Download Multigenic determination of behavioral traits Tourette`s Disorder In a

Genetics and Human Behavior
Abu-isliah nabhan
Consultant psychiatrist
Introduction
The human genome consists of between 30.000
and 50.000 genes of which over 20.000 have
been identified
Over 5.000 genetic disorders transmitted
through single mutated gene have been
characterized
Maps of human genomes permitted localization
to chromosomal regions of over 400 of disease
genes
Linkage Analysis or Positional
Cloning
Mapping genes essentially involves correlating
the inheritance the trait with the inheritance of
molecular markers scattered throughout an
animal’s genetic material
The site of the chromosome where gene is
located called locus
The Genetics of Behavior



19th century monk Gregory Mendel
demonstrated that inheritance occurs
through genes.
Genes are basic units of heredity that
maintain their structural identity from
one generation to another.
Genes are aligned along chromosomes
(strands of genes) and come in pairs.
The Genetics of Behavior


A gene is a portion of a chromosome and
is composed of deoxyribonucleic acid
(DNA).
DNA serves as a model for the synthesis
of ribonucleic acid (RNA).
Fig. 1-7, p. 12
The Genetics of Behavior


RNA is a single strand chemical that
can serve as a template/ model for the
synthesis of proteins.
Proteins determine the development of
the body by:
•
•
forming part of the structure of the body.
serving as enzymes that serve as
biological catalysts and regulate chemical
reaction in the body.
The Genetics of Behavior


Homozygous for a gene means that a
person has an identical pair of genes on
the two chromosomes.
Heterozygous for a gene means that a
person has an unmatched pair of genes
on the two chromosomes.
The Genetics of Behavior

Some genes can be either dominant
or recessive.



Examples: eye color, ability to taste
A dominant gene shows a strong
effect in either the homozygous or
heterozygous condition.
A recessive gene shows its effect only
in the homozygous condition.
Fig. 1-8, p. 13
The Genetics of Behavior



Each chromosome participates in
reproduction independently of the
others.
Each species has a certain number of
chromosomes.
Crossing over occurs when a pair of
chromosomes break apart during
reproduction and reconnects and
attaches to the second chromosome.
The Genetics of Behavior

Types of genes include:



Autosomal genes - all genes except for
sex- linked genes.
Sex-linked genes - genes located on the
sex chromosomes.
In mammals, the sex chromosomes are
designated X & Y.


Females have two X chromosomes (XX).
Males have an X and a Y chromosome
(XY).
The Genetics of Behavior

During reproduction:




Females contribute an X chromosome.
Males contribute either an X or a Y
chromosome that determines the sex of
the child.
If an X chromosome is contributed by
the male, the off-spring is female.
If a Y chromosome is contributed by the
male, the off-spring will be male.
The Genetics of Behavior




The human Y chromosome has genes
for 27 proteins
The human X chromosome has genes
for approximately 1500 proteins.
Thus, sex-linked genes usually refer to
X-linked genes. (Example: Red-green
color deficiency)
Sex-limited genes are genes that are
present in both sexes but mainly have
The Genetics of Behavior



Sources of variation in a species that
allows for evolution to occur include:
Recombination refers to a new
combination of genes in the off-spring
that yield characteristics not found in
either parent.
Mutation refers to a change in a single
gene that is rare, random and often
independent of the needs of the
The Genetics of Behavior



Almost all behaviors have both a
genetic component and an
environmental component.
Researchers study monozygotic and
fraternal twins to infer how much of a
genetic component exists for a
particular behavior.
Researchers also study adopted
children and their resemblance to their
The Genetics of Behavior


Estimates of hereditary influences are
often difficult to infer and are prone to
error.
Sources of error include the following:


The inability to distinguish between the effects
of genes and prenatal influences.
Environmental factors can inactivate genes.
The Genetics of Behavior

Sources of error (con’t)


Multiplier effect – genetic tendencies that
guide behavior will result in a change in the
environment that magnifies the original
tendency.
Traits with a strong hereditary influence
can by modified by environmental
intervention.

Eg. “elevated plus maze”, PKU
The Genetics of Behavior



Genes do not directly produce behaviors.
Genes produce proteins that increase the
probability that a behavior will develop
under certain circumstances.
Genes can also have an indirect affect.

