5. Neurogenetics Flashcards
Genetics is the scientific study of i____ v___: of how traits are p____ d____ through g____, and the role of g____ in determine those traits
inherited variation
passed down, generations
genes
Cells are the basic b____ b____ of all l____ things
building blocks, living
Chromosomes are found i____ your cells. A chromosome is a t____ w____ c____ of DNA
inside, tightly wound coil
DNA s____ make up genes
segments
Genes are long sequences of b____ p____ in the DNA that e____ p____
base pairs, encode proteins
Your genes are an i____ m____ for your body
instruction manual
there are approx ____ genes on human chromosomes
23,000
Each gene carries i____ that determine your f____/t____, such as eye colour, hair colour and height
instructions, features/traits
Humans have __ pairs of chromosomes and __ base pairs of DNA
23, 3 billion
DNA stands for d____ a____ and contains 3 parts:
1. N____-containing b____
2. F____-c____ s____
3. P____ group
deoxyribonucleic acid
1. Nitrogen-containing base
2. Five-carbon sugar
3. Phosphate group
Humans share over __% of our DNA sequence with each other
99.9%
Natural variations in our DNA are known as s____ n____ p____ (SNPs)
Around __ SNPs identified through human genome project sequencing.
The unique combination of SNPs that we i____ from our parents are responsible for the genetic component that makes us d____ to one another
single nucleotide polymorphisms
~ 3,300,000
inherit, different
Mitosis cell division happens in s____ cells and daughter cells are i____ to parent cell
somatic, identical
Meiosis cell devision happens in g____ and daughter cells contain h____ the number of chromosomes
gametes, half
Meiosis:
1. H____ r____ or “crossing over”
2. Allows g____ d____
3. Offspring all share __% of each parental genes, but a different __%
- Homologous recombination
- genetic diversity
- 50%, 50%
(natural selection and evolution)
A gene is expressed through the processes of t____ and t____
transcription, translation
During transcription, the enzyme, the enzyme R____ p____ uses DNA as a template to produce a p____-m____ t____. The p____-m____ is processed to form a mature m____ molecule that can be t____ to build the protein molecule (p____) encoded by the original gene
RNA polymerase
pre-mRNA transcript
pre-mRNA , mRNA
translated
polypeptide
Transcription is in the n____, the gene’s DNA sequence is c____ into m____ R____
nucleus
copied
messenger RNA (mRNA)
Translation is where a r____ attaches to the m____ and moves along the m____, reading each t____ codon (3 bases) and using t____ R____ to put together the a____ a____ chain to make a p____
ribosome
mRNA
mRNA
triplet
transfer RNAs (tRNA)
amino acid
protein
Mendel’s law (Mendelian Inheritance):
1. Gregor Mendel (1865) - inheritance through “t____ u____”
2. Height in peas - d____ trait (tall or short, no i____
3. Trait that is controlled by a s____ g____ in one or two forms (a____)
4. A____ = v____ of a gene
5. __ copies of the gene in each parent pea, __ copy is carried to each of the offspring - with tall (__) or short (__)
6. Height - Tall (__) is d____, short (__) is r____
7. When c____-f____ all the first generation (F1) offspring are t____
8. But short character reappears in the second generation (F2) in just a q____ of the offspring
- transmissible units
- dichotomous, in-between
- single gene, alleles
- Allels, variants
- 2, 1, TT, tt
- T, dominant, t, recessive
- cross-fertilised, tall
- quarter
Mendel’s law:
1. Law of s____ - each individual has two a____ of a gene, one from each parent. These a____ s____ during reproduction, so each g____ gets only one
2. Law of I____ A____ - genes for different traits are inherited i____ of each other (unless they are linked on the same chromosome)
3. Law of D____ - some alleles are d____, while others are r____
- segregation, alleles, alleles segregate, gamete
- Independent Assortment, independently
- Dominance, dominant, recessive
Genotype = g____ i____
genetic information
Phenotype = how it displays… o____ p____ traits (interaction of g____ with e____)
observable physical, genotype, environment
Alleles = v____ of g____
variants of genes
M____ in the genetic sequence can lead to d____
Mutations, disorders
Gene variations/mutations can affect f____ or e____
function (coding sequence e.g. Huntington’s)
expression (non-coding, regulatory sequences)
Huntington’s Chorea is d____ inheritance. It is an inherited disorder that causes n____ cells in parts of the brain to g____ b____ d____ and d____. The disease attacks areas of the brain that help to control v____ movements. People living with HD develop u____ dance-like movements and a____ body postures, as well as problems with b____, e____, t____ and p____
dominant, nerve (neurons), gradually break down, die, voluntary, uncontrollable, abnormal, behaviour, emotion, thinking, personality
Huntington’s Chorea is a single gene disorder on chromosome __
4
Autosomal dominant inheritance = a s____ copy will be dominant and lead to the disease
Autosomal dominant inheritance: single copy will be dominant and lead to the disease (if 1 parent has Huntington’s, 50% of the offspring will develop Huntington’s).
