule
reduces to
P(A or B) =P(A) + P(B)
• Example: probability of drawing an ace or a king, P(A
or K)
P(A) = 4/52 P(K) = 4/52
P(A or K) = 4/52 + 4/52 = 8/52
←
c- ]
 Mendelian Principles in Human
Genetics

8⇔
• Obstacles to Human Genetic Analysis
– Incomplete family records
– Small number of progeny
– Uncontrolled environment

• Despite these obstacles, many human genetic

traits have been described.
Pedigree Conventions

E-
• Pedigrees are
diagrams that show
the relationships
among the members
of a family.
Inheritance of a Dominant Trait
• Every individual who carries the

EÉ
dominant allele manifests the
trait.

• Every affected individual is

expected to have at least one
affected parent.

• If a dominant trait is associated

with reduced viability or
fertility, most people who show
the trait are heterozygous, and
half their children should
inherit the condition.
Inheritance of a Recessive Trait
• Recessive traits may occur
in individuals whose
parents are not affected.

• Rare recessive traits are

most likely to appear in a
pedigree when spouses
are related to each other.
Mendelian Segregation in Human
Families
 Genetic Counseling:
Nonpolypoid Colorectal Cancer
Genetic Counseling: Albinism
"
"
"
°
°
^^ *

✓
 Key Points
• Pedigrees are used to identify dominant and
-
=
recessive traits in human families.

• The analysis of pedigrees allows genetic

counselors to assess the risk that an individual
⇔
-

will inherit a particular trait.

-
 Extending Mendelian Genetics for a
Single Gene
• Inheritance of characters by a single gene may
deviate from simple Mendelian patterns in the
following situations:
– When alleles are not completely dominant or

⇒
recessive
– When a gene has more than two alleles
– When a gene produces multiple phenotypes
 Mendel’s Work
• Each trait that Mendel studied was controlled
by a single gene with two alleles.
• Genes may have more than 2 alleles.
• Different alleles may affect the phenotype in
different ways.
 Allelic Variation
and Gene Function
The diverse kinds of alleles of genes
affect phenotypes in different ways.
""" "" "" " "

"
"
" " "°
expressed 17 is not completely expressed in fi generation
Incomplete Dominance
• The phenotype of the
heterozygote is
O
midway between the
-

phenotypes of the

⇒
two homozygotes.
• One allele is partially,
or incompletely,
0 dominant over the
other.
cuh
Codominance : : : :*
alleles are acting
.

• The heterozygote
expresses the
phenotypes ofC) both
(
homozygotes.s
• Neither allele is
dominant.
For any character, dominance/recessiveness
relationships of alleles depend on the level at
which we examine the phenotype

¥
• Tay-Sachs disease is fatal; a dysfunctional enzyme
causes an accumulation of lipids in the brain
– At the organismal level, the allele is recessive
– At the biochemical level, the phenotype (i.e., the
=
-

enzyme activity level) is incompletely dominant ma

– At the molecular
-
-
level, the alleles are codominant
 Multiple Alleles of a Single Gene'
⇐
Most genes exist in populations in more than two allelic
forms

• The most common

alleles in nature in the
wild-type allele.

=
• All other alleles are
mutants.
Fig. 14-11
Allele Carbohydrate
IA A
IB B
i none
(a) The three alleles for the ABO blood groups
and their associated carbohydrates
-

Red blood cell Phenotype

Genotype appearance (blood group)

IAIA or IA i A

IBIB or IB i B

IAIB AB

ii O
(b) Blood group genotypes and phenotypes
Allelic Series
• An allelic series describes

÷
the dominance hierarchy
of multiple alleles.

