Human genetic in psy Flashcards
Phenotype
•Observable properties of an organism produced by the genotype and environmental influences
Down syndrome phenotype
–Sloping forehead –Protruding tongue –Short stubby limbs –Slightly flattened nose –Almond-shaped eyes –May have congenital eye, ear and heart defects
Chromosomes
•Most of our cells contain 46 chromosomes
•The 46 chromosomes are actually 23 pairs
–1 set from mother, 1 set from father
–except gametes: each contain only 23 chromosomes
–Gametes are the sex cells - sperm from male and ova from female
•Each chromosome pair carries genes of the same type
•These chromosome pairs match in size and the functions they serve
Karyotype
- The karyotype is a description of the chromosomal content of a cell
- The autosomes (non-sex chromosomes) are numbered 1 to 22
- The sex chromosomes are either X or Y
Variations in karyotype
47, X Y + 21 Down (cause mild to severe intellectual disability and physical abnormality) treat by surgery, specila intervention and education program. at 20, 1/1900, at 35 1/300 at 45 1/30
47, X X + 21 Down
47, X X Y Klinfer Extra X chromosome cause physical abnormality, treat by hormone therapy. one in 600
45, X Turner cause severe hormonal and intellectual issue, hormone therapy, 1/2500 female
47, X Y Y sydrome above averageheight, no treatment, 1/1000
Klinefelter syndrome
•XXY condition can affect development in 3 ways:
–Physical development: weak muscles and reduced strength. Lagging in physical development.
–Language development: Between 25 and 85% of XXY males have some language difficulties
–Social development: XXY males tend to be quieter and undemanding compared with XY males
Chromosomes role
- A chromosome carries the genetic information of the body
- Information is arranged in a linear sequence
- Chromosomes are made up of chromatin. Chromatin constitutes nucleic acids (DNA and RNA) and proteins (histones and non-histones)
- Chromosomes are only visible during cell division processes, called mitosis and meiosis. Otherwise, they unfold and uncoil into a diffuse network within the nucleus
Deoxyribonucleic acid
DNA
- Primary structure (sequence) of DNA is described by the order of the bases in a 5’ to 3’ direction
- Humans have ~ 3.3 x 109 bases
- The locus is used to describe a sequence of DNA situated on a specific region on a chromosome
- DNA is a double-stranded structure consisting of 2 nucleotides held together by hydrogen bonds between the bases in opposing strands
- DNA molecules are organized into stretches of sequence called genes
Genes
•Each gene has one or more specific effects upon the phenotype of the
organism.
•A gene can recombine with another gene
•A gene can mutate into different forms
•Genes are expressed at different time points in life
•A gene can only influence development when it is turned on and is
expressed
•For the DNA to impart information, it must first be transcribed
Transcription and
Translation
- The strand of DNA acts as a template for the synthesis of ribonucleic acid (RNA)
- Like DNA, RNA forms stable structures by base-pairing
- DNA information can be copied to RNA for transcription and translation and carried to other areas of the cell to create proteins
- Messenger RNA carries the instructions specifying sequences of amino acids
- Groups of three bases of mRNA serially code for each amino acid
- These groups of 3 bases are called codons
- There are potentially 64 possible codons, but in nature there are only 20 different amino acids
Areas of DNA
ORF: open reading frame
UTR: un-translated region
RBS: ribosome binding site
Promoter: region of DNA that initiates transcription of the gene
Operon: is a functioning unit of genomic DNA containing a cluster of genes under the control of a single promoter
Polycistronic: codes for more than one protein
Proteins`
•20 different amino acids •Proteins are the end product of gene expression •Protein types: –Enzymes –Haemoglobin –Insulin –Collagen –Keratin –Histones –Actin and myosin –Immunoglobulins
Alleles
- About one-third of human genes have two or more different forms, called alleles
- An allele is one of two or more forms (or variations) of a gene
- The alleles of a given gene influence the same trait or characteristic
- E.g. eye colour
- The different allele forms result in different eye colours (green, brown, hazel, grey etc)
Gene Expression
- The dominant allele is the form of the gene that is expressed if present.
- The recessive allele is expressed if a dominant allele is absent.
