Genetics Flashcards
Familial risks
What is the incidence of a disorder in relatives compared to the incidence in the general population?
Twin studies
What is the incidence in monozygotic compared to dizygotic twins?
Adoption studies
What is the incidence in adopted children of the disorders which their parent had?
Population and migration studies
What is the incidence in people from a particular ancestry group when they move to a different geographical area?
Huntingdon’s disease
- Autosomal dominant disease with high penetrance
Huntingdon’s features
- Progressive degenerative disorder of the CNS - dementia, movement disorder, personality changes
- Incurable, treatment for symptoms only
- Mutations due to CAG repeat expansion
Huntingdon’s Peak age of onset
40 years
Huntingdon’s transmission
Vertical transmission
Anticipation
Age of onset can decrease with generations
Huntingdon’s aetiology
11 - 34 CAG repeats are normal –> encodes run of 11 - 34 glutamine amino acid residues in the protein
A run of > 35 glutamine residues causes the protein to aggregate in the brain cells –> progressive cell death
>35 CAG repeats in the gene expand further (esp in male meiosis) –> earlier age of onset in children of affected men - anticipation
Toxic-gain-of-function genotype
Penetrance
the chance that a genotype results in the associated phenotype
Hereditary Haemochromatosis
Autosomal recessive condition characterised by iron overload
Hereditary Haemochromatosis aetiology
Due to mutations of HFE gene –> missense mutations, single nucleotide polymorphisms, point mutations
–> change in amino acid - specifying codon
Recessive diseases are usually assoc w/ mutations that cause loss-of-normal-protein function
Hereditary Haemochromatosis Presentation
Life threatening disease associated with high morbidity and mortality
Iron overload –> organ damage
- Regular venesection provides an effective treatment - quantitative reduction in iron stores
Expressivity
Degree to which the range of signs/symptoms for a given trait differ between individuals
Pleitropy
mutations in a single gene can influence multiple phenotypic traits
Polygenic inheritance
the inheritance and expression of a phenotype being determined from many genes at different loci (small additive effects)
Multifactorial disorders
Require interaction of environment and genetic factors to manifest
Proband
1st individual in investigation of related patients with an inherited disorder
The genome
3 million base pairs Packaged in chromosomes ~ 21,000 protein coding genes alternate gene splicing Non-coding RNAs
Tandem repeat
- short sequences of DNA repeated in head to tail fashion
- mini/micro satellites
- variable number of tandem repeats are very polymorphic
Polymorphism
A variant that is common enough to affect more than 1% of chromosomes in a given population
Human Genome Project
1990 - 2003
Mapping variation and functional effects
3 Billion base pairs + 21,000 coding genes
Types of SNV/SNP in coding DNA
Silent mutation
Stop codon
Missense (diff amino acid created)
Pharmacogenetics
Studying individual variants to predict response to medicine or to guide prescribing
Pharmacogenomics
Analysing genome-wide variants in an individual or a population to identify markers that predict response
Meitotic nondisjunction
Failure of tow members of a chromosome pair to separate from one another during meiosis –> both chromosomes go to a single daughter cell
Patau’s Syndreom
Trisomy 13
- Mental retardation, growth failure, low-set ears, deafness, microcephaly, cleft lip and palate, septal defects
Edward’s Syndrome
Trisomy 18
- V. small head, back of head prominent, malformed ears, small mouth and jaw, hands clenched into fists, clubfeet, webbed toes
Down’s Syndrome
Trisomy 21
- Broad, flat face, epicanthic eyefold, short nose, short and broad hands, small and arched pa;ate, growth failure, mental retardation
Turner’s Syndrome
Monosomy X
Short stature, low hair line, webbed neck, constriction of aorta, undeveloped breasts, shield-shaped thorax, elbow deformity
Aneuploidy
when an organism gains/loses a chromosome
–> occurs during meiosis/mitosis, usually non-disjunction
Risk factors for aneuploidy
Increasing maternal age, maternal hypothyroidism, irradiation, viral infection, familial tendency
Splicing mutation
Sequence that guides introns from mRNA are mutated - abnormal splicing.
Translated protein may carry intron sequences –? alterd amino acids incorporated into polypeptide chain
DNA Primary Structure
Chains of nucleotides held by phosphodiester bonds attaching the phosphates
DNA Secondary Structure
2 DNA strands held together by H bonds between complimentary base pairs
DNA Tertiary Structure
Packaging - DNA is wrapped around histones, forming chromatin. Chromatin is packed into nucleosomes and then supercoiled into a chromasome
3 types of RNA in eukaryotic cells
mRNA - messenger
tRNA - transfer
rRNA - ribosomal
Messenger RNA
copied from DNA and used as template for protein synthesis
Transfer RNA
small molecules which transfer amino acids to the ribosomes for protein synthesis
Ribosomal RNA
involved in binding mRNA and tRNA during protein synthesis
In RNA which nitrogen base has changed
thymine –> uracil