Genes can alter your environment by
producing behaviors or traits that alter how
people in your environment react to you.
The Genetics of Behavior


Evolution refers to a change in the
frequency of various genes in a
population over generations
Evolution attempts to answer two
questions:
1.
2.
How did some species evolve?
How do species evolve?
The Genetics of Behavior


How species did evolve involves the
tentative construction of “evolutionary
trees”.
How species do evolve rests upon two
assumptions:
1.
2.
Offspring generally resemble their
parents for genetic reasons.
Mutations and recombination of genes
introduce new heritable variations that
help or harm the chance of survival and
reproduction.
Fig. 1-10, p. 17
The Genetic of Behavior

Common misconceptions about
evolution include the following:




Lamarckian evolution - “The use or disuse
of some structure or behavior causes an
increase or decrease in that behavior.”
“Humans have stopped evolving.”
“Evolution means improvement.”
“Evolution acts to benefit the individual or
the species.”
The Genetics of Behavior


Evolutionary psychology (sociobiology)
focuses upon functional explanations of
how behaviors evolved.
Assumes that behaviors characteristic
of a species have arisen through natural
selection and provide a survival
advantage.

Examples: differences in peripheral/color
vision, sleep mechanisms in the brain,
eating habits, temperature regulation.
The Genetics of Behavior


Some behaviors are more debatable
regarding the influence of natural
selection.
Examples include:



Life span length
Gender differences in sexual promiscuity
Altruistic behavior
The Use of Animals in Research


Animal research is an important source of
information for biological psychology but
remains a highly controversial topic.
Animal research varies on the amount of
stress and/ or pain that is caused to the
animal itself.
The Use of Animals in Research

Reasons for studying animals include:
1.
2.
3.
4.
The underlying mechanisms of behavior
are similar across species and often
easier to study in nonhuman species.
We are interested in animals for their own
sake.
What we learn about animals sheds light
on human evolution.
Some experiments cannot use humans
because of legal or ethical reasons.
The Use of Animals in Research

Opposition to animal research varies:


“Minimalists” favor firm regulation on
research and place consideration upon the
type of animal used and the amount of
stress induced.
“Abolitionists” maintain that all animals
have the same rights as humans and any
use of animals is unethical.
The Use of Animals in Research

Justification for research considers the
amount of benefit gained compared to
the amount of distress caused to the
animal.


