Genetics and Human Behavior

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Genetics and Human Behavior Abu-isliah
nabhan Consultant psychiatrist
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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
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Linkage Analysis or Positional Cloning Mapping
genes essentially involves correlating the
inheritance the trait with the inheritance of
molecular markers scattered throughout an
animals genetic material The site of the
chromosome where gene is located called locus
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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.

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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).

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Fig. 1-7, p. 12
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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.

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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.

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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.

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Fig. 1-8, p. 13
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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.
• BC bc ? Bc bC

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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).

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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.

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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 an effect on one sex
  (Chest hair, breast size, etc.)

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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 organism.

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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 biological parents to infer
  the influence of heredity.

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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.

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The Genetics of Behavior

• Sources of error (cont)
• 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

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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.

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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
• How did some species evolve?
• How do species evolve?

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The Genetics of Behavior

• How species did evolve involves the tentative
  construction of evolutionary trees.
• How species do evolve rests upon two assumptions
• 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.

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Fig. 1-10, p. 17
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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.

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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.

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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

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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.

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The Use of Animals in Research

• Reasons for studying animals include
• 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.

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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.

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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.
• Oversees and determine acceptable procedures.

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Traits determined by single genes Autosomal
dominant Autosomal recessive X-linked
recessive
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• 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

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Tourettes 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 Tourettes
syndrome is A multigenic trait
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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
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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
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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. MZ33-90 concordance
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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
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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
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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
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Alzheimers Disease 10 of cases of Alzheimers
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
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Alzheimers 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
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• 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

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• 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

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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
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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
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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 MZDZ 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
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Adoption studies Type of study who is
studied comparisons made
Adoptee study Adopted away offspring of patients Rate of illness versus rate in control adoptees
Adoptee family study Biological and adopted relatives Rate in biological Vs Adoptive rela
Cross-fostering study Individuals with ill biological, raised by healthy adoptive parent Individuals with vice versa Rate of illness in two types of adoptees
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Life Time Expectancy of Schizophrenia in the
Relative of Schizophrenics Gottesman Shields
(1982) Relationships Percentage Schizophr
enic Parent 5.6 Sibling 10.1 Sibling
(one parent is affected) 16.7 Children 12.8
Children (both parents affected) 46.3 Uncles/aunt
s/nephews/nieces 2.8 Grandchildren 3.7 Unrel
ated 0.86
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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
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Patterns of Inheritance MultifactorialLiability/
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
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Linkage studies The co-segregation of a marker
and a disease is investigated within families A
marker allele and the disorder are co-inherited
within pedigrees at higher frequency than would
be expected by chance This occurs when the two
loci are close together on same chromosome
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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
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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 lt½ , then the two
loci must be on the same chromosome, and are said
to be linked
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• Selfish Gene
• The followings are true regarding selfish gene
  except
• It programmes us not to be selfish
• A term coined by Richard Dawkin
• A term comes from social psychiatry
• It reflects natural selection
• It indicates that the organism sacrifice life for
  relatives to protect its gene