• A null allele is
nonfunctional.
• A hypomorphic allele has
partial function..
 Testing Mutations for Allelism
alle / dominant dominant -
BB
ey
-

Homozygous ≤
recessive Bb
recessive
=

Heterozygous - = bb

C )
[ 3
* Variation Among the
=
Effects of Mutations
• Visible mutations

By
• Sterile mutations
• Lethal mutations
Genes Function to Produce
Polypeptides
Dominant and Recessive Mutations

o
☐ o
=
-
-

o
-

=
 Key Points
Genes often have-
• O multiple alleles.
① @ ③
• J
Mutant alleles may be dominant, recessive, incompletely
dominant, or codominant.④

umping Hit
• If a hybrid that 0
-
inherited a recessive mutation from each of its
parents has a mutant phenotype, then the recessive
=
mutations are alleles of the same gene; if the hybrid has a
wild phenotype, then the recessive mutations are alleles of
_

different genes.
 Key Points
• Most genes encode polypeptides.
DD / 99 ""

• In homozygous condition, recessive mutations often abolish

or diminish polypeptide activity.

• Some dominant mutations produce a - polypeptide that

interferes with the activity of the polypeptide produced by
the wild-type allele of a gene.
 Gene Action:
From Genotype to Phenotype
Phenotypes depend on both
environmental)andC-
C genetic factors.)
 Influence of the Environment
• Genes function in a (biologicalI and physical_

environment.

==
• Examples
– Drosophila shibire mutation (temperature)
-

– Phenylketonuria (diet)
– Pattern baldness (gender)

multifactorial because genetic and environmental factors

collectively influence phenotype
Fig. 14-14
 Epistasis

• In epistasis, a gene at one locus alters the

phenotypic expression of a gene at a second locus
• For example, in mice and many other mammals,
coat color depends on two genes
• One gene determines the pigment color (with
alleles B for black and b for brown)
• The other gene (with alleles C for color and c for no
color) determines whether the pigment will be
deposited in the hair
Fig. 14-12


BbCc BbCc

Sperm
1/ 1/ 1/ 1/
4 BC 4 bC 4 Bc 4 bc
Eggs
1/
4 BC
BBCC BbCC BBCc BbCc
1/
4 bC
BbCC bbCC BbCc bbCc
1/
4 Bc
BBCc BbCc BBcc Bbcc
1/
4 bc
BbCc bbCc Bbcc bbcc

9 : 3 : 4
 Pleiotropy

• Most genes have multiple phenotypic effects, a

property called pleiotropy
• For example, pleiotropic alleles are responsible for
the multiple symptoms of certain hereditary
diseases, such as cystic fibrosis and sickle-cell
disease

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

 Pleiotropy
• A gene that affects many
phenotypes is pleiotropic.

• Mutations in the
phenylketonuria gene cause
mental impairment, light hair
color, and the presence of
metabolites in blood and urine.

• Mutations in the Drosophila

singed gene affect bristle shape
and egg production.
 Polygenic Inheritance

• Quantitative characters are those that vary in the

population along a continuum
• Quantitative variation usually indicates polygenic
inheritance, an additive effect of two or more
genes on a single phenotype
• Skin color in humans is an example of polygenic
inheritance
Fig. 14-13

AaBbCc AaBbCc
Sperm
1/ 1/ 1/ 1/ 1/ 1/ 1/ 1/
8 8 8 8 8 8 8 8

1/
8
1/
8
1/
8
1/
8
Eggs
1/
8
1/
8
1/
8
1/
8

Phenotypes: 1/
64
6/
64
15/
64
20/
64
15/
64
6/
64
1/
64
Number of
dark-skin alleles: 0 1 2 3 4 5 6
 Key Points
• Gene action is affected by biological and physical
factors in the environment.
• Two or more genes may influence a trait.
• A gene is pleiotropic if it influences many different
phenotypes.
Consanguinous Matings and Recessive
Traits

Inbreeding
Inbreeding increases the frequency of homozygotes and
decreases the frequency of heterozygotes.
 The Chromosome Theory of
Heredity
Studies on the inheritance of a sex-linked trait
in Drosophila provided the first evidence that
the meiotic behavior of chromosomes is the
basis for Mendel’s Principles of Segregation
and Independent Assortment.
→

