Genetics Exam 4

when RISC-miRNA guide binding is not completely complementary . . . .

translation of mRNA target is repressed

imprinting

epigenetic mechanism in which genes are expressed depending on the parent of origin

what is expressed in imprinting

only one of the alleles (mono-allelic expression) depending on parent of origin (excluded)

prader willi syndrome

deletion of 4 Mb (15q11-q13) of paternal gene

PCR steps

denaturation, hybridization/annealing, extension

denaturation

dsDNA is denatured into single strands

extension

DNA polymerase synthesizes DNA strands

PCR amplification primers

short, single stranded sequences, one complementary to 5' end and the other to 3' end

PCR allows us to . . .

take a very small sample of DNA and amplify it to millions of cells so that the sample becomes large enough for analysis

sometimes even after PCR . . .

DNA is not visualized and has to be reamplified

nucleic acid blotting for proteins

western blot

sequencing

deciphering the code hidden in biological sequences and determine the order of nucleotides/amino acids in DNA/polypeptides

pre-proinsulin

synthesized in pancreas, secreted from cell, amino acids cleaved to make mature insulin molecule containing A/B polypeptide chains

genetic

there's an issue with the genetic material

all cancer is caused by . . .

genetic mutations

majority of cancer cases are from

somatic cells

humans don't pass genetic material from _______________ to offspring

somatic cells

___________________ to cancer can be inherited

predisposition

_________________ itself id not usually inherited

cancer

what causes cancer

genetic predisposition, environmental factors, viruses

viruses that cause cancer

HPV, HBV, EBV

radiations that cause cancer

radon, UV light, x-ray

what DNA damage do xrays cause

phosphodiester bond breaks

what DNA damage does UV light cause

pyrimidine dimers

what DNA damage do alkylating agents cause

transition mutations

what DNA damage do intercalating agents cause

frameshift mutations

what do alkylating agents do

donate an alkyl group to amino or keto groups in nucleotides, altering base pairing affinities, resulting in transition mutations

what do intercalating agents do

wedge between base pairs of DNA and distort DNA duplex, which affect many functions including DNA repair

what does UV light do

modifies DNA nucleotides by encouraging the formulation of additional covalent bonds between adjacent pyrimidine nucleotides, causing the formation of pyrimidine dimers

what do xrays do

are more energetic than UV radiation because they're a type of ionizing radiation, and can cause serious DNA damage like single/double stranded breaks

nearly 50% of all CA involve a missing or damaged _________ gene

p53

what turns a normal cell into an altered cell (dysplasia)

initiation

what turns an altered cell (dysplasia) into a tumor

promotion

what makes a tumor more malignant

promotion

what makes a malignant tumor a metastatic tumor

promotion

what percent of metastatic cells become metastatic tumors

0.01%

metastasis

the special ability of cancer cells to invade other tissues/organs

what do cancer cells do when they invade other tissues/organs

form secondary tumors by extension/separations from original tumor

what does p53 do in normal cells

arrests the cell cycle at G1/S and G2/M checkpoints and retards progression thru S phase, inhibits cyclin/CDK complexes, regulates transcription of other genes involved

what does activated p53 do

instructs damaged cells to commit suicide by apoptosis

what does p53 activate

the transcription of genes whose products control apoptosis

what happens in cancer cells that lack functional p53

gene products are not synthesized and apoptosis doesn't occur

what regulates synthesis/destruction of cyclin proteins

cyclins and cyclin dependent kinases

what can contribute to the development of cancer

mutation of misexpression of any of the genes controlling the cell cycle

two general categories of cancer causing genes

protooncogenes and tumor suppressor cells

protooncogenes

normal cells that regulate cell cycle

mutated/misexpressed protooncogenes cause

gain of function

what do protooncogenes encode

transcription factors that stimulate expression of other genes

what do signal transduction molecules stimulate

cell division

what do cell to cell regulators do

move the cell thru the cell cycle

what do you call a mutated protooncogene

oncogene

what are oncogenes

excessively/inappropriately active versions of a normal protooncogene

mutated or misexpressed tumor suppressor genes cause

loss of function

tumor suppressor genes

code for products that regulate cell cycle checkpoints or initiate the process of apoptosis

what do tumor suppressor genes do in normal cells

half progress thru the cell cycle in response to DNA damage or growth suppression signals

methylation

associated with decreased gene expression

where does methylation occur most often

CpG islands

CpG islands

the cytosine of CG doubled in DNA

how can methylation repress transcription

by binding to transcription factors of DNA

3 major epigenetic mechanisms with a lot of cross talk

DNA methylation, histone modification, microRNAs

what does DNA methylation impact

gene expression

if a promoter is unmethylated . . . .

the gene can be transcribed

if the promoter is methylated . . . .

the gene is silenced

miRNAs

small, noncoding RNAs that contain about 18-22 base pairs

major function of miRNAs

to regulate gene expression

pre miRNAs

exported form nucleus into cytoplasm and then processed to generate miRNA strands

what happens to the mature miRNA

it's incorporated into RISC

RISC

RNS Inducing Silencing Complex that binds to and destroys target mRNAs that have complementary sequences

one miRNA can . . .

target multiple genes and therefore can regulate the production of many proteins

when RISC-miRNA guide pairing is completely complementary . . . .

target mRNA is degraded

when RISC-miRNA guide binding is not completely complementary . . . .

translation of mRNA target is repressed

miRNAs and siRNAs can also associate with . . . .

RITS

RITS

RNA induced transcriptional silencing complex

miRNA/siRNA guides bind to . . .

specific promoters or larger regions of a chromosome

remodeling enzymes are recruited by miRNA/siRNA guides to . . .

convert euchromatin to heterochromatin (transcriptional silence)

imprinting

epigenetic mechanism in which genes are expressed depending on the parent of origin

what is expressed in imprinting

only one of the alleles (mono-allelic expression) depending on parent of origin (excluded)

imprinting patterns are determined during

gamete formation

once a gene is imprinted . . . .

it remains imprinted throughout life

disorders caused by genomic imprinting

prader willi syndrome and angelman syndrome

prader willi syndrome

deletion of 4 Mb (15q11-q13) of paternal gene

angelman syndrome

deletion of 4 Mb (15q11-q13) of maternal gene

quantitative genetics

branch of population genetics which deals with phenotypes which vary continuously (such as height or mass), rather than with phenotypes and gene-products which are discretely identifiable of fixed (such as eye-color, or the presence of a particular biochemical)

most important difference between quantitative and mendelian traits

the number of genes that influence the trait

most traits show more ________________ than single gene disorders

phenotypic variation

quantitative inheritance

continuous variation across a range of phenotypes

types of quantitative inheritance

polygenic and multifactorial traits

polygenic traits

many genes yet each gene has a small effect

what do quantitative traits show in a population

continuum of variation

types of quantitative traits in a population

behavioral traits, multifactorial diseases, physical traits

heritability

estimates the genetic contribution to the variation of the phenotype in a population

high heritability

estimates indicate that much of the population variation is due to genetic variation

low heritability

estimates reflect a larger contribution due to environmental variation

heritability estimates are . . .

population specific and influenced by characteristics of the sample selected

MZ and DZ twins are

concordant (trait expressed by both) or discordant (trait only expressed by one)

PCR steps

denaturation, hybridization/annealing, extension

denaturation

dsDNA is denatured into single strands

hybridization/annealing

primers bind to ssDNA (starting point for DNA polymerase to synthesize new DNA strands)

extension

DNA polymerase synthesizes DNA strands

each PCR cycle results in . . .

amplification