Genetics 1 Flashcards
Mitochondrial DNA codes for?
tRNA
Oxidative phosphorylation
Next generation sequencing detects?
Nucleotide variations
Most common pathogenic variant?
Missense mutations ( misspell) - Defects build-up in ER
In Silico tools used for detecting missense variant?
Grantham constraint and SIFT (shit) and had CADD (heart attack)
Grantham - amino acid properties
Constraint - conserved gene
SIFT - protein function change
CADD - Harmful effects of SNV
Treatment for missense mutation?
Chemical chaperone (Tegretol, Metformin) = push correct amino acid into place
Treatment for nonsense mutation?
MRNA destroyed by decay protein
so give decay protein inhibitor - cycloheximide
function of topoisomerase enzyme?
unwind DNA histone
what does introns give rise to?
Non-translation RNA ( tRNA, sRNA, mRNA)
Imprinting of allele occurs via?
methylation of gene promoters
Aneuploidy ( abnormal chromosomes sets) caused by?
Chromosome non-disjunction
what RNA involved in protein synthesis? ( translation)
tRNA and rRNA
Regulatory sequences;
Promoter region found where?
Enhancer/silencer region found where?
Promoter - upstream, contain TATA box
Enhancer/Silencer region - anywhere
What are responsible for evolutionary changes?
Variants - alterations to DNA sequences
Dominant and recessive inheritance refers to?
Homozygousity/heterozygousity refers to?
Dominant/recessive = phenotypic trait
Homozygous/heterozygous = genotype
Commonest cause of primary hypogonadism?
Klinefelter syndrome
Most common mode of inheritance?
autosomal dominant
Mosaicism means
Chimerism means?
Mosaicism = 2 or more cell lineage with different genotypes from single zygote ( post-zygote mutation + non-disjunction)
Chimerism = 2 or more cell lineage with different genotypes from different zygotes
Amniocentesis do when?
CVS do when?
Non-invasive prenatal testing do when?
-special about it?
Amniocentesis = 15th week of pregnancy
CVS = 10th week of pregnancy
NPT = 10th weeks onwards - fragments of DNA extracted from maternal blood
-determine sex of foetus, aneuploidy, deletion syndromes
Mitochondrial inheritance - from mother only - why?
Mitochondrial DNA in sperm is in the tail - doesn’t enter egg
No introns!
3 components in gene regulation?
ncRNA (non-coding RNA)
DNA methylation ( CpG promoter region)
-!methylate silences the gene!-
Histone modification - affects chromatin
SNP - single nucleotide polymorphisms - what and where it is located and function?
Non-coding regions - variation nucleotide at specific locus Determines; -susceptibility to disease -response to drugs -genetic linkage markers
What is CRISPR and CAS9
CRISPR - regions of DNA genome that stores genetic information from infecting viruses/bacteria
CAS9 - endonuclease ( scissors) - guided by gRNA to the snip/cut out specific DNA sequence
what does FISH detects?
satellite probing cities
Presence/absence of DNA sequences on chromosome
Localisation locus-specific DNA target
Balanced rearrangements
SNP microarray use to detect what?
google street view
Copy number variations - CNV
Allelic imbalance ( detect 2 copies of allele of same or different )
Uniparental disomy
Chimerism
Long continuous stretches of homozygosity (LCSH)
LCSH ( occurs in consaguinity) usually unmask what?
Recessive disease
Sanger sequencing detects what?
Single gene mutation!
Southern blot vs western blot?
Southern blot - For DNA
DNA fragments chopped up by restriction endonuclease enzyme
Labelled DNA probe added to hybridize area of interest
Western blot - For proteins ( remember HIV proteins)
cells lysed and protein removed
Antibodies to target proteins
MLPA use to detect what?
Microdeletions/duplications that is too small for FISH and Microarray to detect
+
Locus specific
Can detect methylation ( imprinting disorder) in methylation sensitive MLPA
Next generation sequencing detects what?
-Whole genome/exome sequencing
Targeted gene panel testing for what?
NGS : Genetic heterogeneity
Targeted gene panels : multiple groups of genes causing a particular systemic disease
eg. group of genes causing cardiomyopathy
X-linked Recessive Father - key features?
X-linked Dominant Father - key features?
Sons NOT affected
Daughters obligate carriers! - no recombination
Sons NOT affected
Daughters affected!!
what is recurrent mutations?
Specific similar mutations but in different people due to independent event ( not having similar genetic background)