¥¥
✗ wt
1
✗✗ wtw ✗ wty

-
 Nondisjunction as Proof of the
Chromosome Theory of Heredity
The Principle of Segregation
The Principle of Independent Assortment
 Sex-Linked Genes in
Human Beings
X- and Y-linked genes have been
studied in humans.
An X-Linked Recessive Disorder:
Hemophilia
*
Calculating the Risk of Inheriting an X-Linked

÷
Disorder: Colorblindness
The Y Chromosome
Pseudo autosomal

region • Few genes on the Y

E-
centromere
chromosome
• Few Y-linked traits

• Pseudoautosomal
genes are on both the
X and Y chromosomes
 Sex Chromosomes and
Sex Determination
In some organisms, chromosomes—
in particular, the sex chromosomes—

⇒
determine male and female
phenotypes.
Sex Determination in Human Beings:
The Presence the Y Chromosome
TDF : testis -

determining
factor
 The SRY gene and the
Testis-Determining Factor (TDF)
Testicular Feminization
◦
-
 Key Points
• In humans sex is determined by a dominant effect of the SRY

% =
gene on the Y chromosome; the product of this gene, the
testis-determining factor (TDF), causes a human embryo to
develop as a male.
• In Drosophila, sex is determined by the ratio of X
chromosomes to sets of autosomes (X:A).
• In honeybees, sex is determined by the number of
chromosome sets; haploid embryos develop into males and
diploid embryos develop into females.
Mechanisms of Dosage Compensation
⇒
• Hyperactivation of X-linked genes in males
(Drosophila)
• Inactivation of one copy of X-linked genes in
females (mammals)
• Downregulation of X-linked genes in females
(Caenorhabditis elegans)
X Inactivation
The Barr Body
 X inactivation in Female Mammals

• In mammalian females
– One of the two X chromosomes in each cell is
randomly@ inactivated duringC-
embryonic)
development
• If a female is heterozygous for a particular gene -

located on the X chromosome

– She will be a mosaic for that character

Two cell populations

in adult cat:

Active X

Early embryo: Orange

X chromosomes fur
Cell division
and X Inactive X
chromosome Inactive X
inactivation
Black
fur

Allele for Active X

black fur
Figure 15.11
Mosaicism

O
 Key Points
• In mammals, dosage compensation for X-
linked genes is achieved by inactivating one of
the two X chromosomes in females.
 Linked Genes Do Not
Assort Independently

Linkage, Recombination, and

Crossing Over
Genes that are on the same chromosome
travel through meiosis together; however,
alleles of chromosomally linked genes can
be recombined by crossing over.
 The haploid cells contain
the same combination of
alleles as the original
chromosomes

The arrangement of linked

alleles has not been altered

Figure 5.1
5-6
 These haploid cells contain a
combination of alleles NOT
found in the original
chromosomes
This new combination of
These are alleles is a result of
termed genetic recombination
parental or These are termed
non- nonparental or recombinant
recombinant cells
cells

Figure 5.1
5-7
Crossing Over
 Multiple
Crossovers
Chromosome 9 in Maize
Evidence that Crossing Over Causes
Recombination
 Key Points
• Linkage between genes is detected as a deviation
from expectations based on Mendel’s Principle of
Independent Assortment.

• The frequency of recombination measures the

intensity of linkage. In the absence of linkage, this
frequency is 50 percent; for very tight linkage, it is
close to zero.
 Key Points
• Recombination is caused by a physical exchange between
paired homologous chromosomes early in prophase of the
first meiotic division after chromosomes have duplicated.

• At any one point along a chromosome, the process of

exchange (crossing over) involves only two of the four
chromatids in a meiotic tetrad.

• Late in prophase I, crossovers become visible as chiasmata.

