Neurogenetics Flashcards
describe the DNA structure function.
- double helix structure made from two chains of phosphate and deoxyribose.
- four nucleotide bases - adenine, thymine, cytosine, guanine
what is natural variations in human genetics known as?
single nucleotide polymorphisms.
what is the difference between mitosis and meiosis?
mitosis involves somatic cells where daughter cells are identical to parent, whereas meiosis involves gametes where daughter cells contain half the number of chromosomes.
defne genes.
long sequences of base pairs in the DNA that encode proteins.
what are genes turned on by?
transcription factors, which are activated during development or intra signalling cascades.
define transcription.
in the nucleus, the genes DNA sequence is copied into messenger RNA (mRNA).
mRNA is translated to form proteins, define translation.
a ribosome attaches to the mRNA and moves along the mRNA, reading each triplet codon and using transfer RNAs to put together the amino acid chain to make a protein.
describe mendel’s law.
peas:
- inherited properties in pea plants - tall V short
- height - dichotomous trait (tall or short)
- trait is controlled by a single gene
in mendel’s law, when cross fertilised, F1 offspring are (tall/short).
tall
in mendel’s law the short character reappears in the in F2, what is the ratio to tall and short.
3 tall : 1 short (one quarter are short in offspring)
which out of tall and short is dominant?
tall is dominant, short is recessive.
homozygous means…
identical genes
heterozygous means…
non-idneitical genes
what is the difference between genotype and phenotype?
genotype refers to genetic information, whereas phenotype refers to how it is displayed.
define alleles.
variants of a gene.
what do single gene disorders involve?
- dominant
- recessive
what do gene variations and mutations affect?
function (coding sequence) and expression (regulatory sequences).
describe Huntington’s disease.
- dominant inheritance.
- onset age: 35-55 years.
- degeneration of movement, temperament and cognition.
- if one parent has Huntington’s, 50% the offspring will.
what chromosome does Huntington’s effect?
chromosome 4, due to excessive repeat of CAG bases.
how is phenylketonuria caused?
- recessive inheritance
- mutation is PAH gene (phenylalanine hydroxlase)
if both parents are carriers of PKU, what is the effect on their offspring?
25% will have the disease, 50% will be carriers.
what are the effects of PKU?
- learning disabilities
- behavioural difficulties
- epilepsy
give evidence of interplay between genes and environment in PKU.
genotype will show mutation, but dietary intervention can mean pheotypes appears normal.
describe the difference between monosomy and trisomy.
monosomy has a single copy of chromosomes and spontaneous abortion in early pregnancy, whereas trisomy has three copies of a chromosome and a high rate of spontaneous abortion.
name and describe a disorder caused by chromosomal abnormalities.
downs syndrome:
- trisomy in chromosome 21, overexpression?
- smaller brain size frontal lobes and cerebellum.
- mild-moderate intellectual ability.
- high risk of early onset alzhemiers.
what causes X-linked conditions?
wrong number of chromosomes.
xx are male or female?
female, XY are males.
describe X-inactivation in females.
- switches off one copy of X chromosome during embryogenesis.
- adult female is a mosaic of clones derived from different embryonic cells, within a clone all cells inactivate the same X, but between clones the choice is random.
define Rett syndrome.
- progressive neurodevelopmental disorder almost exclusively affecting females, leading to mental impairment.
- mutation in gene MeCP2, this transcriptional repressor turns off the expression of unwanted genes during synapse formation.
describe fragile X syndrome.
- commonly inherited form of mental retardation
- predominantly males
- mutation in one end of FMR1 gene, consisting of an amplification of CGG repeat (200+ copies)
- FMR1 gene encodes the FMR protein.
define epigenetic and state epigenetic mechanisms.
- inherited change in phenotype
- not due to changes in genotype
- mechanisms: dev, env chemicals, drugs, ageing, diet.
define genomic imprinting.
dev form of epigenetic - gene expression is influenced by other factors.
- some genes are methylated depending on whether they inherited maternally or prenatally.
- imprinting modification is reversible in next generation.
blue genes mean…, red genes mean…
blue - maternally imprinted (paternal genes active)
red - paternal imprinted (maternal genes active)
define chromosomal deletion.
- during meiosis a spontaneous deletion of a part of a chromosome may occur
- if deletion of a paternal chromo only maternal genes present, normal expression of red genes, no expression of blue genes.
- if deletion on maternal chromo only paternal genes present, normal expression of blue genes, no expression of red genes.
deletion on paternal chromosome can cause (prada- willi syndrome/ angelman syndrome)?
prada-willi syndrome - intellectual disability, decreased muscle tone, insatiable appetite.
define angelman syndorme.
- caused by depletion on maternal syndrome, delayed development, language impairment, sociable behaviour.
give evidence that epigenetic modification can be affected by the environment.
maternal care (pup licking) switches on serotonin, action through 5-HT receptor to activate transcription factor NGFIA, which switches on gene (Nr3CI) expressed glucocorticoid receptor (GR).
what are the outcomes of poor maternal care?
- promoter methylated
- low levels of GR
- high anxiety
- high corticosterone levels
- methylation retained through lifetime, without GR loss of feedback in HPA axis (increased stress hormones and anxiety/depression).
define transgenerational epigenetics.
- environmental influences on parents can effect offspring
- disputed histones in sperm cells - showed altered RNA profile in offspring, histones can be modified by chemicals (e.g smoking and drinking).
what do GWAS study?
look for what SNPs sort with disease state.
how is Alzheimers caused?
- mutation in certain genes
- amyloid precursor protein (chromo 12)
- risk identified in gene association or GWAS of late onset AD.
- one SNP difference between APOSES and APOE4.
through conducting twin studies, which disorders and purely genetic and which are polygenic and env?
Huntingtons is purely genetic, schizophrenia and bipolar are polygenetic and effected by the env.
what are the genes found to be involved in schizophrenia associated with?
synaptic transmission , glutamate and dopamine.
name factors that make studying genes difficult.
- defining genetic and non-genetic factors
- understanding interactions among factors
- allowing for individual differences
- limited experimental control and ethical issues in human studies
why are animal studies useful?
- similarity of genes and biological factors with humans
- create inbreed stains of animals that are genetically identical
- control env conditions
- manipulate genes
which animal is the best to study on?
mice - 20 pairs of chromosomes, 99% of mouse genes have homologues in man, suffer from diseases similar to humans, targeted mutagenesis.
state genetic studies using rodents.
- inbreed strains
- BXD recombinant breeding
- genetically engineered mouse models (knockout, knock-in, transgenic mice).
what gene has been found through mice studies to be associated with rest syndrome?
inactive MeCP2 mutation
