1.1 Genetics

Question 1

human genes

Answer 1

25,000 - less than twice as many as a worm –> alternative splicing?

Question 2

percentage of shared genome btw 2 people

Answer 2

99.50%

Question 3

the 0.5% of difference in humans indicates

Answer 3

polymorphisms, muations - 15million base pairs

Question 4

most common polymorphism

Answer 4

SNP - single nucleotide polymorphism –> 6 x 10^6 are known

Question 5

SNPs are usually biallelic meaning

Answer 5

only 2 choices at a given site withing the population

Question 6

Are SNPs mutations?

Answer 6

NO - they do not totally remove activity

Question 7

less than 1% of SNPs occur in

Answer 7

coding regions meaning that most will have to undergo linkage analysis that may prove to be significant

Question 8

linkage disequilibirum

Answer 8

bc less than 1% of SNPs occur in coding cregions, SNPs are most often co-inherited as a marker linked to a gene causing disease

Question 9

CNPs

Answer 9

copy number variations - can be bi-allelic or multipel - 50% involve gene coding sequences, genes involved in immune system and CNS over represented in containing CNPs, much less is known about CNPs and disease susceptibility than SNPs

Question 10

when you see an SNP in 90% of a disease population

Answer 10

that is significant information bc you can look to see if that SNP is linked with a gene that causes the disease

Question 11

genetics

Answer 11

study of single genes

Question 12

genomics

Answer 12

study of entire genome and interactions

Question 13

how do you use DNA chips

Answer 13

can use them to study tumor vs normal tissue or stimualted cells vs control cell

Question 14

Proteonomics

Answer 14

study of all of the proteins in a tissue/cell 2d electrophoresis/mass spec. or isotope coding affinity tags (heavy and light isotopes and mass spec) –>not every thing that transcribed is translated into protein so studying proteins is very important

Question 15

laser capture microdissection

Answer 15

if you have a tumor, remember it is normal to have vessles and stromal tissue so you used this micordisection to just cut out the tumor cells

Question 16

microarrays

Answer 16

you can do a blind scree just by hybridizing dna testing for thousands of genes, looking at diseased vs no disease – then you can go and look at the genes and make a hypothesis

Question 17

with microarrayes the colors mean something

Answer 17

red - tumor dna, green- normal dna, yellow -mixed dna

Question 18

functional cloning - classical approach

Answer 18

gene product and defect are known - you clone the normal gene, make probes, clone and sequence the gene from affected individuals (many metabolic disorders)–find a way to fix it

Question 19

positional cloning - candidate gene approach

Answer 19

gene is not known - uses cytogenetic or SNP marker to localize candidate genes to a narrow area of a chromosome, clone DNA from that area express normal and disease products – find out what’s wrong

Question 20

cloning and the production of ultra pure proteins examples

Answer 20

insuline, factor 8, soluble TNF receptor, humanized antibodies

Question 21

gene therapy is complex because

Answer 21

cannot anticipate for all factor – SCIDS (gamma cahin of cytokine receptor) gene inserted next to host gene regulating cell growth _. Gave the patient T-cell leukemia

Question 22

how insuline was adjusted

Answer 22

first we made insuline from pigs, but we were making reactive Ab against the pig inuline so we made human insuline, but if it wasn_t refridgerated it would not be effective and pts were not getting their full dose, so now things are added to it to make it heat stable

Question 23

With rhematoid arthritis why is giving the Abs to TNF bad

Answer 23

the Abs will clear the TNF so that is good to reduce inflammation, but if you have TB and you need to wall it off you need TNF to maintain the granuloma and if you don’t then you can’t maintain it — so you need to make sure that the person doesn’t have TB or that they are vaccinated to make sure anti-TNF treatment is appropriate (also given in Psoriasis)

Question 24

sickle cell treatment

Answer 24

could be treated by giving normal Hg cells but its not a thrapy

Question 25

Anti amyilid Ab in alzhimers

Answer 25

if animal is immunized with Ab towards tau that causes plaques alzheimers can be reversed, but in humans if immunized with the Ab they got inflammatory encephalitis and some people die

Question 26

RNA analysis

Answer 26

many alteration in DNA are single gene effects so copy number is low. mRNA has higher copy number if gene is transcribed. Many genes are rearranged (BCR-ABL) over larger areas than PCR can replicate, but looking for the mRNA that is formed after splicing and cutting is easier.