Phenylketonuria is r____ inheritance. It is a mutation in the PAH gene (phenylalanine hydroxlase (PAH)) - e____ that breaks down d____ p____. If PKU is not treated, p____ can build up to harmful levels in the body, causing i____ d____, b____ d____ and e____. Build up of p____ is toxic to d____ brain. PKU is s____ for at birth in the UK, as symptoms can be prevented by d____
recessive
enzyme
dietary phenylalanine
phenylalanine
intellectual disability, behavioural difficulties, epilepsy
phenylalanine, developing
screened, diet
Monosomy = s____ copy of a chromosome. E____ l____ (e.g. c____ d____ c____ syndrome)
single
embryonic lethal
cri du chat
Trisomy = t____ copies of a chromosome. Very high rate of e____ l____ (e.g. d____ syndrome)
three, embryonic lethality, downs
Downs syndrome is trisomy in chromosome 21 and leads to smaller brain size of f____ l____ and c____, mild to moderate i____ a____ and high risk of early onset A____ d____. Symptoms narrowed down to __-__ genes on chromosome 21
frontal lobe, cerebellum
intellectual ability
Alzheimer’s Disease
20-40
The wrong number of chromosomes impacts normal development reflecting importance of g____ d____
gene dosage
Y chromosome has very few genes mostly governing male s____ f____. X chromosome has many genes that play v____ role in both s____
sexual function
vital, sexes
X i____ in females switches off one copy of X chromosome during e____
inactivation, embryogenesis
X-linked disorders vary in their p____ according to s____
penetrance, sex
X-i____ ensures that the d____ of a____ genes is maintained in all individuals
inactivation, dosage, active
Female mammals t____ s____ one of their two Xs in a complex and highly c____ manner (Lyon, 1961). The inactivated X chromosome then c____ into a compact structure called a B____ b____, and it is stably maintained in a s____ state (Boumil & Lee, 2001)
transcriptionally silence, coordinated
condenses, Barr body, silent
An adult female is a mosaic of c____ derived from different e____ cells. Within a clone, all the cells inactivate the s____ X, but between clones the choice is random. If she happens to be a c____ of an X-linked r____ disease, this can have major implications
clones, embryonic, same, carrier, recessive
Huntington’s Disease:
35 or more C__ repeats on a mutated H____ gene on chromosome __ leads to n____ d____ which leads to a____ of b____ g____ and e____ of l____ v____
CAG, HTT, 4, neuron degeneration, atrophy, basal ganglia, enlargement, lateral ventricles
Rett syndrome:
1. Progressive n____ disorder almost e____ affecting f____, leading to profound d____
2. Rare condition - 1 in __
3. Mutation in the gene M____ - this “t____ r____” turns off the e____ of unwanted genes during s____ f____
4. X-l____
5. S____ mutation rather than i____
6. X-i____ means that not all cells will express mutated M____ gene, therefore v____ p____, sometimes see m____ symptoms
7. Affected males do not have a “g____ c____” of M____ - much more severe p____, e____ l____ or die soon after b____
- neurodevelopment, exclusively, females, disabilities
- 10,000
- MeCP2 (methyl CpG binding protein 2), “transcriptional repressor”, expression, synapse formation
- X-linked (gene on the X chromosome)
- Spontaneous, inherited
- inactivation, MeCP2, variable penetrance, milder
- “good copy”, MeCP2, phenotype, embryonic lethal, birth
Fragile X (X-linked):
1. Most common i____ form of l____ d____
2. Relatively c____
3. X-linked - symptoms predominantly in m____
4. Mutation in 5__ end of the F____ gene, consisting of an a____ of a C____ repeat
5. The F____ gene encodes the F____ protein, which is thought to shuttle select m____ between c____ and n____
6. Milder penetrance in f____ due to X-i____, so not always recognised
- inherited, learning disability
- Common (1 in 4000 males; 1 in 6000 females
(carrier of ‘premutation’: 1 in 259 females; 1 in 800 males)) - males
- 5’UTR, FMR1gene (fragile X messenger ribonucleoprotein 1), consisting of an amplification of a CGG repeat (200+ copies; normally between 6 and 40 repeats).
