05. Neurogenetics Flashcards
What are the components of deoxyribonucleic acid?
- Nitrogen base
- Ribose sugar
- Phosphate group
How much DNA do humans share with each other?
99.9%
What are natural variations in DNA known as?
SNPs (Single nucleotide polymorphisms)
This is what makes us look different (eyes, hair, skin)
Mitosis vs Meiosis
- Mitosis: 2 identical daughter cells (diploid - 23 pairs of chromosomes)
- Meiosis: 4 non-identical daughter cells (haploid - 23 chromosomes)
Why are cells made by meiosis non-identical?
- Homologous recombination (crossing-over)
- Each cell has a different 50% of the parent cell’s genes
- Allows diversity and ∴ evolution
Genes -> Protein
Genes are transcribed and translated
(1) Amino acid sequence
(2) Alpha helices/beta pleated sheets
(3) Protein folding produces tertiary structure
(4) (optional) Protein folding produces quaternary structure
What is transcription?
In the nucleus, the gene’s DNA sequence is copied into messenger RNA (mRNA).
What is translation?
A ribosome attaches to the mRNA and moves along the mRNA, reading each triplet codon (3 bases) and using transfer RNAs (tRNA), to form the amino acid sequence
tRNA -> a complementary codon (e.g. UAG) attached to an amino acid
What are Mendel’s Laws?
- Law of Segregation - individuals have 2 versions (alleles) of each gene. Reproduction ‘segregates’ the versions, so each gamete gets only one.
- Law of Independent Assortment - every gene is inherited separately (unless they are on the same chromosome)
- Law of Dominance - some alleles are dominant and will always be expressed
Genetic disorders
What is Huntington’s Chorea?
- Dominant inheritance
- Causes neurons to break down & die
- Attacks areas of the brain that control voluntary movement
- Physical symptoms: chorea (uncontrollable movement), abnormal posture
- Mental symptoms: behaviour, emotion, thinking & personality problem
- Single gene disorder, located on chromosome 4 (Gusella et al., 1983)
Genetic disorders:
Phenylketonuria (PKU)
- Recessive inheritance
- Mutation of PAH (enzyme that breaks down dietary phenylamine) gene
- If not treated, phenylamine can reach harmful levels
- Physical symptoms: epilepsy
- Mental symptoms: learning disabilities & behavioural problems
- In the UK we do screening at birth
What is Monosomy?
- One copy of a chromosome
- Lethal to embryos
- E.g. Turner syndrome, Cri du chat syndrome
What is Trisomy?
- Three copies of a chromosome
- Often lethal to embryos, but can be survived
- E.g. Downs syndrome (location: chromosome 21)
X-linked conditions
- The X chromosome has many genes, the Y chromosome has very little
What is X-inactivation (females)
- The transcriptional silencing of one X chromosome
- The inactivated X is held in a ‘Barr body’ in the cell (Boumil & Lee, 2001)
Example of X-inactivation in cats
- in cats, colour is sex-linked.
- in tortoiseshells, the orange patches have the X with the black fur allele inactivated and held in a Barr body (and vice versa)
X-linked syndromes:
Rhett syndrome
- almost exclusively affects females (XX), because males die before birth
- 1 in 10,000
- Mutation in gene MeCP2, which turns off the expression of unwanted genes
- Inactivation means not all cells express the mutant MeCP2, so there is varying presentation
X-linked syndromes:
Fragile X
- Learning disability (most common)
- 1 in 4,000 (males)
- 1 in 6,000 (females)
- Mutation in FMR1 gene, which encodes FMR protein, which moves mRNAs between cytosol and nucleus
What is epigenetics?
- How cells control gene activity without changing DNA
- E.g. turning genes on/off
- Early experiences influence later stress/depression
Epigenetics in animals
- Maternal care (licking & grooming) influences epigenetic expression of Nr3c1 gene
- Nr3c1 encodes glucocorticoid receptor (GR)
- Absence of maternal care -> low levels of GR (for life)
- Low GR -> increased stress hormones & anxiety/depression, lower response in HPA axis
What are Transgenerational Epigenetics?
- Parents can pass on epigenetic changes (caused by environment)
- Chemicals (smoking/drinking) can modify histones in sperm cells
- Causes altered RNA in offspring (and grandchildren)
Alzheimer’s disease
- Mutations in ‘risk genes’ cause AD amyloid precursor protein (on Chromosome 21)
- Only one SNP difference between APOE3 (safe) and APOE4 (Alzheimer’s)
What is concordance?
Extent to which a trait is seen in 2 individuals
Genetics of schizophrenia
- MZ twins: 48% concordance
- DZ twins: 17% concordance
- Suggests schizophrenia highly heritable (but not entirely genetic)