Question 27

Epigenetic effects include

Answer 27

DNA methylation, histone acetylation, miRNAs --> we know genetic alterations in DNA seq cannot explain the diversity of human phenotypes such as phenotypic difference in monzygotic twins -- so we look at epigenetc changes

Question 28

too much miRNA and cancer

Answer 28

too much scilencing of tumor suppressor genes can lead to cancer

Question 29

too little miRNA and cancer

Answer 29

too little scilencing of oncogenes can lead to cancer

Question 30

Congenital

Answer 30

means present at birth. If you are starved for air during birth and you have massive CNS problems it is congenital NOT genetic. Congenital diseases may or may not be genetic.

Question 31

Familial

Answer 31

multifactorial diseases that run in families but show no inheritance patterns

Question 32

Hereditary

Answer 32

gene passed down

Question 33

Genetic

Answer 33

involves genes

Question 34

Prevalence of chromosomal abnormalities

Answer 34

50% of spontaneous abortions contain a chromosomal abnormaility--the earlier the abortion, the more likely a chromosomal abnormality. 1% of live births have an identifiable chromosomal abnormalitiy. Chromosomal abnormalities visible, other mutations are not. 5% of individuals less than 25 develop a disease with a significant genetic component --but these are not chormosomal

Question 35

interplay of genetics and environment

Answer 35

the most common diseases afflicting man have goth genetic and environmentla components (diabetes, atherosclerotic heart disease, cancer, obesity)

Question 36

which diabetes has a stronger genetic component

Answer 36

type 2 but also has a strong environmental compoent like obesity

Question 37

genes and environment leading to disease

Answer 37

lots of genetic w/ few environmental factors, lots of environmental with few genetic factors, or lots of genetic and environmental factors will lead to diseas --- usually one genetic and one environmental factor is not going to lead to disease

Question 38

point mutations

Answer 38

occur bc the DNA code is degenerate -- missence, nonsense, promoter activation/inactivation

Question 39

missense

Answer 39

AA substitution, full lenth protein made, variable preservation of structure and function

Question 40

Nonsense mutation

Answer 40

AA change introducing a stop codon

Question 41

Point mutations in Sicle cell

Answer 41

DNA: CTC to CAC , RNA: GAG to GUG, AA: Glutamic acid to Valine

Question 42

deletions or additions result in

Answer 42

fame shifts

Question 43

examples of triple expansion repeats

Answer 43

Huntington, Fragile X, ---- mostly repeating CG sequences

Question 44

What kind of mutations are more common?

Answer 44

loss of function bc it is easier to destroy something than give it an alternative fn. altered gene product that affects other proteins (dominant negative), gain ro altered function (rarer, Huntington disease)

Question 45

Mendelian Disorders

Answer 45

single gene alterations, predictable inheritance pattern, Pleiotrophism (single gene with multiple effects - Marfans), Heterogenetity (multiple genes same effect: profound deafness)

Question 46

Patterns of inheritance

Answer 46

autosomal dominant, autosomal recessive, x-linked, multifactorial

Question 47

What form do you see disease in AD cases

Answer 47

Heterozygotes -- homozygotes are usually fatal

Question 48

Children of one affected AD parent

Answer 48

have 50% cance of developing the disease

Question 49

Autosomal Dominant and new mutations

Answer 49

some patients do not have an affected parent --new mutations account for variable percentages of cases. Usually older males increase the incicence of mutations in sperm -- 30% of marfan's is denovo

Question 50

Penetrance

Answer 50

percentage of individuals with the gene that have the disease -- we only consider penetrance with autosomal dominant cases

Question 51

Variable expression

Answer 51

all individuals have the disease but different severity or character