Genomics Flashcards
(30 cards)
Definition of:
a) Genomics?
b) Regulatory +/ Functional genomics?
c) Omics?
a) Typically ( always) refers to changes in DNA sequence
b) Typically refers changes in structure, packaging, +
function of DNA sequence + DNA product
c) Describe characterisation + quantification of
biological molecules in an organism
What are 5 autosomal dominant inheritance patterns?
Transmission is vertical
Equal no of male to female affected
Male to male transmission observed
Mutation of one copy of gene necessary to cause disease
Unaffected individuals have unaffected offspring but may arise as new mutation
What are 4 autosomal recessive inheritance patterns?
Mutations in both copies of a gene necessary to cause disease
Both parents are carriers, generally clinically normal
Equal no of affected males and females
Consanguinity may be present
What are 4 X-linked recessive inheritance patterns?
Mutations in 1 copy of a gene necessary cause disease
in males, females would need mutations in both copies of gene
Females with 1 mutated copy of gene normal
Incidence much higher in males than females
No male to male transmission
What is the statistical test, LOD score used for?
Detect presence of linkage
LOD = log10 L(linkage)/L(no linkage)
LOD score >3 consistent mit linkage
What is linkage?
DNA regions located close proximity more likely co-inherited than DNA regions originating from further apart
What 2 factors can confound linkage analysis in single pedigrees?
Non penetrance - appropriate genotype fails to manifest self in phenotype
Phenocopies - phenotype that matches a phenotype caused by genetic factors but individual x have genotype
What is the human exome?
All protein coding regions
What are the 2 types of single nucleotide substitution?
Transition - substitution that conserves base chemistry
Transversion - substitution that changes base chemistry
What is a common type of insertion?
Tandem duplication - inserted material identical to adjacent sequence
What 2 types of DNA variation describe loss of function?
Amorph: variant causes complete loss of gene function
Hypomorph: variant causes partial loss of gene function
What 3 types of DNA variation describe gain of function?
Hypermorph: variant causes increase in normal gene function
Antimorph: dominant alleles that act in opposition to normal gene activity
Neomorphic: variant causes dominant gain of gene function that’s different from normal function
What 3 ways do ‘loss of function’ alleles exhibit a dominant form of inheritance?
Haploinsufficiency - organism v sensitive levels of protein, 50% quantity reduction causes noticeable phenotype
‘Dominant -ve’ effect - formation of homomulteric complexes, protein lose function + disrupts function of normal counterpart
Somatic second hits - organism largely normal, somatic 2nd mutations gives rare clones defective null cells
recessive at cellular levels, dominantly inherited in families
What 2 ways do ‘gain of function’ alleles exhibit a dominant form of inheritance?
Loss of regulation - activity of protein (enzyme etc) loses spatial/temporal specificity, may be due to loss of regulatory region/mislocalization
Novel function - protein has novel effect that x characteristic of normal product
common novel function is formation of insoluble aggregates
What are the 3 rare high risk genes for Alzheimer’s?
APP, PSEN1, PSEN2
What is the definition of penetrance in genetics?
Probability of developing disease
Proportion of carriers who manifest phenotypic signs of condition
What are polygenic risk scores?
Score that predicts an individual’s risk of disease, based on combo of their genotypes + effect size estimates from GWAS results
What is the study of chromosomes called?
Cytogenetics
What does the DNA in mito mostly code for?
Specifics?
Proteins used in oxidative phosphorylation
13 polypeptides
22 transfer RNAs
2 ribosomal RNAs
What are the 2 common mutations in mitochondrial genomes?
Homoplasmy - all copies identical (also refer to position in genome), all copies of genome have same mutation
Heteroplasmy - >1 type of M1 genome present/variation at position, only few genome have mutation
What proteins do nuclear genomes encode?
Proteins prt of oxidative phosphorylation chain
Proteins involved in replication + repair of mitochondrial genome
Proteins that control transcription + processing of mitochondrial genome + in translation
What are 2 features of a mitochondrial disease caused by nuclear genome mutations?
Same inheritance patterns as Mendelian disorders.
Can caused by defects to genes involved in replication, transcription, translation + repair of MT DNA
E.g. Friedreich Ataxia, autosomal recessive
What are 3 features of mitochondrial disease caused by nuclear genome mutations, mit mitochondria dysfunction dependence?
Defects in genes that monitor + regulate mito
Requires mitochondrial dysfunction
Important in ageing
e.g Parkinsons
What are the 2 genes identified with Parkinson’s disease?
What is process?
Parkin + PINK1
Normally PINK1 imported ==> mito, cleaved + released
Damage to MT caused depolarisation of membranes
PINK1 accumulates in outer membrane of MT
Parkin recruited to mitochondria + triggers autophagy
Damage to pathway = build-up of dysfunctional mito
