This document discusses genetics and psychobiology. It covers topics such as psychiatric genetics, the human genome project, DNA, genes, chromosomes, genetic variation, and heritability. The key points are:
- Psychiatric genetics studies the role of genetics in psychological conditions like schizophrenia and aims to improve treatment and develop personalized treatments.
- The human genome contains 3 billion base pairs organized into 23 chromosome pairs in most cells. The genome project mapped the entire human genome sequence.
- Genes hold the information to build proteins and traits that are passed down. Many psychological conditions like schizophrenia and bipolar disorder show genetic influences through family and twin studies. However, the genetics are complex with most having multiple genetic and environmental factors.
These slides,describes the general and possible causes of mental disorders.
These slides can be used by Psychiatric students,mental health nurses,Doctors and clinical officer students including whoever interested in mental disorders etiology.
These slides,describes the general and possible causes of mental disorders.
These slides can be used by Psychiatric students,mental health nurses,Doctors and clinical officer students including whoever interested in mental disorders etiology.
Concept of Neurosis and Psychosis. Differences between these psychiatric disorders. It is an important topic for students belongs disciplines such as psychiatry, psychology, psychiatric nursing and psychiatric social work.
Concept of Neurosis and Psychosis. Differences between these psychiatric disorders. It is an important topic for students belongs disciplines such as psychiatry, psychology, psychiatric nursing and psychiatric social work.
-Basic Concepts in Genetics
-What is Epigenetic?
-History of Epigenetic
-How do epigenetics work?
-Epigenetics and the Environment
-Epigenetic Inheritance
-Epigenetics in Psychiatry
Epigenetics is the study, in the field of genetics, of cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence. -Wikipedia
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2. Introduction
• Psychiatric genetics, a subfield of behavioral
neurogenetics, studies the role of genetics in psychological
conditions such as alcoholism, schizophrenia, bipolar
disorder, and autism
• Psychiatric genetics is a somewhat new name for an old
question, "Are behavioral and psychological conditions and
deviations inherited". The goal of psychiatric genetics is to
better understand the etiology of psychiatric disorders, to
use that knowledge to improve treatment methods, and
possibly also to develop personalized treatments based on
genetic profiles.
• In other words, the goal is to transform parts of psychiatry
into a neuroscience-based discipline.
3. History
• Research on psychiatric genetics began in the late
nineteenth century with Francis Galton (a founder of
psychiatric genetics) who was motivated by the work of
Charles Darwin and his concept of desegregation.
• These methods of study later improved due to the
development of more advanced clinical, epidemiological,
and biometrical research tools.
• Better research tools were the precursor to the ability to
perform valid family, twin, and adoption studies.
Researchers learned that genes influence how these
disorders manifest and that they tend to aggregate in
families.
4. Genome
• The genome is the entirety of an organism's hereditary
information. It is encoded either in DNA or, for many types of
viruses, in RNA. The genome includes both the genes and the
non-coding sequences of the DNA/RNA
• An analogy to the human genome stored on DNA is that of
instructions stored in a book:
• The book (genome) would contain 23 chapters
(chromosomes);
• Each chapter contains 48 to 250 million letters (A,C,G,T)
without spaces;
• Hence, the book contains over 3.2 billion letters total;
• The book fits into a cell nucleus the size of a pinpoint;
• At least one copy of the book (all 23 chapters) is contained in
most cells of our body. The only exception in humans is found
in mature red blood cells which become enucleated during
development and therefore lack a genome.
5. DNA
• Deoxyribonucleic acid (DNA) is a molecule that encodes the
genetic instructions used in the development and functioning of
all known living organisms and many viruses.
• DNA is a nucleic acid; alongside proteins and carbohydrates,
nucleic acids compose the three major macromolecules
essential for all known forms of life. Most DNA molecules are
double-stranded helices, consisting of two long biopolymers
made of simpler units called nucleotides—each nucleotide is
composed of a nucleobase (guanine, adenine, thymine, and
cytosine), recorded using the letters G, A, T, and C, as well as a
backbone made of alternating sugars (deoxyribose) and
phosphate groups (related to phosphoric acid), with the
nucleobases (G, A, T, C) attached to the sugars.
• DNA is well-suited for biological information storage.
•
6.
7. RNA
• Ribonucleic acid (RNA) perform multiple vital roles in the
coding, decoding, regulation, and expression of genes.
