Genetics and cancer

Question 1

Where does methylation occur?

Answer 1

CpG islands (5’ end of promoter or exon 1)

Question 2

Why is histone tail sticking out good?

Answer 2

Other protein modifiers can bind to it.

Question 3

What types of histone modification happens?

Answer 3

Acetylation (acetyltransferase, alter electric charge, transcription can happen)
Deacetylation: condenses chromatin structure (deactylase)
Methylation: alows binding of repressor protein–heterochromatin
Ubiquitylation, phosphorylation, sumoylation

Question 4

Where are functional non-coding RNA located?

Answer 4

Introns, between genes, on antisense DNA strand

Question 5

How does X-inactivation happen?

Answer 5

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

Question 6

uniparental disomy

Answer 6

Inheritence from only one parent (could be a hole chrosomes or sections)
Imprinting can have an effect:
two active or inactive genes

Question 7

When can a whole chromosomes UPD happen?

Answer 7

Trisomy rescue; loss of paternal chromosomes

Question 8

disorganized embryonic structures, no placenta, all maternal gene

Answer 8

ovarian teratoma

Question 9

all paternal, disorganized placental structures, no fetus

Answer 9

hydatidiform mole of placenta

Question 10

When can parent-of origin effects have disruption?

Answer 10

UPD, deletion or dup of chromosomes, changes in epigenetic pattern, mut in imprinting control center, altered ncRNA function

Question 11

Sx: neonatal hypotonia, feeding difficulty, gential hypoplasia, developmental delay, hypopogmentation, distinct face, short

Answer 11

Prader Willi syndrome; paternal chromosome 15 deletion; loss of paternal orgin alleles exp.

Question 12

Sx: inappropriate laughter, small head, seizures, mental retardation, ataxia gait,

Answer 12

Angelman syndrome; loss of maternal chromsome 15, loss of UBE3A gene exp.

Question 13

what is nonpenetrance?

Answer 13

failure to manifest even with genotype present; skip generation, could be carriers

Question 14

Causes of nonpenetrance?

Answer 14

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)

Question 15

What is variable expressivity? example?

Answer 15

affected individual within same family show diff features (SNPs, copy number)
Neurofibromatosis type 1
anticipation is also a form (mytonic dystrophy and huntington)

Question 16

When can de novo mut happen?

Answer 16

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

Question 17

How does germline mosaicism appear?

Answer 17

New appearance of aut dom diseases, unless second child is affected, otherwise could be de novo, rate is 5-15% depending on disorder

Question 18

Types of genetic mosaicism

Answer 18

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.

Question 19

Allelic heterogeneity

Answer 19

different mut. in the same allele–each family has unique mut.

Question 20

Locus heterogeneity

Answer 20

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

Question 21

Clinical heterogeneity

Answer 21

very different phenotypes caused my mut. in the same gene

Question 22

Variations in recessive phenotype due to?

Answer 22

common allele in population (greather 10% heterozygote frequency); founder populations, level of gene expression, consanguinity

Question 23

common carrier status may result in

Answer 23

both parents being carriers and resemble a dominant pedigree

Question 24

Founder effect?

Answer 24

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)

Question 25

Gene expression levels affect disease?

Answer 25

allele variants have diff expression levels; expression <50

% causes abnormal functions

Question 26

what can consanguinity do?

Answer 26

increase of sharing alleles if biallelic state occur

mimic another inheritance pattern (amish/mennonites)

Question 27

What happens in X-chromsones differences?

Answer 27

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

Question 28

mitochondrial inheritance?

Answer 28

May resemble X-linked dom, maternal transmission only, heteroplasmy, disease expression by dosage of ab genes within cells

Question 29

What is disruption in paternal lineage ?

Answer 29

We do not know the father, adoption, pregnancy outside of marriage, need to do forensic analysis of DNA