Polygenic Inheritance
•When traits are governed by more than one
gene
•Applies to most traits and behaviors of interest
to behavioral scientists
Mutations
•Mutation is the process of change in the sequence of DNA
•Mutations are the source of genetic variation and the basis for natural selection
•Mutations have a wide range of effects on organisms, depending on the type and location of mutation
•They can occur spontaneously or be induced by external factors such as exposure to chemicals and radiation
•There are four main types of mutations
–Base substitutions
–Deletions of DNA
–Insertions of DNA
–Whole or partial chromosomal abnormalities
Genetic origins of disease
•Over 5,000 human diseases and disorders are mpresently known to have genetic origins
Recessive gene: PKU, sickle-cell anemia, Tay-Sachs mdisease, cystic fibrosis
Single dominant gene: Huntington’s disease, neurofibromatosis
Polygenic inheritance: cancer, heart disease, asthma, mpsychiatric disorders, behavior disorders
Sex-Linked inheritance: red-green color blindness, hemophilia, Duchenne muscular dystrophy, fragile-X syndrome
Chromosomal anomalies: Down syndrome (trisomy 21), Klinefelter syndrome (XXY), Turner syndrome (XO)
Regulator gene defects: genetic male with female genitalia
Tay-Sachs disease
- A fatal, autosomal recessive neurodegenerative disease of infancy and early childhood
- Rare in most populations
- Caused by mutations of HEXA gene on chromosome 15q23-q24.
- First identified in 1969
Tay-Sachs disease vunerable pop
•Population studies and pedigree analyses suggest that mutations may have arisen from small founder populations:
–Carrier frequency is 1:25 in Ashkenazi Jews
–Same mutation is found in Cajun population in southern Louisiana
–Two different mutations are common in French Canadians
–Higher carrier frequency in Irish-American and Pennsylvania Dutch communities compared with general population
•Incidence in unscreened Jewish populations is 1 in 3,900 births
•Internationally, screening has reduced the incidence of Ashkenazi Jews with TSD-affected children by more than 90%
Tay-Sachs disease education in australia
•Australian high-school-based preconception genetic screening programs help young people through screening and education
–Choosing a partner not at risk
–IVF, donor gametes, adoption
–Selective terminations
–Child-free
•Aim is to optimize reproductive and life choices for participants.
Huntington’s disease
- Progressive neurodegenerative disorder
- Autosomal dominant
- Huntington gene isolated in 1993, on chromosome 4 at 4p16.3
- > 40 repeats of CAG (cytosine, adenine, guanine) trinucleotide in coding region of gene
- Mean onset ~40 yrs, death 12-15 years afterwards
- Prevalence 5-10 per 100,000 people
- Symptoms include cognitive deterioration, personality change, memory loss and depression, and choreic and slow movement
- The gene contains an expanded trinucleotide repeat (CAG) that ranges from 9-35 in healthy adults, and from 36 to 180 in Huntington’s disease.
- Alleles with 36-39 repeats show “reduced penetrance”- only some individuals will go on to develop clinical symptoms.
- Individuals with juvenile-onset (Westphal variant) usually have expansions >55 repeats and develop Huntington’s disease before 20 years.
- Onset appears to be earlier when the transmission is from the father.
Chorea and bradykinesia
characterise movement
control in HD
Voluntary
• Bradykinetic
• Inconsistent and inefficient movement
-Abnormal co-contractions of muscles
-Prolonged EMG bursts
-Less efficient and more variable movements in handwriting
• Sequential and simultaneous movement difficulties
Involuntary
• Involuntary ‘dance-like’ choreic movement
• Abates in advance stages of disease, when akinetic and mbradykinetic movements become mclearer
Broad sub-cortical and cortical damage in HD
- Neuronal and astrocyte loss in the basal ganglia (caudate, putamen, global pallidus and other areas)
- Selective degeneration of GABAergic neurons of striatum
- As disease progresses, greater cortical atrophy occurs
Schizophrenia
•Fundamental and characteristic distortions of thinking, perception and affect that are inappropriate or blunted
•Psychopathological thoughts
–Hallucinations, paranoid or bizarre delusions, and disorganised speech and thinking leading to significant social and occupational dysfunction
•Onset typically occurs in young adulthood
•Affects ~ 0.5% of population
•Course of schizophrenic disorders can be continuous or episodic
•Not due to depression or manic symptoms unless it is clear that schizophrenic symptoms antedate the affective disturbance; not due to drug intoxication or withdrawal
Genetic risk of Schizophrenia
•Genetic risk for schizophrenia is more likely to be continuous
than categorical.
•The last 5 years of genetic research has produced evidence
that genetic risk for schizophrenia is largely polygenic.
Fragile-X syndrome
- FXS is the most common inherited form of intellectual disability
- Expansion mutation of a CGG repeat sequence in the FMR1 gene at the locus Xq27.3
- Leads to silencing of the gene and absence of the gene product - the FMR1 protein product
- This protein is essential for synaptic plasticity, development of the shape of the brain, and cognitive development
- Boys are typically more severely affected than girls
Phenylketonuria
- Children with phenylketonuria (PKU) are unable to metabolize phenylalanine.