- FMR1, FMR, mRNAs, cytosol, nucleus
- females, inactivation
Epigenetics is the study of how cells c____ g____ a____ without changing the DNA sequence. Epigenetic changes are m____ to DNA that regulate whether genes are turned o____ or o____. These modifications are attached to DNA and do not change the s____ of DNA building blocks
control gene activity, modifications, on, off, sequence
Epigenetic mechanisms are affected by:
1. D____ (in u____ and c____)
2. Environmental c____
3. D____/p____
4. A____
5. D____
- Development (in utero, childhood)
- chemicals
- Drugs/pharmaceuticals
- Aging
- Diet
DNA methylation - Methyl groups can t____ DNA and a____ or r____ genes
tag, activate, repress
Histones are proteins around which DNA can w____ for c____ and gene r____
wind, compaction, regulation
Histone modification - the binding of epigenetic factors to h____ “t____” alters the extent to which DNA is w____ around h____ and the a____ of genes in the DNA to be a____
histone “tails”, wrapped, histones, availability, activated
Epigenetic modifications can be s____ through the life course, but some are affected by the e____.
There is early development influence on s____ r____ and d____ in later life.
Studies found an effect of m____ care in mice on the e____ r____ of the expression of Nr3c1, the gene that encodes the g____ r____.
Absence of licking lead to promoted m____ and low levels of G____ r____
M____ retained through lifetime. Without G____ r____, there was loss of f____ in HPA axis, increased s____ hormones and increased a____/d____
stable, environment
stress resilience, depression
maternal (specifically of licking and grooming pups), epigenetic regulation, glucocorticoid receptor (GR)
methylation, glucocorticoid receptors
Methylation, GR, feedback, stress, anxiety/depression
E____ influence on p____ can affect o____.
Disrupted histones in s____ cells:
Showed altered R____ profile in o____ (and g____-o____)
Histones can be modified by c____ (e.g. smoking, drinking)
Environmental, parents, offspring
sperm
RNA, offspring, grand-offspring
chemicals
The unique combination of Single Nucleotide Polymorphisms (SNPs) we inherit from our parents are responsible for the g____ c____ that makes us d____ to one another
genetic component, different
Gene association studies:
1. GAS look for sorting of SNPs in c____ genes
2. Genome wide association studies (GWAS) look for what SNPs sort with d____ state
- candidate
- disease
Mutations in PSEN1, PSEN2 and a____ p____ p____ (APP) cause Alzheimer’s disease. They are all on chromosome __ (D____ t____)
amyloid, precursor protein, 21, Down’s trisomy
Alzheimer’s disease is associated with the build up of a____ b____ p____ in the b____
amyloid beta plaques, brain
Risk of AD has been associated with SNP difference in APOE_ (c____ a____) and APOE_ (changes an a____ a____ in protein)
APOE3 (common allele)
APOE4 (amino acid)
Concordance = the degree to which a trait is seen in __ individuals.
Concordance rates in twins show that Huntington’s disease is p____ g____ whereas Schizophrenia and bipolar disorder and p____ and e____
purely genetic
polygenetic and environmental
In a study of genetics of schizophrenia, it was found that there was a __% concordance rate in MZ twins and a __% concordance rate in DZ twins. This shows there is a large g____ c____, but not p____ g____
48%, 17%, genetic component, purely genetic
In a GWAS of over 150k people (36,000 with schizophrenia), they found __ schizophrenia-associated genetic loci. These genes included ones associated with s____ t____, g____ and d____
108
synaptic transmission, glutamate and dopamine (Dopamine D2 receptor)
Advantages of animal studies include:
1. S____ of genes and biological f____ with humans
2. C____ of behaviour with humans
3. Create i____ strains of animals that are g____ i____
4. Control e____ conditions
5. M____ genes: m____ or r____ particular gene, or i____ copy of a human gene
- Similarity, function
- Conservation
- inbreed, genetically identical
- environmental
- Manipulate, mutate, remove, insert
Advantages of genetic studies of mice:
1. C____-effective culturing and handling
2. Can easily be b____ in the lab
3. Short l____ c____
4. Genetic t____ and well u____ genetics
5. Similarity to human biology and d____ m____
6. Amenable to e____ m____
- Cost
- bred
- life cycle
- tractability, understood
- disease manifestation
- experimental manipulation
Synteny between human and mouse chromosomes:
1. Human chromosome 1 - mouse chromosomes __ and __ respectively, with a small bit on chromosome __
2. The long arm of chr 21, which includes d____ s____ c____ r____, occurs intact on mouse chromosome __
3. The X and Y chromosomes of the two species are almost entirely h____
- 1, 4, 8
- downs syndrome critical region, 16 (mice can therefore serve as a useful animal genetic model of Down Syndrome.)
- homologous (as expected because the basic sex-determining genetic mechanisms is shared by all mammals)
I____ strains of mice will have different genetics, neurobiology and behaviour. Comparison of these strains can tell us about how g____ influence b____
Inbred, genetics, behaviour
Three genetically engineered mouse models:
1. K____ - functionally d____ a gene
2. K____ - introduce a s____ m____
3. T____ - multiple copies of e____ DNA
- Knockout, delete
- Knockin, specific mutation
- Transgenic, exogenous
