Genetics and Brain Development Flashcards
Spinal bifida
Neural tube disorder that causes the bottom of the spinal cord to not close
Embryonic brain regions of the hindbrain
Mesencephalon and myelencephalon
Where does myelination start and where does it lead to?
Occurs in the rostral direction starting with the spinal cord, then hindbrain, midbrain, and forebrain
What does blue light do in optogenetics?
Activates on opsin called channelrhodopsin to allow positive ions in the neuron for firing of the neuron
Examples of sex-linked characteristics?
Hemophilia and color blindness
Characteristics of the candidate gene approach
hypothesis driven, confirmatory, systematic scanning
What is neurogenesis?
Formation of neurons and glia from stem cells
How many mutations are in the average new born?
Around 130 new mutations with most having little to no effect
How are genes arranged?
Linearly on chromosomes
Genetic disorders
Fragile-X syndrome, phenylketonuria (PKU), down syndrome
When does plasticity occur?
Growth and development, learning: long term potentiation and enriched environments, following injury (limited), and possibly adult neurogenesis
What happens with synapses in people with schizophrenia and Alzheimer’s?
Too few synapses in schizophrenia and normal in Alzheimer’s until older age when there are far too few
What is cell migration?
Cells in the cerebral cortex arrive in an inside-out fashion
What does retroviral gene therapy do?
A virus enters a host cell and the virus inserts its DNA into the host’s DNA. The cell makes virus genes and proteins as it reads its own DNA.
How many genes are in the human genome?
about 23,000
What happens during differentiation in the dorsal-ventral axis?
Neurons are distinguished between sensory and motor
Where are progenitor cells found?
The ventricular zone lining the neural tube
What is a genotype?
A person’s 23 pairs of chromosomes
Example of a CNV
Huntington’s disease. Too many copies of a gene, specifically too many CAG repeats.
Abnormalities in synaptogenesis and neurocognitive disorders
Schizophrenia has less connections. Autism has a lot of immature spines
How do growth cones form synapses?
Growth cones approach muscle fibers, they make contact, and synaptic vesicles accumulate in axon terminal and synaptic receptors cluster at point of contact
What has to be taken into account when assessing heritability?
Environment
What does a heritability value of 0 represent?
Genes play no role in phenotypical differences. Ex - environmental toxin exposure
What is plasticity?
They nervous systems ability to change
How many pairs of autosomes?
22
What is histone modification?
Epigenetics. DNA may unwrap or be stopped from unwrapping from the histone
What is a gene?
Segment of DNA that produces a single protein
What are alleles?
Different versions of a gene
What is the mesoderm?
Middle germ layer that becomes connective tissue such as ligaments, muscles, blood vessels, and urogenital system
Down syndrome
Genetic disorder caused by extra chromosome
When is the peak amount of synapses in the visual cortex?
Around 5 months. Toys are brightly colored at this age
What kinds of things happen during synaptic pruning?
Late connections are killed, less efficient connections are killed, and even some neurons are killed through apoptosis
What does inside-out migration mean when speaking about neural migration?
Layer 6 develops first, then 5, etc. Layer 6 is the deepest and layer 1 is closest to the skull
What does a heritability value of 100 represent?
Genetics are completely responsible for phenotypical differences. Ex - Huntington’s disease. If you have the gene, you have the disease
What are examples of a SNP?
Cilantro. 10% of population thinks it tastes like soap. Mutation in smell.
ApoE4. 2 copies of it have a 90% chance of Alzheimer’s. Both amino acids are arginine
What types of studies are used in heritability?
Twin and adoption studies. Minnesota study of twin reared apart
What is activity dependence?
The more it is active, the more it used. Use it or lose it
Gene x environment interaction with BPA and the agouti phenotype
Rats with a high BPA diet expressed the agouti phenotype. They were much larger and lightly colored
Embryonic brain region of the midbrain
Mesencephalon
Genetic modification approaches
Knock in or transgenic models, knock out deletion, optogenetics, CRISPR-CAS9 gene editing, retroviral gene therapy
What type of unplanned genetic diversity is sickle cell anemia?
Mutation
How are genes expressed?
Transcription to translation to amino acids combining to form completed proteins
What are dizygotic twins?
Fraternal
How does histone modification work?
A methyl group (CH3) or other molecules bind to the tails of histones, either blocking them from opening or allowing the to open for transcription
Example of a critical period
Learning a language
How does optogenetics work?
Insert specific channels from algae. Light opens and closes these channels.
How is epigenetics involved in mRNA modification?
mRNA translation may be blocked or enabled. ncRNA binds to mRNA preventing translation
What is concordance?
A match, or agreement, of a trait. Both twins have it
When is the prefrontal cortex completely myelinated?
Early adulthood around 21-25
Brain structures of the telencephalon
Cerebrum (includes cerebral cortex, white matter, basal nuclei)
What does heritability refer to?
A population, not an individual
Where are most human trait values of heritability?