• Like DNA, RNA is assembled as a chain of nucleotides, but is
usually single-stranded. Cellular organisms use messenger
RNA (mRNA) to convey genetic information (often notated
using the letters G, A, U, and C for the nucleotides guanine,
adenine, uracil and cytosine) that directs synthesis of specific
proteins, while many viruses encode their genetic information
using an RNA genome.
• Some RNA molecules play an active role within cells by
catalyzing biological reactions, controlling gene expression, or
sensing and communicating responses to cellular signals.
•
8.
9. Gene
• A gene is the molecular unit of heredity of a living
organism.
• Living beings depend on genes, as they specify all
proteins and functional RNA chains.
• Genes hold the information to build and maintain an
organism's cells and pass genetic traits to offspring.
• All organisms have many genes corresponding to various
biological traits, some of which are immediately visible,
such as eye color or number of limbs, and some of which
are not, such as blood type, increased risk for specific
diseases, or the thousands of basic biochemical
processes that comprise life.
10. RNA genes and genomes in the world-
• When proteins are manufactured, the gene is first copied into RNA
as an intermediate product. In other cases, the RNA molecules are
the actual functional products.
• For example, RNAs known as ribozymes are capable of enzymatic
function, and microRNA has a regulatory role. The DNA
sequences from which such RNAs are transcribed are known as
RNA genes.
• Some viruses store their entire genomes in the form of RNA, and
contain no DNA at all. Because they use RNA to store genes, their
cellular hosts may synthesize their proteins as soon as they are
infected and without the delay in waiting for transcription.
• On the other hand, RNA retroviruses, such as HIV, require the
reverse transcription of their genome from RNA into DNA before
their proteins can be synthesized.
• In 2006, French researchers came across a puzzling example of
RNA-mediated inheritance in mice. Mice with a loss-of-function
mutation in the gene Kit have white tails. Offspring of these
mutants can have white tails despite having only normal Kit genes.
The research team traced this effect back to mutated Kit RNA.
11. Chromosomes
• The total complement of genes in an organism or cell is
known as its genome, which may be stored on one or
more chromosomes; the region of the chromosome at
which a particular gene is located is called its locus.
• A chromosome consists of a single, very long DNA helix
on which thousands of genes are encoded.
12. DNA and Human Genome Project
• The history of biology was altered forever by the launching of the Human
Genome Project, a research program that has characterized the
complete set of genetic instructions of the human. Science is showing
that the complexity of human emotions and behaviour is governed by a
variety of genes and their interplay with each other, environmental
factors, personality and life experiences (Cole et al, 2010).
• Determined of the DNA sequence for the human gene was completed in
April 2003, marking the end of the Human Genome Project, 2 years
ahead of schedule. One of the most daunting challenges remaining is
that of understanding how all the parts of cells- genes, proteins and many
other molecules work together to create complex living organisms in
heath and illness (NHGRI, 2011)
• Insights gained from the human DNA sequence:
• The human genome contains 3 billion nucleotide bases (A, C, T, G),
combinations of which comprise all genetic codes. The average gene has
3000 bases. Humans have about 30,000 genes (one third as many as
previously thought), the same number as found in a laboratory mouse.
13. • The functions of more than 50% of the discovered genes are
still unknown,
• The human genome sequence is almost (99%) exactly the
same in all people.
• Slight variations in DNA sequence can have a major impact on
the manifestation of a disease process and on responses to
environmental factors, such as presence of microbes, toxins
and drugs.
• Single-nucleotide polymorphisms (SNPs) are sites in the
human genome where individuals differ in their DNA sequence,
often only by a single base. Sets of SNPs on the same
chromosome are inherited in blocks and may help determine
the etiology of disease as well as the efficacy of new
treatments.
14. • The genome, an organism’s complete set of DNA instructions, is
organized into chromosomes, which contain many genes, the basic
physical and functional units of heredity. Genes are specific sequence
of bases that encode instructions on how to make proteins, which
are large, complex molecules made up of amino acids. It is the
proteins that perform most life functions and constitute the majority of
cellular structures.
• Genetic mapping, also called linkage mapping. It can offer firm
evidence that a disease transmitted from parent to child is linked to
one or more genes, and it provides clues as to which chromosomes
contain the gene and where the gene is on the chromosome.
• Genetic testing is a commercial medical application of the new
genetic discoveries, used to diagnose disease, confirm a diagnosis,
provide prognostic information about the course of a disease, confirm
the existence of a disease in symptomatic individuals, and detect
predispositions to disease in healthy individuals and their offspring.
15. Human genetic variation
• Human genetic variation is the genetic differences both within and
among populations.