No clear dividing line exists.
Colleges and research institutions in the
United States are required to have an
Institutional Animal Care and Use
Committee.
Traits determined by single genes
Autosomal dominant
Autosomal recessive
X-linked recessive
Genetics of Psychiatry
Hurdles of Assigning behavioral Traits to
Specific Genes
•Categorization of most psychiatric disorders includes
genetically heterogeneous population of patients
•Lack of quantifiable tests for psychiatric disorders
•Familial clustering of certain behavioral traits can be
due to either genetics (nature) or upbringing (nurture)
•Multigenic determination of behavioral traits
Tourette’s Disorder
In a several family pedigrees the disorder is
transmitted as autosomal dominant mode with
penetrance of 99% in males and 70% in females
Screening almost all chromosomes failed to
identify a specific genetic locus always inherited
with the clinical behavior
This finding suggest that Tourette’s syndrome is
A multigenic trait
Bipolar Disorder
A locus that confers increased risk of bipolar
disorder, has been identified on chromosome 18
base on an analysis of 22 pedigrees but the
correlation is not robust
Basic Molecular Biology
“DNA makes RNA makes protein”
DNA is a genetic code consisting of series of
bases, (A), (C), (G), (T)
Genes consists of a strings of DNA code that
specify series of base triplets called codons that
determine a specific sequence of amino acids
Human genetic material consists of 3 billions
bases of DNA
Chromosome is a unit of 60 million bases
Premises 0f Neurogenetics
A first-degree of an affected schizophrenic
patient has about 10% chance of having the
illness, far in excess of the I% risk in general
population. MZ twins display nearly 50%
concordance for schizophrenia
Bipolar I disorder and major depressive
disorder exhibit similar familial clustering
First degree relatives have 8-18 times
increased risk. MZ:33-90 % concordance
Premises 0f Neurogenetics
Traits are clinically defined features, such as
sickle crises or blue eyes
Some traits are determined by a single gene,
others emerge from the interaction of the
products of hundreds of genes
Behavior likely is the expression of the product
of thousands of genes
Personality Trait of Anxiety
A genetic variant of of the serotonin transporter
gene has been described that alters the number
of the transporter molecules of the presynaptic
membrane of serotonergic neurons
This accounts for 5% of the genetic variance of
anxiety in general population
Schizophrenia
A locus on chromosome 15 appears to account
for auditory processing in several pedigrees of
patients with schizophrenia
A study of 265 Irish families with high incidence
of schizophrenia found two loci, on chromosome
8 and 6. Each of which accounted for the
vulnerability to schizophrenia in 10-30 % of the
families
Alzheimer’s Disease
10% of cases of Alzheimer’s disease are
hereditary and the remaining 90% are sporadic
Of the hereditary cases 70-80% are attributable
to mutations in the presenilin 1 gene located on
chromosome 14. Age of onset: 40-50years
20-30% are attributable to mutations in the
presenilin 2 located on chromosome 1.
Age of onset: 50years
Alzheimer’s Disease
2-3% of the familial cases are attributable to
mutations in the B-amyloid precursor protein
(APP) gene located on chromosome 21, which
causes the symptoms at the age of 50 years
Animal Models of Human
Behavior
•Some genes have been assumed to encode
proteins needed for behavior such as
neurotransmitter receptors
•Knockout technology : Methods of gene
targeting which can assess the contribution of
specific candidate genes to mouse behavior
Animal Models of Human
Behavior
•Gene targeting allows the creation of mice with
deletion or modification of specific candidate
gene
Phenotypes of mutant mice:
•No detectable behavioral abnormalities because
the gene is redundant
•Some gene knockouts are lethal in the embryo
•The mutant animals display specific abnormal
behavior
New Methods for Isolation of Human Genes
Responsible for Behavioral Traits
DNA microassays allow to study the regulation
of several genes in a single experiment. This
method can potentially link specific clinical
manifestations of psychiatric disorders to the
expression of relevant genes
The field of Pharmacogenomics focuses on the
genetic determinant of drug response at the level
of the entire genome
Method of study in Psychiatric
Genetics
Twin studies
MZ twins are the product of the division of
single fertilized ovum and therefore genetically
identical.
DZ twins are the result of near simultaneous
fertilization and implantation of two separate
ova and like full siblings have an average of
50% of their genes in common
Method of study in Psychiatric
Genetics
Twin studies
High MZ concordance rates do not necessarily
reflect a genetic aetiology
It is the ratio of the MZ:DZ concordance rates
that indicates the extent of genetic contribution
Any difference within MZ pairs is almost
certainly non-genetic, so that studies of
discordant patients can provide evidence of
environmental aetiological factors
Adoption studies
Type of study
Adoptee
study
Adoptee family
study
Cross-fostering
study
who is studied
Adopted –away
offspring of
patients
comparisons made
Rate of illness
versus rate in
control adoptees
Biological and Rate in biological
adopted relatives Vs Adoptive rela
Individuals with
ill biological,
raised by healthy
adoptive parent
Individuals with
vice versa
Rate of illness
in two types of
adoptees
Life Time Expectancy of Schizophrenia in
the Relative of Schizophrenics
Gottesman& Shields (1982)
Relationships
Parent
Sibling
Sibling (one parent is affected)
Children
Children (both parents affected)
Uncles/aunts/nephews/nieces
Grandchildren
Unrelated
Percentage
Schizophrenic
5.6
10.1
16.7
12.8
46.3
2.8
3.7
0.86
Patterns of Inheritance
Genotype: genetic constitution
Phenotype: Physical appearance
Single Locus Inheritance: A continuous
distribution of a genetic character can
sometimes be due to two alleles at one locus
Polygenic Inheritance: When the inherited
characteristics are due to the combined
effect of many genes at different loci acting
additively
Patterns of Inheritance
Multifactorial:Liability/threshold: the liability
to inherit the characteristics is composed of the
mainly additive effects of many genes at
different loci together with environmental
effects
Partial Peneterance: when the diseased gene is
dominant and only a proportion of
heterzygotes show signs of disease due to
environmental influence
Linkage studies
The co-segregation of a marker and a disease is
investigated within families
A marker allele and the disorder are coinherited within pedigrees at higher frequency
than would be expected by chance
This occurs when the two loci are close together
on same chromosome
Recombinant and Recombination Fraction
Parental gametes
AB
ab
Offspring genotype
AaBb
Offspring gametes
AB ab
Ab aB
Parental type
recombinant
gametes
gametes
recombinant gametes
Recombination Fraction=
number of gametes
Recombinant and Recombination Fraction
When recombination fraction is ½ ; at this value
the genes at the two loci segregate
independently
If the recombination fraction is <½ , then the
two loci must be on the same chromosome, and
are said to be linked
Selfish Gene
The followings are true regarding selfish gene
except:
a. It programmes us not to be selfish
b. A term coined by Richard Dawkin
c. A term comes from social psychiatry
d. It reflects natural selection
e. It indicates that the organism sacrifice life for
relatives to protect its gene