Flashcards in Genetics 5, 6, 7 - Modes of inheritance, cancer and clinical practice Deck (33)
What are the 4 non-mendelian modes of inheritance?
MultifactorialiMprinting (epigenetic modification of DNA)MitochondrialMosaicism
What are copy number variations? (CNV)
Extra or missing stretches of DNA
Penetrance of genetics in a mendelian disorder?
Pentrance of genetics in a multifactorial disease?
Genetic change is just another risk factor, therefore penetrance is low for any one mutation
How many genes do monozygotic and dizygotic twins share?
Monozygotic = allDizygotic = 50%
What does P
There is a 1 in 20 probability that the data you see has happened by chance
What are risk models?
Any equation that ties together different risk factors and gives you a risk prediction for your patient
What is epigenetic modification of DNA/ imprinting?
When only one working allele is inherited (either mum or dad allele has been silenced) due to heritable alterations that are not due to changes in DNA sequence. Rather, epigenetic modifications, or tags, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression.
What is DNA methylation?
an epigenetic mechanism that occurs by the addition of a methyl (CH3) group to DNA, thereby often modifying the function of the genes
What is the name for DNA complexed with histones?
Difference between chromosomes, chromatin and chromatids?
Chromatin = double-stranded helical structure of DNANucleosome = DNA complexed with histonesChromataosome = nucleosome + H1 proteinChromosome = tightly coiled nucleososmes - made up of chromatid
Where does methylation of DNA usually occur?
On cytosine bases just before guanine bases
What does DNA methylation cause?
Modification of histones repressing transcription
What is an example of a disease that can occur due to abnormalities of methylation?
Cancer (methylation causes gene silencing - histone de-acetylation is a drug target)
What is an example by how environment affects methylation?
Starvation during pregnancy affects foetus - methylation allows your environment to affect your genome
How can methylation affect behaviour?
RETT syndrome - changes methylation pattern of the genes in brain to the point were certain functions of the brain stop working
What are the symptoms of angelman syndrome?
Neurogenetic disorder causing developmental delay, intellectual disability, ataxia, epilepsy, happy demeanour, frequent laughing and smiling
What causes Angelman's syndrome?
Not having the working copy of the UBE3A gene on chromosome 15It only works in the mother's copy - fathers copy is methylated
What does methyl cytosine mutate easily to?
Apart from in the nucleus, where else is DNA kept in humans?
What is heteroplasmy?
Different daughter cells contain different proportions of mutant mitochondria
What are symptoms of mitochondrial disease?
MyopathyDiabetesDeafnessOptic atrophyStroke like episodesEncephalitis(dependant on mutation type and level of heteroplasty in different tissues)
Are daughters affected more in mitochondria inheritance?
No - sons and daughters are affected equally
What are the 4 ways in which DNA can be damaged?
Inherited mutationsDNA strand breaksMistakes in DNA synthesisChemical damage e.g. UV, smoking
What are the main mechanisms by which genes are activated? (3)
Duplication of the geneActivation of the gene promotorChange in amino acid sequence
What is the fate of a cell that has accumulated DNA damage? (4)
RepairSenescenece (cessation of cell growth of potentially cancerous cells)ApoptosisTumour growth
Mechanisms of DNA repair?
Direct repairBase excisionNucleotide excisionMis-match repair complex
What is mis-match repair?
Mis-mathc e.g. A-C is recognised and excised by mis-mathc repair complex
What is an example of a condition caused by a mutation in a mis-match repair gene?
Hereditary non-polyposis colorectal cancer