Genetics and cancer Flashcards
Where does methylation occur?
CpG islands (5’ end of promoter or exon 1)
Why is histone tail sticking out good?
Other protein modifiers can bind to it.
What types of histone modification happens?
Acetylation (acetyltransferase, alter electric charge, transcription can happen)
Deacetylation: condenses chromatin structure (deactylase)
Methylation: alows binding of repressor protein–heterochromatin
Ubiquitylation, phosphorylation, sumoylation
Where are functional non-coding RNA located?
Introns, between genes, on antisense DNA strand
How does X-inactivation happen?
Transcription and cis-limited spreading of long nc RNA and ncRNA codes the X-chromosomes and inactivates it and meythltransferase binds to X-ist to start the process of methylation
uniparental disomy
Inheritence from only one parent (could be a hole chrosomes or sections)
Imprinting can have an effect:
two active or inactive genes
When can a whole chromosomes UPD happen?
Trisomy rescue; loss of paternal chromosomes
disorganized embryonic structures, no placenta, all maternal gene
ovarian teratoma
all paternal, disorganized placental structures, no fetus
hydatidiform mole of placenta
When can parent-of origin effects have disruption?
UPD, deletion or dup of chromosomes, changes in epigenetic pattern, mut in imprinting control center, altered ncRNA function
Sx: neonatal hypotonia, feeding difficulty, gential hypoplasia, developmental delay, hypopogmentation, distinct face, short
Prader Willi syndrome; paternal chromosome 15 deletion; loss of paternal orgin alleles exp.
Sx: inappropriate laughter, small head, seizures, mental retardation, ataxia gait,
Angelman syndrome; loss of maternal chromsome 15, loss of UBE3A gene exp.
what is nonpenetrance?
failure to manifest even with genotype present; skip generation, could be carriers
Causes of nonpenetrance?
expressed by individual of one sex (heridatoy breast and ovarion cancer)
influenced by modifier genes and polymorphisms (huntington’s disease)
Environmental trigger needed to activate genetic susceptibility (obesity–diabetes and smoking–cancer)
What is variable expressivity? example?
affected individual within same family show diff features (SNPs, copy number)
Neurofibromatosis type 1
anticipation is also a form (mytonic dystrophy and huntington)
When can de novo mut happen?
large genes with repeating motifs, regions of methylated CpG basesm
show up as classical autosomal dominant disease without any one in the family having it,
early lethality or reduced reproductive potential
How does germline mosaicism appear?
New appearance of aut dom diseases, unless second child is affected, otherwise could be de novo, rate is 5-15% depending on disorder
Types of genetic mosaicism
somatic: mut in embryo cell progenitor or mut in adult life (single organ or tissue affected or major cause of adult onset diseases)
Germline: subset of mosacism with germline cells –gonal region: acquired mut and indiv. might not have any overt symptoms.
Allelic heterogeneity
different mut. in the same allele–each family has unique mut.
Locus heterogeneity
mutations in more than one gene: diseases
e.g: hereditory breat/ovarion cancer, fanconi anemia, xeroderma pigmentsosum, lynch syndrom; could involve diff. genes in the same pathway
Clinical heterogeneity
very different phenotypes caused my mut. in the same gene
Variations in recessive phenotype due to?
common allele in population (greather 10% heterozygote frequency); founder populations, level of gene expression, consanguinity
common carrier status may result in
both parents being carriers and resemble a dominant pedigree
Founder effect?
increased prevalence of some genetic mutation in population due to mut being present in small number of founding individuals: mating restriction, bottlenecks of diseases (e.g: Amish, finnish, icelanders)
Gene expression levels affect disease?
allele variants have diff expression levels; expression <50
% causes abnormal functions
what can consanguinity do?
increase of sharing alleles if biallelic state occur
mimic another inheritance pattern (amish/mennonites)
What happens in X-chromsones differences?
different pheno in males vs females, male lethality if nule allele and critical function as well as could be de novo, have mosaicism, and frequently occuring alleles
mitochondrial inheritance?
May resemble X-linked dom, maternal transmission only, heteroplasmy, disease expression by dosage of ab genes within cells
What is disruption in paternal lineage ?
We do not know the father, adoption, pregnancy outside of marriage, need to do forensic analysis of DNA