30%-60%
Environmental toxins causing disorders of brain development
Fetal alcohol syndrome and prenatal exposure to other drugs
What studies are used to study behavioral genetics through family linkage?
Family studies, twin studies, adoption studies, and sibling studies
When does myelination occur?
23 gestational weeks. Burst around birth. It occurs in bursts and is less gradual than most processes
What does synaptic pruning do?
Reduces the number of functional synapses. Efficiency process that focuses on the connections that matter
How does neurogenesis happen?
Progenitor cells divide by mitosis. They can become a lot of different things
Where does neurogenesis originate from?
Cells in the ventricular zone
What might relate to critical periods?
Myelin bursts and neurotrophins available in large or small amounts
What happens in apoptosis?
Cells dies through programmed cell death
What influenced synaptic pruning?
Neurotrophins and functionality of the synapse
What do genome wide association studies do?
Look at patient DNA and non-patient DNA to compare differences to discover SNPs associated with diseases
Example of higher heritability
Schizophrenia
What does synaptic density reach adult levels?
18 years
What are filopodia?
Long, fingerlike extensions from growth cones of neurities. They detect chemicals from other cells
How does the body know which parts are part of which segment during differentiation?
Hox genes
What is an example of what SNPs can do?
SNPs in the APOE gene can predict risk for Alzheimers disease
Where are the motor neurons in the spinal cord?
Ventral half. Ventral root in spinal cord.
Examples of planned genetic diversity
Crossing-over, meiosis, sexual reproduction
Where are the sensory neurons in the spinal cord?
Dorsal half. Dorsal root in the spinal cord
What is a phenotype?
Observable characteristics
What is the control referred to in knock-in and knock-out studies?
wild type
How does epigenetics explain differences in identical twin DNA?
As they get older, the twins will act different from each other but still have the same DNA
What is the ectoderm?
Outer germ layer that becomes skin and neural tissue
What happens during differentiation in the rostral-caudal axis?
The parts of the nervous system are segmented. Spinal cord, myelencephalon, mesencephalon, diencephalon, and telencephalon
Six stages of neural development
- ) neurogenesis
- ) migration
- ) differentiation
- ) circuit formation
- ) neuron death (apoptosis)
- ) pruning and rearrangement of connections
Examples of unplanned genetic diversity
Mutations, sing nucleotide polymorphisms (SNPs), copy-number variations (CNVs)
What are single-nucleotide polymorphisms (SNPs)?
DNA sequence change at one nucleotide
What do progenitor cells do?
Neurogenesis through mitosis. Neural or glial
Changes in gene expression or phenotype that don’t involve changes to the DNA sequence. Changes how DNA is used based on experience
Epigenetics
What happens during puberty?
A period of cortical thickening followed by thinning
Where was adult neurogenesis first discovered?
In rodent hippocampus and olfactory bulbs
Brain structures of the diencephalon
Thalamus, hypothalamus, epithalamus
What are axons?
Coding sequences
What is the human genome?
set of instructions for constructing a human being
When is the brain fully mature and when does it start to decrease in weight?
25 and 45
Are sex-linked characteristics more common in males or females?
Males
Which genotype is riskiest when contributing to the serotonin transporter gene?
The short/short genotype bc it is the gene and the environment playing a role in emotional problems related to stressful life events
What happens during neuronal maturation and circuit formation?
Growth cones move out to form neural connections
What are copy-number variations (CNVs)?
Variable numbers of genes or gene series
When does the highest number of synapses occur?
Childhood
Wide spread vs specific mutations
Depends on how many genes are impacted
The three stages of prenatal development
Zygote to embryo to fetus
What are critical periods?
Time when particular experience is influential and after which experience has little or no effect
How do genetic mutations occur?
Can occur spontaneously or in response to radiation, chemicals, or other mutagens
What is discordance?
A non-match, or disagreement, of a trait. One twin has it and the other doesn’t.
What does a heritability value of X=X% represent?
X% of the population variation we see in a trait can be accounted for by genetic differences.
How many pairs of sex chromosomes?
1
What is heritability?
The contribution of genetics to the variation of a trait observed in a population
What are monozygotic twins?
Identical
What is PKU?
Phenylketonuria. Genetic disorder that causes an inability to process the amino acid phenylalanine
When is the peak amount of synapses in the prefrontal cortex?
Around ages 1-5. Elementary school and learning how to raise hand, ask to go to the bathroom, etc.
Where do neurons move from and where do they move to in neural migration?
Move from ventricular zone of fetal tube to their final location. They start in the center and move out. They move with the help of radial glia
Why do teens often feel like everything is against them?
Their amygdala is developing
What are the two ways epigenetics work?
Blocks gene to stop transcription, expression.
Unlocks gene to allow transcription, expression.
What proteins are associated with motor neurons?
Sonic hedgehog protein
What does CRISPR-CAS9 gene editing do?