- Phenylalanine is an amino acid found in high-protein foods (e.g., meats, eggs, fish, nuts) and in some artificial foods (e.g., diet drinks, artificial sweeteners).
- PKU is a disorder that is related to a defective gene on chromosome 12, in which the body cannot break down this amino acid. It builds up in the body and can cause problems with brain development.
- With early diagnosis and a properly restricted (phenylalanine-free) diet, however, mental retardation resulting from PKU can be avoided.
How gene regulation affect development
- Normal human development will only occur if a given gene is turned on and off at the correct time, in the right place and for the right length of time
- Some genes are only turned on in a few cells and for only a few hours and then are switched off permanently (e.g., during development of the embryo)
- Other genes are involved in the basic functioning of almost all cells almost all of the time
- Regulator genes control the switching on and off of genes
- External factors can affect the switching on and off of genes;
- There is a continuous interaction between the environment and the genotype;
- The range of reaction refers to all the phenotypes that could theoretically result from a given genotype, given all the environments in which it could survive and develop…
Phenotype and Genotype of children
•A child with a given genotype would likely develop quite differently in a loving, supportive family compared with growing up in an alienated, abusive family.
•The child actively creates and explores the environment in which they live.
•By virtue of their nature, they evoke different responses from
others.
•Children actively seek out things that they inherently enjoy.
•This increases as they age – so children at school will become friends with people who have similar energy levels and interests.
Epigenetics
•Heritable (but reversible) changes in gene expression that are not coded in the DNA sequence but by post-translational modifications in DNA, histone proteins and in microRNA
•Environment can produce persistent alterations in the phenotype through altering gene expression
•There are three different mechanisms involved in the regulation of genes
–Histone modification
–DNA methylation
–microRNA
Autoimmune disorders
Autoimmune diseases encompass more than 80 disorders, affecting ~7% of population
–E.g., Rheumatoid arthritis, Lupus, Type 1 diabetes, Multiple sclerosis
•Monozygotic twin studies often show discordance of these diseases, suggesting a role for environmental factors contributing to disease development
•Interplay between genetic and environmental factors may predispose and progress autoimmune diseases
–E.g., Exposure to UV radiation, infections, tobacco smoke, pollutants,
alcohol consumption
–Gender bias (females), age, latitude of country point towards environmental factors contributing to disease predisposition
•Circulating immune cells are in constant exposure to environmental factors
•Currently, the precise epigenetic mechanisms involved in autoimmune disorders is unclear
Genetics and environment
- The interplay between genes and experience is very complex
* This model of hereditary and environmental influences can help to simplify this interplay
Phylogenetic continuity
- We are just another type of animal.
- Due to our shared evolutionary history, we share many characteristics and developmental processes with other living things.
- The size of human brain is markedly larger and more complex than other mammals
- Principles of cortical development and physiology are shared
Cell reproduction: Meiosis
- Cell reproduction: Meiosis
- Meiosis is a special type of cell division, necessary for sexual reproduction.
- Meiosis produces gametes
- The DNA is replicated, recombined, and the cell divides twice
Sperm
• Ejaculation – 500 million sperm
• Sperm physiology
• Sperm’s travel ~ 6 hours (6-7 inches) vagina,
uterus, fallopian tube
• Only about 200 ever get close to the ovum
Why does the amount of sperm aarrive at the tube isl ow
– Tangles
– Wrong fallopian tube
– Abnormal shapes
Three phases of prenatal
development
• Period of the zygote
– 0 to 14 days
– From conception to implantation into the wall of the uterus
• Period of the embryo
– 3 to 8 weeks
– Virtually all the major organs are formed
• Period of the fetus
– 9th week until birth
– All the major organs begin to function and the developing organism grows
The zygote
- sperm Penetration
- Sealing of the membrane
- Tail of sperm falls off, contents of head gush into ovum
- Within hours the nuclei of the two gametes merge, producing the zygote
- Within 12 hours of fertilisation, the zygote splits into two equal parts, each containing a full set of genetic material. This process is called…..mitosis
Cell reproduction: Mitosis
- Mitosis is a process of cell replication and division, in which the cell separates the chromosomes in the cell nucleus into two identical sets, in two separate nuclei
- These two daughter cells are genetically identical to each other and their parent cell
Blastocyst
Ball-like structure that contains 60-80 cells, within 4 days of conception
• Implantation occurs between 8 and 14 days from conception
• Rates of success
– Only half of all fertilised ova are firmly implanted
– Perhaps as many as half of all such implants are genetically abnormal or fail to develop, or burrow into a site incapable of sustaining them
– ¾ of zygotes fail to survive this initial phase of development
Embryo
- Cell differentiation
* The inner cell mass will become the embryo and the rest of the cells will become the amniotic sac and placenta