 Chromosome Mapping

Linked genes can be mapped on a

chromosome by studying how often
their alleles recombine.
Genetic Map Distances

• The distance between

two points on the
genetic map of a
chromosome is the
average number of
crossovers between
them.
 Genetic map usage
overall complexity and evolutionary
genetic organization Gene cloning relationships among
of a particular species different species

Diagnose & treatment Agriculture improvement-

Prediction of inherited
of human disease specific strain & breeding
disease

Estimation of
relative distances Agriculture
between linked improvement-
genes-crossing specific strain &
over breeding
Fig. 15-11

RESULTS
Recombination
frequencies
9% 9.5%
Chromosome
17%

b cn vg
 Mapping the Distance Between
Genes Using Recombination Data-
Alfred Sturtevant
Experimentally, the percentage of recombinant offspring is
correlated with the distance between the two genes
– If the genes are far apart → many recombinant offspring
– If the genes are close → very few recombinant offspring

• Map distance =

Number of recombinant offspring X 100

Total number of offspring

◼ The units of distance are called map units (mu)

indicate relative distance and order, not precise locations of genes

◼ One map unit is equivalent to 1% recombination frequency

◼ They are also referred to as centiMorgans (cM)

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
EXAMPLE
• Genetic mapping accomplished by carrying out a testcross
– A mating between an individual that is heterozygous for two or more
genes and one that is homozygous recessive for the same genes

• Figure 5.9 provides an example of a testcross

– This cross concerns two linked genes affecting bristle length and
body color in fruit flies

◼ s = short bristles ◼ e = ebony body color

◼ s+ = normal bristles ◼ e+ = gray body color

◼ One parent displays both recessive traits

◼ It is homozygous recessive for the two genes (ss ee)
◼ The other parent is heterozygous for the two genes
◼ The s and e alleles are linked on one chromosome
◼ The s+ and e+ alleles are linked on the homologous chromosome

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
 Chromosomes are
the product of a
crossover during
meiosis in the
heterozygous parent

Recombinant
offspring are fewer
in number than
nonrecombinant
offspring

Figure 5.9
5-47
• The data at the bottom of Figure 5.9 can be used to estimate the distance between the two
genes

• Map distance =

Number of recombinant offspring X 100

Total number of offspring

76 + 75
= X 100
542 + 537 + 76 + 75

= 12.3 map units

◼ Therefore, the s and e genes are 12.3 map units apart

from each other along the same chromosome

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
The Data-recombinant frequencies to make
linkage map of fruit fly genes
Alleles Number Percent
Concerne Recombinant/ Recombinant
d Total Number Offspring
y and w/w- 214/21,736 1.0
e
y and v 1,464/4,551 32.2
y and r 115/324 35.5
y and m 260/693 37.5
w/w-e and 471/1,584 29.7
v
w/w-e and 2,062/6,116 33.7
r
w/w-e and 406/898 45.2
m
v and r 17/573 3.0
v and m 109/405 26.9
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
5-53
◼ A close look at Sturtevant’s data reveals two points
that do not agree very well with his genetic map
◼ The y and m dihybrid cross yielded 37.5% recombinants
◼ But the map distance is 57.6

◼ The w and m dihybrid cross yielded 45.2% recombinants

◼ But the map distance is 56.6

◼ So what’s up?
◼ As the percentage of recombinant offspring approaches a
value of 50% :-
◼ The likelihood of multiple crossovers increases

◼ Even numbers of crossover won’t be seen as recombination

◼ So the observed recombinations tend to underestimate
the actual measure of map distance
◼ Refer to Figure 5.11
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
5-57
 Figure 5.11

◼ Multiple crossovers set a quantitative limit on measurable

recombination frequencies as the physical distance increases
◼ A testcross is expected to yield a maximum of only 50%

recombinant offspring

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
5-58
The frequency of recombination
measures the intensity of linkage. In
the absence of linkage, this frequency
is 50 percent; for very tight linkage, it is
close to zero.
Unusual forms of inheritance
1. Maternal effect and epigenetic inheritance
• Involve genes in the nucleus
2. Extranuclear inheritance
• Involves genes in organelles other than the nucleus
– Mitochondria
– Chloroplasts

3. Imprinting

4.