Guide RNA carries a guide sequence of DNA to a cell along with the Cas9 protein. The guide RNA attaches the DNA strand with it to the target DNA and the Cas9 protein cuts the guide RNA out and they leave. The DNA is swapped into the place of the old DNA and the resulting DNA is edited
How is the neural tube closed?
Neural plate to neural groove to the neural tube. Neural plate on ectoderm that folds in creating the neural groove that digs in the mesoderm and closes off to form the neural tube inside the mesoderm below the ectoderm.
Stages of apoptosis
Cell death genes to activate caspases to breakup DNA and proteins to cell death
What does transcription do?
DNA partially unwinds and a strand of complementary RNA is made. It makes RNA
What does translation do?
RNA instructs ribosomes to produce amino acids. RNA to amino acids
Why do teens exhibit risky behavior?
Immature connections between the limbic system, prefrontal cortex, and amygdala
What does yellow light do in optogenetics?
Activates off opsin called halorhodopsin to allow negatively charged ions in the neuron to stop the neuron from firing
Signs of early differentiation in prenatal development
Germ layers, neural plate, neural groove, neural tube, prosencephalon, mesencephalon, and rhombencephalon
How many cells are made a minute in neurogenesis?
Up to 250,000
Dominant, codominant, and and recessive alleles
Dominant - always expressed
Codominant - expressed sometimes
Recessive - both expressed
What proteins are associated with sensory neurons?
BMP protein
Homozygous vs heterozygous alleles
Homozygous - copies are the same
Heterozygous - copies are different
Microcephaly and anencephaly
Neural tube defect that causes part of or all of the cortex to not develop
What is the endoderm?
Inner germ layer that becomes many internal organs
Brain structures of the mesencephalon
Midbrain (part of the brainstem)
When is the peak number of synapses in the brain?
It is different for different areas of the brain
What happens during synaptic rearrangement?
Synapses are rearranged from a diffuse pattern to a more focused pattern
What are sex-linked characteristics?
Recessive genes on one X chromosome that are not duplicated on the Y chromosome will be expressed in male offspring
Characteristics of genome wide association study
Data-drive, exploratory, relies on mutation map
Gene x environment interaction with the serotonin transporter gene, stress, and depression
Does not show complete dominance, two alleles (short and long), emotional problems in response to stressful life events or frequent bullying
What happens with synapses in people with autism?
They have too many synapses
The three germ layers and what will they become?
Ectoderm, mesoderm, and endoderm. They will grow into something else
How does cell migration occur?
Cells are guided by radial glia
Negative effects of sickle cell
Poor oxygen capacity. Bad on mountain top
How is epigenetics involved in DNA modification?
Transcription of DNA in mRNA may be enabled or blocked. It is blocked by methyl groups binding to CG base pairs to block transcription
Embryonic brain regions of the forebrain
Telencephalon and diencephalon
How are positive, neutral, and negative effects of mutations determined?
Depends on content of the environment
What do mice in complex environments show in their neurons?
More branches and spines
What are CNVs associated with?
Huntington’s disease and Down syndrome
Example of lower heritability
Anxiety
What are lamellipodia?
Flat, sheet like extensions from core of growth cones
When is concordance used?
Twin studies
Brain structures of the myelencephalon
Medulla oblongata (part of the brainstem)
Why do teens need more sleep than older adults?
Higher myelination levels lead to increased need for sleep
Positive effects of sickle cell
Protection against malaria. Good in jungles
What do decreased levels of dopamine and serotonin lead to?
Mood swings, sensation seeking, and emotional regulation problems
What is fasiculation?
When neurons bundle to follow the same path. They like to do this
Increased amounts of what can affect the limbic system?
Estrogen and testosterone
What are mutations?
Errors in DNA replication
Brain structures of the mesencephalon
Pons (part of the brainstem) and cerebellum
What do amino acids do in gene expression?
Combine to form completed proteins
What are neurotrophins?
Help neurons to grow and thrive
How does fetal alcohol syndrome occur?
Binge drinking in the second and third trimester
What are the two parts of a growth cone?
Filopodia and lamellipodia
What type of process is epigenetic?
Dynamic. It is constantly changing and happening
Imprinted allele
Genes are expressed in a parent of origin manner
What does the knock-out approach do?
Take genetic info and cut it out to see what happens
What are introns?
Noncoding sequence found between axons (regulatory genes). Not tied to protein but often regulatory
Brain changes related to healthy aging
Medial temporal lobe areas involved with memory and executive pathways connecting basal ganglia and frontal lobes
What do growth cones do?
They test which way the neuron should expand
What roles might neurogenesis play?
Adult learning and memory, cognitive decline in decline of neurogenesis, multiple reserves help resist loss of function
What does the knock-in approach do?
Take genetic info from other species and add it to a different species. Humanizing a mouse
How do neurotrophins impact apoptosis?
Cells compete for a finite amount of resources and if they can’t get enough neruotrophins, they die due to enzymes
How many nucleotides in the haploid and diploid human genome?
3 billion haploid and 6 billion diploid
What is epigenetics?
Heritable changes in gene activity and expression
