Genetics and Human Behavior Abu-isliah nabhan Consultant psychiatrist Genetics and Human Behavior...

Genetics and Human Behavior

Abu-isliah nabhanConsultant psychiatrist

Genetics and Human Behavior

Abu-isliah nabhanConsultant psychiatrist

Introduction

The human genome consists of between 30.000 and 50.000 genes of which over 20.000 have been identifiedOver 5.000 genetic disorders transmitted through single mutated gene have been characterizedMaps of human genomes permitted localization to chromosomal regions of over 400 of disease genes

Introduction

The human genome consists of between 30.000 and 50.000 genes of which over 20.000 have been identifiedOver 5.000 genetic disorders transmitted through single mutated gene have been characterizedMaps 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

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.


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


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.


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.


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


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


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).


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 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.)


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.


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.

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.


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


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.


Evolution refers to a change in the frequency of various genes in a population over generations

Evolution attempts to answer two questions:1. How did some species evolve?

2. How do species evolve?



How species did evolve involves the tentative construction of “evolutionary trees”.

How species do evolve rests upon two assumptions:

1. Offspring generally resemble their parents for genetic reasons.

2. 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.”


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.


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.


Reasons for studying animals include:1. The underlying mechanisms of behavior

are similar across species and often easier to study in nonhuman species.

2. We are interested in animals for their own sake.

3. What we learn about animals sheds light on human evolution.

4. Some experiments cannot use humans because of legal or ethical reasons.


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.


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.

Traits determined by single genes

Autosomal dominant

Autosomal recessive

X-linked recessive

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

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 behaviorThis finding suggest that Tourette’s syndrome isA multigenic trait

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 behaviorThis finding suggest that Tourette’s syndrome isA 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

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 acidsHuman genetic material consists of 3 billions bases of DNAChromosome is a unit of 60 million bases

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 acidsHuman genetic material consists of 3 billions bases of DNAChromosome 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 schizophreniaBipolar I disorder and major depressive disorder exhibit similar familial clusteringFirst degree relatives have 8-18 times increased risk. MZ:33-90 % concordance


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 schizophreniaBipolar I disorder and major depressive disorder exhibit similar familial clusteringFirst degree relatives have 8-18 times increased risk. MZ:33-90 % concordance


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


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 neuronsThis accounts for 5% of the genetic variance of anxiety in general population

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 neuronsThis 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

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 sporadicOf the hereditary cases 70-80% are attributable to mutations in the presenilin 1 gene located on chromosome 14. Age of onset: 40-50years20-30% are attributable to mutations in the presenilin 2 located on chromosome 1.Age of onset: 50years


10% of cases of Alzheimer’s disease are hereditary and the remaining 90% are sporadicOf the hereditary cases 70-80% are attributable to mutations in the presenilin 1 gene located on chromosome 14. Age of onset: 40-50years20-30% are attributable to mutations in the presenilin 2 located on chromosome 1.Age of onset: 50years


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


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 asneurotransmitter receptors•Knockout technology : Methods of gene targeting which can assess the contribution of specific candidate genes to mouse behavior


•Some genes have been assumed to encode proteins needed for behavior such asneurotransmitter receptors•Knockout technology : Methods of gene targeting which can assess the contribution of specific candidate genes to mouse behavior


•Gene targeting allows the creation of mice with deletion or modification of specific candidate genePhenotypes 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


•Gene targeting allows the creation of mice with deletion or modification of specific candidate genePhenotypes 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

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 studiesMZ 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


Twin studiesMZ 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


Twin studiesHigh 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 contributionAny difference within MZ pairs is almost certainly non-genetic, so that studies of discordant patients can provide evidence of environmental aetiological factors


Twin studiesHigh 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 contributionAny difference within MZ pairs is almost certainly non-genetic, so that studies of discordant patients can provide evidence of environmental aetiological factors

Adoption studiesType of study who is studied comparisons made

Adoption studiesType 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

Life Time Expectancy of Schizophrenia in the Relative of Schizophrenics

Gottesman& Shields (1982)

Relationships PercentageSchizophrenic

Parent 5.6Sibling 10.1Sibling (one parent is affected) 16.7Children 12.8Children (both parents affected) 46.3Uncles/aunts/nephews/nieces 2.8Grandchildren 3.7Unrelated 0.86

Life Time Expectancy of Schizophrenia in the Relative of Schizophrenics

Gottesman& Shields (1982)

Relationships PercentageSchizophrenic

Parent 5.6Sibling 10.1Sibling (one parent is affected) 16.7Children 12.8Children (both parents affected) 46.3Uncles/aunts/nephews/nieces 2.8Grandchildren 3.7Unrelated 0.86

Patterns of Inheritance

Genotype: genetic constitutionPhenotype: Physical appearanceSingle Locus Inheritance: A continuous distribution of a genetic character can sometimes be due to two alleles at one locusPolygenic Inheritance: When the inherited characteristics are due to the combined effect of many genes at different loci acting additively


Genotype: genetic constitutionPhenotype: Physical appearanceSingle Locus Inheritance: A continuous distribution of a genetic character can sometimes be due to two alleles at one locusPolygenic Inheritance: When the inherited characteristics are due to the combined effect of many genes at different loci acting additively


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 effectsPartial Peneterance: when the diseased gene is dominant and only a proportion of heterzygotes show signs of disease due to environmental influence


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 effectsPartial 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 familiesA marker allele and the disorder are co-inherited within pedigrees at higher frequency than would be expected by chanceThis occurs when the two loci are close together on same chromosome

Linkage studies

The co-segregation of a marker and a disease is investigated within familiesA marker allele and the disorder are co-inherited within pedigrees at higher frequency than would be expected by chanceThis occurs when the two loci are close together on same chromosome

Recombinant and Recombination Fraction

Parental gametes AB abOffspring genotype AaBbOffspring gametes AB ab Ab aB

Parental type recombinant gametes gametes

recombinant gametesRecombination Fraction=

number of gametes


Parental gametes AB abOffspring genotype AaBbOffspring gametes AB ab Ab aB

Parental type recombinant gametes gametes

recombinant gametesRecombination Fraction=

number of gametes


When recombination fraction is ½ ; at this value the genes at the two loci segregate independentlyIf the recombination fraction is <½ , then the two loci must be on the same chromosome, and are said to be linked


When recombination fraction is ½ ; at this value the genes at the two loci segregate independentlyIf 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 selfishb. A term coined by Richard Dawkinc. A term comes from social psychiatryd. It reflects natural selectione. It indicates that the organism sacrifice life

for relatives to protect its gene

Selfish Gene

The followings are true regarding selfish gene except:

a. It programmes us not to be selfishb. A term coined by Richard Dawkinc. A term comes from social psychiatryd. It reflects natural selectione. It indicates that the organism sacrifice life

for relatives to protect its gene

Genetics and Human Behavior Abu-isliah nabhan Consultant psychiatrist Genetics and Human Behavior...

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