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
7-3
 1. MATERNAL EFFECT
• Maternal effect refers to an inheritance pattern for
certain nuclear genes in which the genotype of
the mother directly determines the phenotype of
her offspring
• Surprisingly, the genotypes of the father and
offspring themselves do not affect the phenotype of
the offspring

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
7-4
 Example
• 1920s by A. E. Boycott on water snail,
Limnaea peregra
– the shell and internal organs can be arranged in one
of two directions
• Right-handed (dextral)
• Left-handed (sinistral)
• The dextral orientation is more common and dominant
 Reciprocal cross

A 3:1 phenotypic ratio would

be predicted by a Mendelian
pattern of inheritance

Figure 7.1
7-6
◼ Alfred Sturtevant later explained the incongruity with Mendelian
inheritance
◼ Snail coiling is due to a maternal effect gene that exists as dextral

(D) and sinistral (d) alelles

◼ The phenotype of the offspring depended solely on the genotype of

the mother

◼ The genotypes of the father and offspring do not affect the

phenotype of the offspring
◼ Epigenetic inheritance refers to a pattern in which a modification
ccurs to a nuclear gene or chromosome that alters gene expression

◼ Epigenetic changes are caused by DNA and chromosomal modifications

◼ These can occur during oogenesis, spermatogenesis or early
embryonic development

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
 2. Mitochondria
• maternally inherited transmission occurs when the defective
gene is encoded in the mitochondrial genome
• MERFF: mitochondrial myoclonus epilepsy with ragged red
fibers
• Kearns-Sayre syndrome
• MELAS:mitochondrial myopathy/encephalopahty /lactic-
acidosis/stroke like episodes
• Mutations in mitochondrially encoded tRNA molecule
 3. Genomic Imprinting
◼ Genomic imprinting is a phenomenon in which
expression of a gene depends on whether it is
inherited from the male or the female parent

◼ Imprinted genes follow a non-Mendelian pattern of

inheritance
◼ Depending on how the genes are “marked”, the offspring
expresses either the maternally-inherited or the
paternally-inherited allele
◼ Not both
◼ This is termed monoallelic expression
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
7-39
◼ Let’s consider the following example in mice:
◼ The Igf-2 gene encodes a growth hormone called insulin-
like growth factor 2
◼ A functional Igf-2 gene is necessary for a normal size

◼ Imprinting results in the expression of the paternal but

not the maternal allele
◼ The paternal allele is transcribed into RNA
◼ The maternal allele is not transcribed

◼ Igf-2m is a mutant allele that yields a partially defective

protein
◼ This may cause a mouse to be dwarf depending on whether it
inherits the mutant allele from its father or mother
◼ Refer to Figure 7.9

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
7-40
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
7-41
Both male and female
mice express the Igf2
in their somatic cells

Male mouse transmits

transcriptionally active
Female mouse alleles
transmits
transcriptionally Transcribed into mRNA
inactive alleles in the somatic cells of
offspring; But yields
defective proteins

Figure 7.10
7-43
◼ Thus genomic imprinting is permanent in the somatic
cells of an animal
◼ However, the marking of alleles can be altered from
generation to generation
◼ Genomic imprinting occurs in several species
including mammals, insects and plants

◼ It may involve
◼ A single gene
◼ A part of a chromosome
◼ An entire chromosome
◼ Even all the chromosomes from one parent
◼ It can be used for X inactivation in some species
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
7-44
 Imprinting
• Inheritance of a trait occurs only from one parent.
• The particular gene is only expressed from either maternally or paternally
inherited allele.
• The chosen parental allele is constant from one person to the next for all of
the few, known imprinted genes.
• A process that alters the state of a gene without altering its nucloetide
sequence; often associate with methylation of specific nucleotides . The
altered state is established in the germ line and is transmitted to the
offspring where it may persists through offspring’s life.
• Prader-Willi & Angelman syndrome are well known examples of diseases that
result from oppositely imprinted genes in the same region of chromosome
15.
• DNA methylation involves the addition of a methyl group to
the 5 position of the cytosine pyrimidine ring or the number 6
nitrogen of the adenine purine ring (cytosine and adenine are
two of the four bases of DNA).
• alters the gene expression pattern in cells such that cells can
"remember where they have been" or decrease gene
expression