• No two humans are genetically identical. Even monozygotic twins,
who develop from one zygote, have infrequent genetic differences
due to mutations occurring during development and gene copy
number variation.
• Differences between individuals, even closely related individuals,
are the key to techniques such as genetic fingerprinting. Alleles
occur at different frequencies in different human populations, with
populations that are more geographically and ancestrally remote
tending to differ more.
• Causes of differences between individuals include the exchange of
genes during meiosis and various mutational events.
16. • There are at least two reasons why genetic variation exists
between populations.
• Natural selection may confer an adaptive advantage to
individuals in a specific environment if an allele provides a
competitive advantage. Alleles under selection are likely to
occur only in those geographic regions where they confer an
advantage.
• The second main cause of genetic variation is due to the high
degree of neutrality of most mutations. Most mutations do not
appear to have any selective effect one way or the other on the
organism. The main cause is genetic drift, this is the effect of
random changes in the gene pool. In humans, founder effect
and past small population size (increasing the likelihood of
genetic drift) may have had an important influence in neutral
differences between populations.
17. • Measures of variation- Genetic variation among humans
occurs on many scales, from gross alterations in the
human karyotype to single nucleotide changes.
• Nucleotide diversity is the average proportion of
nucleotides that differ between two individuals. The
human nucleotide diversity is estimated to be 0.1% to
0.4% of base pairs. A difference of 1 in 1,000 amounts to
approximately 3 million nucleotide differences, because
the human genome has about 3 billion nucleotides.
18. • Single nucleotide polymorphisms- A single nucleotide
polymorphism (SNP) is difference in a single nucleotide
between members of one species that occurs in at least 1% of
the population. It is estimated that there are 10 to 30 million
SNPs in humans.
• SNPs are the most common type of sequence variation,
estimated to comprise 90% of all sequence variations. Other
sequence variations are single base exchanges, deletions and
insertions.
• A functional, or non-synonymous, SNP is one that affects some
factor such as gene splicing or messenger RNA, and so
causes a phenotypic difference between members of the
species. About 3% to 5% of human SNPs are functional.
Neutral, or synonymous SNPs are still useful as genetic
markers in genome-wide association studies, because of their
sheer number and the stable inheritance over generations.
• A coding SNP is one that occurs inside a gene. They occur due
to segmental duplication in the genome. These SNPs result in
loss of protein, yet all these SNP alleles are common and are
not purified in negative selection.
19. Genes, brain, and behaviour:
• Based on family, twin and adoption studies, it is apparent
that both genetic and environmental factors play important
roles in the normal development of temperament,
personality and attitudes as well as in the pathogenesis of
major mental disorders.
• Before the advent of molecular genetics, human
behavioural genetics, including investigations of mental
illness, were limited to quantitative analyses of twin
studies, adoption studies and multigenerational family
designs that attempted to discriminate genetic from
nongenetic influences on behavioural phenotypes and to
determine the modes of inheritance.
20. • The fundamental challenges facing psychiatric genetics
are the difficulty of defining phenotypes and the
apparently large number of genetic and nongenetic risk
factors involved in producing mental illness phenotypes.
Gene-environment interaction may play a role not only in
the initial expression of mental disorders but also in their
course.
21. Heritability and Genetics
• The term genotype refers to the total set of genes
present in an individual at the time of conception, and
coded in the DNA. The physical manifestations of a
particular genotype are designated by characteristics that
specify a specific phenotype.
• Examples of phenotype include eye colour, height, blood
type, and language and hair type.
• As evident by the examples presented, phenotypes are
not only genetic but may also be acquired i.e. influenced
by the environment, or a combination of both. I is likely
that many psychiatric disorders are the result of a
combination of genetics and environmental influences.
22. • Investigators who study the etiological implications for
psychiatric illness may explore several risk factors.
Studies to determine if an illness is familial compare the
percentage of family members with the illness to those in
the general population or within a control group of
unrelated individuals. These studies estimate the
prevalence of psychopathology among relatives, and
make predictions about the predictions about the
predisposition to an illness based on familial risk factors.
•
23. • Schizophrenia, bipolar disorder, major depression,
anorexia nervosa, panic disorder, somatisation disorder,
antisocial personality disorder and alcoholism are
examples of psychiatric illness in which familial
tendencies have been indicated.
• Most psychiatric disorders are highly heritable; the
estimated heritability for bipolar disorder, schizophrenia,
and autism (80% or higher) is much higher than that of
diseases like breast cancer and Parkinson disease.
Having a close family member affected by a mental illness
is the largest known risk factor, to date. However, linkage
analysis and genome-wide association studies have
found few reproducible risk factors.
24. • Studies that are purely genetic in nature search for a specific
gene that is responsible for an individual having a particular
illness. A number of disorders exist in which the mutation of a
specific gene or change in the number or structure of a
chromosome has been associated with the etiology.
• Examples include Huntington’s disease, cystic fibrosis,
phenylketonuria and Down syndrome.
• Heterogeneity is an important factor to consider when dealing
with genetics. Two types of heterogeneity have been identified
in association with psychiatric genetics: causal and clinical.
Causal heterogeneity refers to a situation in which two or more
causes can independently induce the same clinical syndrome.
Clinical heterogeneity refers to when a single cause can lead to
more than one clinical syndrome.
25. • In addition to familial and purely genetic investigations, other
types of studies have been conducted to estimate the
existence and degree of genetic and environmental
contributions to the etiology of certain psychiatric disorders.
Twin studies and adoption studies have been successfully
employed for this purpose.
• Twin studies examine the frequency of a disorder in
monozygotic (genetically identical) and dizygotic (fraternal; not
genetically identical) twins. Twins are called concordant when
both members suffer from the same disorder in question.
Concordance in monozygotic twins is considered stronger
evidence of genetic involvement than it is in dizygotic twins.
Disorders in which twin studies have suggested a possible
genetic link include alcoholism, schizophrenia, major
depression, bipolar disorder, anorexia nervosa, panic disorder,
and obsessive- compulsive disorder (Baker, 2004; Gill, 2004)
26. • Adoption studies allow comparisons to be made of the
influences of genetics versus environment on the development
of a psychiatric disorder, Knowles (2003) describes the
following four types of adoption studies that have been
conducted:
• The study of adopted children whose biological parent(s) had a
psychiatric disorder but whose adoptive parent(s) did not.
• The study of adopted children whose adoptive parent(s) had a
psychiatric disorder but whose biological parent(s) did not.
• The study of adoptive and biological relatives of adopted
children who developed a psychiatric disorder.
• The study of monozygotic twins reared apart by different
adoptive parents.
•
• Disorders in which adoption studies have been suggested a
possible genetic link include alcoholism, schizophrenia, major
depression, bipolar disorder, attention-deficit/ hyperactivity
disorder and antisocial personality disorder (Knowles, 2003).
27. • The search for the genes that cause mental illness has been
challenging and has stimulated scientific, political and clinical
debate (Kendler, 2005).
• An example of a genetically heterogeneous (caused by more than
one gene) disorder is the rare form of Alzheimer disease that
affects people before age 65 years. Early onset AD affects only
about 10% of cases and seems to be linked to mutations in any of
three specific genes responsible for amyloid-beta, causing excess
deposits of this substance in the brains of the persons with AD.
• Current research on the genetics of mental health and illness is
confirming the genetic transmission of mental illness but also
confronting many challenges. One challenge is the chronic nature
of many mental illnesses and the gradual increase of symptoms
and behavioural problems over time, also challenging is the length
of time required for therapeutic effects of many treatments
(Tsankova et al, 2007).
28. • The proteins surrounding DNA affect which portions of the
DNA strand are accessible for transcription. This
manipulation of DNA can affect gene activity but does not
alter the genetic code. Another complication is that
psychiatric illnesses are not caused by simple genetic
mechanisms but rather by small, cumulative effects from
multiple genes (Kendler, 2006; Baum et al,2007)
29. • The proposed uses of genetics in psychiatry include the
following:
• Developing new drugs that will target molecular regulators
of gene expression that control neuroproteins and
neuroenzymes in brain regions shown to be abnormal in a
particular psychiatric illness.
• Conducting gene therapy- the introduction of genes into
existing cells to prevent or cure disease.
• Implementing studies that use ‘candidate genes’ (cloned
human genes that are functionally related to the disease
of interest) in research procedures in the laboratory.
30. Implications for Nursing
• It is important for nurses to understand the interaction between
biological and behavioural factors in the development and
management of mental illness.
• The nurse should have clear understanding of the genetic
influences i.e. the hereditary factors that predispose individuals
to certain psychiatric disorders.
• The nurse should be in the position to answer questions from
patients and families about the genetics of mental illness and to
educate them about the accuracy and limitations of current
testing procedures (Braff and Freedman, 2008; Gottesmann et
al, 2011; Lea et al, 2011).
• The nurse can objectively share the current evidence while
reminding them that this information is often preliminary, yet
growing.